SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes

Background

Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.

Results

Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.

Conclusion

This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat

     

Subarachnoid hemorrhage due to cerebral aneurysmal rupture during pregnancy

Cerebral aneurysmal complications rarely occur during pregnancy. Telling the difference between eclampsia and cerebral hemorrhage due to aneurysmal rupture can prove to be difficult. Aneurysmal management should be performed in an emergency but fetal prognosis should be considered. We report a series of eight pregnant women presenting aneurysmal complications and we have assessed their management and outcome. Both maternal and perinatal mortality rates were correlated with the maternal clinical score. We stress the role of combined care by both neurosurgeons and obstetricians. An emergency cesarean section followed by aneurysmal treatment appears to be a widely accepted strategy in pregnant women with cerebral aneurysmal complications.     

Abnormal placentation and selective embolization of the uterine arteries

OBJECTIVE: Abnormal placentation accounts for more than 50% of uterine artery embolization failure. The authors report their experience in this situation. STUDY DESIGN: Seven women presented with abnormal placentation. Uterine artery embolization was carried out in emergency or prophylactic control of postpartum bleeding. RESULTS: In five patients, control of postpartum hemorrhage was obtained without hysterectomy. In two cases with no placental removal and prophylactic procedures, hysterectomy and blood transfusion were not necessary. The manual removal of the placenta was achieved secondarily, respectively on the 25th and the 12th day. CONCLUSIONS: The success rate of uterine artery embolization for postpartum bleeding appears to be lower with abnormal placentation. In none of the cases with the placenta present was it possible to leave the residual placenta in place. However, embolization may permit a safe waiting period and spontaneous migration of the placenta. When the diagnosis is made before delivery, prophylactic uterine artery embolization without placental removal should be considered to reduce blood transfusion and preserve fertility.     

Limits to arterial embolization treatment of severe postpartum hemorrhage

OBJECTIVE: To assess the limits of arterial embolization in the management of serious postpartum haemorrhage (PPH). STUDY DESIGN: Retrospective study. PATIENTS AND METHODS: We examined the cases of 29 patients admitted to intensive care units of Rouen University Hospital for PPH between January 1994 and August 1999. Demographic, obstetrical and biological data, the required treatment and eventual side effects were collected and analysed using the appropriate parametric and non parametric tests. RESULTS: Arterial embolization was carried out on 15 patients (52%) with a success rate of 73%. Of the 14 other patients, 11 underwent conservative or radical surgery without further complications, three received medical treatment. No maternal death occurred; however, one patient transferred from a local hospital and already presenting haemodynamic instability suffered cardiac arrest before embolization. Arterial embolization was unsuccessful in four cases, two of which were cases of placenta accreta. These patients were older (p < 0.05) and all had a past history of curettage and/or caesarean section for preceding deliveries (p < 0.01). CONCLUSIONS: Emergency arterial embolization is a valuable therapy in case of PPH but can only be carried out in specialised units. Obstetrical antecedents would appear to constitute a major risk factor and transfer increases the morbidity rate.     

Small for gestational age infant in association with maternal prothrombin gene variant (nt 20210A).

Most of disproportionate infants born small for gestational age (SGA) have an history of placental dysfunction with no explained cause. We report a case of an unexplained SGA infant with placental infarctions and thrombosis. Maternal thrombophilic disorder tests revealed that the patient was heterozygous for the A20210 prothrombin gene variant a newly identified thrombotic risk factor. It may be suggest that prothrombin gene variant, as factor V Leiden, could be a genetic risk factor for placental insufficiency.     

Waldmann disease and pregnancy

Waldman disease, also called intestinal lymphangiectasis, is a protein-loosing enteropathy caused by anomalous intestinal lymphatic canals. The condition is transmitted by autosomal dominant inheritance. Diet therapy including medium chain triglycerides improves the disease course. The condition occurs in early childhood. We report a case observed in a pregnant woman with intestinal lymphangiectasis. She delivered a full-term infant and experienced no major complications.     

Plasma progesterone kinetics following surgical treatment of ectopic pregnancies.

OBJECTIVES: Comparative study of plasma progesterone and betaHCG kinetics following surgical treatment of ectopic pregnancy. STUDY DESIGN: Prospective study involving 62 patients with tubal ectopic pregnancies. Study of the kinetics of plasma progesterone and betaHCG, and the correlation coefficient between plasma progesterone and betaHCG levels during post-operative follow-up. RESULTS: Thirty-nine patients were treated by salpingostomy and 23 by salpingectomy. Analyzing the betaHCG kinetics according to treatment revealed that both curves were convergent on day 2. Progesterone kinetics differed greatly in that they appeared "parallel and confused". Analyzing the correlation between betaHCG and progesterone levels proved the absence of a significant link. CONCLUSIONS: Studying the kinetics of plasma progesterone after surgical treatment of ectopic pregnancies revealed a fast decrease in progesterone. Statistical analysis of the progesterone concentration showed that post-operative kinetics is fully independent from that of betaHCG. Progesterone therefore cannot be substituted to betaHCG for post-operative follow-up.