Conditions of endoplasmic reticulum stress favor the accumulation of cytosolic prion protein.

After signal sequence-dependent targeting to the endoplasmic reticulum (ER), prion protein (PrP) undergoes several post-translational modifications, including glycosylation, disulfide bond formation, and the addition of a glycosylphosphatidylinositol anchor. As a result, multiple isoforms are generated. Because of the intrinsic weakness of the PrP signal sequence, a fraction of newly synthesized molecules fails to translocate and localizes to the cytosol. The physiopathologic role of this cytosolic isoform is still being debated. Here we have shown that, in both cultured cell lines and primary neurons, ER stress conditions weaken PrP co-translational translocation, favoring accumulation of aggregation-prone cytosolic species, which retain the signal sequence but lack N-glycans and disulfides. Inhibition of proteasomes further increases the levels of cytosolic PrP. Overexpression of spliced XBP1 facilitates ER translocation, suggesting that downstream elements of the Ire1-XBP1 pathway are involved in PrP targeting. These studies reveal a link between ER stress and the formation of cytosolic PrP isoforms potentially endowed with novel signaling or cytotoxic functions

The family Caecidae (Gastropoda: Caenogastropoda) in Argentine waters

This is the first formal report of members of the family Caecidae in Argentine waters. Caecum striatum de Folin, 1868, C. strigosum de Folin, 1868, and C. achirona (de Folin, 1867) are re-described from shallow waters off Piedras Coloradas ( 4053.0810 S, 6507.5920 W), Rı´o Negro Province, Argentina. This is the farthest south record of these species which were previously recorded from USA, Bahamas, Panama, Brazil, and Uruguay. The authors also make observations about the different ontogenetic stages of the studied species. Scanning electron microscope illustrations of radula and operculum are provided for the first time.Fil: Pastorino, Roberto Santiago Guido. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Chiesa, Ignacio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

A systematic review of infected descending thoracic aortic grafts and endografts

Objective: The objective of this study was to collect and critically analyze the current evidence on the modalities and results of treatment of descending thoracic aortic surgical graft (SG) and endograft (EG) infection, which represents a rare but dramatic complication after both surgical and endovascular aortic repair. Methods: A comprehensive electronic health database search (PubMed/MEDLINE, Scopus, Google Scholar, and the Cochrane Library) identified all articles that were published up to October 2017 reporting on thoracic aortic SG or EG infection. Observational studies, multicenter reports, single-center series and case reports, case-control studies, and guidelines were considered eligible if reporting specific results of treatment of descending thoracic aortic SG or EG infection. Comparisons of patients presenting with SG or EG infection and between invasive and conservative treatment were performed. Odds ratio (OR) meta-analyses were run when comparative data were available. Results: Forty-three studies reporting on 233 patients with infected SG (49) or EG (184) were included. Four were multicenter studies including 107 patients, all with EG infection, associated with a fistula in 91% of cases, with a reported overall survival at 2 years of 16% to 39%. The remaining 39 single-center studies included 49 patients with SG infection and 77 with EG infection. Association with aortoesophageal fistula was significantly more common with EG (60% vs 31%; P = .01). In addition, time interval from index procedure to infection was significantly shorter with EG (17 +/- 21 months vs 32 +/- 61 months; P = .03). Meta-analysis showed a trend of increased 1-year mortality in patients with SG infection compared with EG infection (pooled OR, 3.6; 95% confidence interval, 0.9-14.7; P = .073). Surgical management with infected graft explantation was associated with a trend toward lower 1-year mortality compared with graft preservation (pooled OR, 0.3; 95% confidence interval, 0.1-1.0; P = .056). Conclusions: Thoracic aortic EG infection is likely to occur more frequently in association with aortoesophageal fistulas and in a shorter time compared with SG infection. Survival is poor in both groups, especially in patients with SG infection. Surgical treatment with graft explantation seems to be the preferable choice in fit patients

Hybrid repair of an aortic arch aneurysm with complex anatomy: Right aortic arch and anomalous origin of supra-aortic vessels

We performed a one-stage hybrid surgical and endovascular procedure to manage a 6.5-cm right aortic arch aneurysm associated with anomalous origin of the supra-aortic vessels in a 70-year-old man. Complete surgical rerouting of the supra-aortic vessels was followed by the endovascular repair of the right aortic arch aneurysm with a Zenith TX2 stent graft (Cook, Bloomington, Ind) and Z-track plus introducer system. The procedure was successfully completed with exclusion of the aortic arch aneurysm, and the patient was discharged on postoperative day 7. Aortic arch aneurysms with complex anatomy may be successfully treated with a less invasive hybrid approach using new generation devices

Pericardial Fat Pad and Thoracic Aortic Surgery

Pericardial fat pads have been successfully used for many years by thoracic and cardiac surgeons for a number of applications. We recently used a pedicled and well-vascularized pericardial fat pad in a patient who underwent replacement of a distal aortic arch aneurysm with a Dacron tube graft, in order to avoid contact between the anastomoses and the oesophagus in an effort to reduce the risk of subsequent infection and fistula formation. This simple technique may provide a source of vital tissue that may be useful for protecting anastomoses after thoracic aortic surgery, particularly in cases requiring re-operation. To our knowledge the use of pericardial fat pads has not been previously reported in the English literature for this purpose Pericardial fat pads have been successfully used for many years by thoracic and cardiac surgeons for a number of applications. We recently used a pedicled and well-vascularized pericardial fat pad in a patient who underwent replacement of a distal aortic arch aneurysm with a Dacron tube graft, in order to avoid contact between the anastomoses and the oesophagus in an effort to reduce the risk of subsequent infection and fistula formation. This simple technique may provide a source of vital tissue that may be useful for protecting anastomoses after thoracic aortic surgery, particularly in cases requiring re-operation. To our knowledge the use of pericardial fat pads has not been previously reported in the English literature for this purpose. © 2003 Elsevier Science Ltd. All rights reserved

Intraoperative stenting of the internal carotid artery after unsuccessful eversion endarterectomy

AbstractStenting Of The Internal Carotid Artery (ICA) Has Been Shown To Be Feasible In Atherosclerotic Lesions, In Restenosis After Carotid Endarterectomy, And In Spontaneous Carotid Dissections. To Correct An Intimal Flap That Detached Distal Occlusion Of The Ica After Eversion Carotid Endarterectomy, As Shown With Intraoperative Completion Angiography, We Successfully Used Stenting Of The Ica With A Self-EXPANDABLE Stainless Steel Stent Placed During Surgery Through The Common Carotid Artery. (J Vasc Surg 1999;30:355-6.

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

PrP Sc , a misfolded, aggregation-prone isoform of the cellular prion protein (PrP C ), is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals. PrP Sc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, posing challenges for the development of effective therapies. Since PrP C is the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity, it represents an attractive therapeutic target for prion diseases. In this minireview, we briefly outline the approaches to target PrP C and discuss our recent identification of Zn(II)-BnPyP, a PrP C -targeting porphyrin with an unprecedented bimodal mechanism of action. We argue that in-depth understanding of the molecular mechanism by which Zn(II)-BnPyP targets PrP C may lead toward the development of a new class of dual mechanism anti-prion compounds