Search

Although endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) presents a delicate alternative treatment for abdominal aortic aneurysms (AAA) with lower perioperative mortality, its long-term efficacy remains a matter of concern. The purpose of this study was to evaluate the currently reported mortality evidence after EVAR and to examine the possible effect of aneurysm status and the study period on mortality rates. The PubMed and Cochrane bibliographical databases were thoroughly searched for studies reporting on more than 1 000 patients with non-ruptured or ruptured infrarenal AAA, treated with EVAR from August 1991 to September 2016. A total of 10 910 titles/abstracts were retrieved and 121 studies were deemed relevant. Twenty-six studies met the inclusion criteria and reported on 354 500 patients with a mean age of 74.6 years. Almost all of the studies referred to elective EVAR and the mean aneurysm size was 5.58 cm. The most common early complication for elective EVAR was perioperative bleeding (1.9 %), whereas hospital-acquired pneumonia was a major concern in urgent EVAR (28.5 %). Conversion rate to open surgery was 1.2 %. The 30-day all-cause mortality rate was 4.84 % (1.7 % for non- ruptured aneurysms, 33.8 % for ruptured aneurysms).The overall all-cause late mortality in a mean follow-up period of 23.8 months was 19.1 %. The aneurysm-related late mortality rate was 3.4 %. With respect to the time period of patient enrollment, studies reporting on patients recruited before 2006 were found to face more secondary complications and higher late mortality rates than patients enrolled after 2005.The endovascular treatment of large and anatomically suitable infrarenal AAA in selected patients remains a safe alternative to open repair. Our findings demonstrate that newer studies show better long-term outcomes than the older ones, proposing a possible improvement of EVAR techniques and perioperative care and providing encouraging evidence for a wider application of EVAR. © 2018 Hogrefe.

The p75 neurotrophin receptor (p75NTR) is a death domain (DD) containing receptor of the TNF/FAS(APO-1) family. p75NTR has recently been shown to mediate apoptosis in certain types of neurons as well as in oligodendrocytes. The molecular mechanisms by which p75NTR stimulates apoptosis are still unknown. Here, we have tested whether overexpression of p75NTR could modulate survival of sympathetic neurons cultured in the presence or absence of NGF. Moreover, using the yeast two-hybrid system, we tested whether p75NTR intracellular domain was able to dimerize or interact with known DD-containing proteins including FADD, RIP, RAIDD and TRADD. We found that over-expression of p75NTR had no effect on the survival of sympathetic neurons cultured in the presence of NGF but instead delayed neuronal death following NGF deprivation. These results strongly support the finding that p75NTR is not involved in the apoptosis process induced by NGF deprivation in sympathetic neurons. We also foun d that the intracellular domain of p75NTR failed to associate either with itself or with other known DD-containing proteins. This suggests that the mechanisms by which p75NTR triggers apoptosis in certain cell types are different from those used by other receptors of the TNF/FAS family.

Sympathetic neurons undergo programmed cell death (PCD) upon deprivation of nerve growth factor (NGF). PCD of neurons is blocked by inhibitors of the interleukin-1beta converting enzyme (ICE)/Ced-3-like cysteine protease, indicating involvement of this class of proteases in the cell death programme. Here we demonstrate that the proteolytic activities of the proteasome are also essential in PCD of neurons. Nanomolar concentrations of several proteasome inhibitors, including the highly selective inhibitor lactacystin, not only prolonged survival of NGF-deprived neurons but also prevented processing of poly(ADP-ribose) polymerase which is known to be cleaved by an ICE/Ced-3 family member during PCD. These results demonstrate that the proteasome is a key regulator of neuronal PCD and that, within this process, it is involved upstream of proteases of the ICE/Ced-3 family. This order of events was confirmed in macrophages where lactacystin inhibited the proteolytic activation of precursor ICE and the subsequent generation of active interleukin-1beta.

The p53 tumour suppressor gene plays a major role in controlling cell cycle and apoptosis in many different cell types. Here we have examined the status and the potential apoptosis inducing activity of p53 in sympathetic neurons. The p53 protein is expressed in rat sympathetic neurons cultured in the presence of NGF. The protein is not upregulated when these neurons are induced to die upon NGF deprivation. Over-expression of wild-type human p53 in neurons cultured in the presence of NGF does not trigger apoptosis nor does it accelerate apoptosis when the neurons are deprived of NGF. Finally endogenous p53 expression is not necessary for neuronal cell death triggered by NGF deprivation since neurons prepared from p53 knockout mice undergo normal cell death upon NGF deprivation. Our results suggest that p53 may have an unknown function in post-mitotic neurons which is distinct from its well described roles in apoptosis or cell cycle control.

The p75 neurotrophin receptor (p75NTR) is a death domain (DD) containing receptor of the TNF/FAS(APO-1) family. p75NTR has recently been shown to mediate apoptosis in certain types of neurons as well as in oligodendrocytes. The molecular mechanisms by which p75NTR stimulates apoptosis are still unknown. Here, we have tested whether overexpression of p75NTR could modulate survival of sympathetic neurons cultured in the presence or absence of NGF. Moreover, using the yeast two-hybrid system, we tested whether p75NTR intracellular domain was able to dimerize or interact with known DD-containing proteins including FADD, RIP, RAIDD and TRADD. We found that over-expression of p75NTR had no effect on the survival of sympathetic neurons cultured in the presence of NGF but instead delayed neuronal death following NGF deprivation. These results strongly support the finding that p75NTR is not involved in the apoptosis process induced by NGF deprivation in sympathetic neurons. We also foun d that the intracellular domain of p75NTR failed to associate either with itself or with other known DD-containing proteins. This suggests that the mechanisms by which p75NTR triggers apoptosis in certain cell types are different from those used by other receptors of the TNF/FAS family.

The p53 tumour suppressor gene plays a major role in controlling cell cycle and apoptosis in many different cell types. Here we have examined the status and the potential apoptosis inducing activity of p53 in sympathetic neurons. The p53 protein is expressed in rat sympathetic neurons cultured in the presence of NGF. The protein is not upregulated when these neurons are induced to die upon NGF deprivation. Over-expression of wild-type human p53 in neurons cultured in the presence of NGF does not trigger apoptosis nor does it accelerate apoptosis when the neurons are deprived of NGF. Finally endogenous p53 expression is not necessary for neuronal cell death triggered by NGF deprivation since neurons prepared from p53 knockout mice undergo normal cell death upon NGF deprivation. Our results suggest that p53 may have an unknown function in post-mitotic neurons which is distinct from its well described roles in apoptosis or cell cycle control.

The promoter regions of human choline acetyltransferase (ChAT) and aromatic L-amino acid decarboxylase (AADC) genes have been analyzed by transient transfection assays. AADC gene is transcribed from two alternative noncoding first exons, 1N and 1NN, expressed in pheochomocytoma and hepatoma cells, respectively. 5' flanking sequences of exon 1 N (from 9000 to 147 bp) display promoter activity in SK-N-BE neuroblastoma cells, but not in MC-I-XC cholinergic neuroepithelioma cells, and in AADC-rich non-neuronal cells. On the contrary, 5' flanking sequences of exon 1 NN (from 1117 to 119 bp) display high promoter activity in human hepatoma cells HepG2, but not in SK-N-BE cells, suggesting high degrees of specificity of promoters N and NN for AADC-expressing neuronal and non-neuronal cells, respectively. Preliminary evidence suggests that leukemia inhibitory factor suppresses the activity of the neuronal promoter in cultured sympathetic neurons. Two alternative first exons, R and M, have been localized in human ChAT gene, and the corresponding promoters characterized in cholinergic PC12 and NG-108-15 cells, and in non-cholinergic neuro2A cells. Several positively or negatively acting cis elements have been localized in the two promoters, as well as a cAMP-inducible, enhancer-like element in the second intron. Among the various cell lines studied, there was no correlation between promoter activities and the expression of the endogenous ChAT gene, suggesting that the fine-tuning of ChAT gene expression is controlled by silencer elements which remain to be localized.