Cíl práce: Zhodnotit první zkušenosti s endovaskulární léčbou AAA bifurkačními stentgrafty Ella (Ella - CS, Hradec Králové, Česká republika) s cílem optimalizovat konstrukci bifurkačního stentgraftu, zaváděcího systému a techniku implantace. Materiál a metodika: Od září 1996 do října 1997 jsme ve FN v Olomouci léčili celkem 10 nemocných s vydutí abdominální aorty endovaskulárně bifurkačním stentgraftem Ella. Jednalo se o 9 mužů a 1 ženu, ve věku od 50 do 75 let, s průměrem 62,5 roku. Výsledky: Úspěšně jsme vyřadili AAA z oběhu u 8 nemocných. Netěsnost jedné z anastomóz, která vedla ke zpětnému toku krve do vaku vyduté ("endoleak") jsme zaznamenali u 2 nemocných. Celková průměrná doba sledování byla 6,2 měsíce. Závěr: Bifurkační stentgraft Ella je indikovaný v léčbě vydutí subrenální aorty zasahujících k bifurkaci nebo přesahujících přes bifurkaci až na pánevní tepny. Námi používaný zaváděcí systém je jednoduchý, práce s ním je spolehlivá a bezpečná. Krátkodobé výsledky na relativně malém souboru jsou slibné.
Objective: Evaluate initial experience with endovascular treatment of AAA by an Ella bifurcated stentgraft (Ella - CS, Hradec Králové, Czech Republic) with the aim to optimalize the construction of the bifurcated stentgraft, the introducer delivery system and technique of implantation. Material and methods: From September 1996 till October 1997 the authors treated in the University Hospital Olomouc a total of 10 patients with aneurysms of the abdominal aorta by an endovascular bifurcated stentgraft Ella. The group comprised 9 men and one woman, age 50 - 75 years, mean age 62.5 years. Results: The AAA was successfully eliminated from the circulation in 8 patients. Leaking from one anastomosis which led to reversed blood ilow into the aneurysmal sac ("endoleak") was recorded in two patients. The mean total follow up period was 6.2 months. Conclusion: A bifurcated Ella stentgraft is indicated in the treatment of aneurysms of the subrenal aorta reaching as far as the bifurcation or extending beyond the bifurcation to the pelvic artery. The introducer delivery system used by the authors is simple, reliable and safe. Short-term results assembled in a relatively small group are promising.
Cíl: Zhodnocení čtyřletých výsledků léčby aneuryzmatu abdominální aorty (AAA) stentgraftem Ella Z hlediska bezpečnosti a efektivity léčby ve vztahu k morfologii výdutě. Materiál a metodika: Ze skupiny 103 pacientů s AAA, u kterých byla zvažována endovaskulární léčba, bylo 70 nemocných (68 %) indikováno k tomuto druhu terapie. Bifurkační typ stentgraftu byl implantován 54 nemocným, uniiliakální typ dvanácti nemocným. Pouze čtyri nemocni byli vhodní pro implantaci tubámího typu stentgraftu. Každému z pacientů byla před propuštěním provedena kontrolní angiografie. CT a dopplerovské tdtrasonografické (US) kontroly byly prováděny 3,6 a 12 měsíců po implantaci stentgraftu a dále pak každých 12 měsíců. Výsledky: Primární technické úspěšnosti bylo dosaženo u 61 z celkem 70 nemocných (87,1 %). Primárni endoleak byl zaznamenán u 9 nemocných; proximální perigraft endoleak u 5 nemocných, distální u 3 a intersegmentální u 1 nemocného. Endoleak spontánně vymizel u jednoho nemocného. sekundárni endovaskulámí intervence včetně endovaskulámí konverze byla provedena u 4 nemocných, U dvou pacientů byl proximální perigraft endoleak řešen chirurgicky bandingem proximálního krčku. To vedlo k sekundární technické úspěšnosti 97,1 %. Chirurgická konverze byla indikována u 2 pacientů (2,9 %). Průměrná doba sledování byla 17,2 měsíce (od 3 do 49 měsíců). V průběhu s] sledování byl u 8 nemocných (11,4 %) při kontrolním CT nebo doplerovské US zaznamenán sekundámi endoleak, jedenkrát došlo k parciální trombóze stentgraftu. Závěr: Léčba AAA stentgraftem Ella je účinná a bezpečná. Bifurkační stentgraft je nejčastěji používaným typem stentgraftu. Uniiliakální typ je používán pouze u nemocných s komplikovanou morfologií subrenální aorty a pánevního řečiště. Tubami typ stentgraftu je indikován jen velmi zřídka.
Objective: Evaluation of four-year results of AAA treatment by Ella stent grafts with regard to safety and effectivity in relation to morphology of the aneurysm. Materials and methods: From a group of 103 patients with AAA, where endovascular treatment was considered, 70 of them (68 %) were found to be suitable for this type of therapy. The bifurcated type of stentgraft was implanted in 54 patients, the uniiliacal type in 12 patients and only 4 patients were suitable for the tubular type of stent graft. Control angiography was performed immediately before discharge. CT and US controls were performed 3,6 and 12 months after implantation, later every 12 months. Results: Primary technical success was achieved in 61 of the 70 patients (87.1 %). Primary endoleak was recorded in 9 patients; proximal perigraft endoleak in 5 patients, intersegmental in 1 and distal perigraft endoleak in 3. Endoleak spontaneously disappeared in 1 patient, secondary endovascular intervention, including endovascular conversion, was performed in 4 patients, in two patients surgical banding of the proximal neck was performed. Secondary technical success was 97.1 %. Surgical conversion was indicated in 2 patients (2.9 %). Total average follow-up period was 17.2 months (3 - 49 months). In 8 patients (11.4 %) secondary endoleak was found on CT or US control, in one patient partial thrombosis of the stent graft was found. Conclusion: Treatment of AAA with the Ella stent graft system is effective and safe. Bifurcated stent graft is the most frequently used type. The uniiliacal type of stent graft is used by ourselves only in cases of complicated morphology. The tubular type of stent graft is rarely indicated.
- MeSH
- Aortic Aneurysm, Abdominal classification MeSH
- Angioplasty, Balloon MeSH
- Humans MeSH
- Stents MeSH
- Check Tag
- Humans MeSH
- MeSH
- Aortic Aneurysm, Abdominal surgery complications mortality MeSH
- Blood Vessel Prosthesis Implantation MeSH
- Humans MeSH
- Aortic Rupture surgery classification mortality MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Comparative Study MeSH
Úvod: Ischémia čreva po operáciách AAA je zriedkavou komplikáciou. Je ale najčastejšou príčinou smrti po operáciách AAA. Incidencia je 5–9 % a 30–60 % pri RAAA s mortalitou až 60 %. Metodika: Retrospektívne sme vyhodnotili súbor pacientov operovaných pre AAA v období 1. 1. 2007 až 31. 7. 2010. Sledovali sme klinické, paraklinické príznaky a prejavy, ktoré viedli k diagnóze. Zaznamenali sme výsledky operačnej liečby a príčinu úmrtia pacientov. Výsledky: V uvedenom období sme operovali 207 pacientov s AAA. 174 (84 %) bolo operovaných elektívne, 33 (16 %) akútne. V pooperačnom období zomreli 19 pacienti (9,2 %). Najčastejšou príčinou úmrtia bola ischemická kolitída – 8 pacienti (42 %). IK sme diagnostikovali u 17 pacientov (8,2 %) s mortalitou 41,2 %. Diagnóza bola stanovená kolonoskopicky u 58,8 %, ostatných pacientov sme operovali na základe známok NPB. V skupine pacientov s včasnou diagnózou a liečbou IK, t.j. do 4 pooperačného dňa, bola mortalita 20 %, ale stúpla na 71,4 %, ak bola diagnóza stanovená neskôr. Diskusia: Vznik ischemickej kolitídy sa nedá v pooperačnom období nikdy vylúčiť, preto treba po nej aktívne pátrať, hlavne u pacientov s rizikovými faktormi. Klinické známky sú nešpecifické, najčastejšie je to rýchly nástup peristaltiky a krvavé, profúzne hnačky. Z biochemických markerov sú sľubné prokalcitonín a D-laktát. Metódou voľby je kolonoskópia, ktorú treba zrealizovať pri každom nejasnom pooperačnom priebehu. O nutnosti operačnej revízie rozhodne nielen kolonoskopický nález, ale významnou mierou aj klinický obraz a celkový stav pacienta. Chirurgická liečba spočíva v resekcii nekrotického čreva a výkon je vždy ukončený stómiou. Záver: Diagnostika IK je obtiažna a rozhodnutie o reoperácii napriek klinickým a paraklinickým vyšetreniam ostáva na chirurgovi a jeho chirurgickej skúsenosti. Len včasná a adekvátna liečba má nádej na úspech, oddialenie diagnózy zväčša vedie k fatálnemu koncu.
Introduction: Bowel ischemia following the AAA operation is a rare complication. However, it is the most common reason of death after elective AAA operation with the incidence of 5–9% and 30–60% following RAAA operation with mortality rate around 60%. Methods: Retrospective analysis of 207 patients undergoing elective and emergent AAA operation between 1st January 2007 and 31st July 2010 was made. We evaluated clinical and para clinical symptoms leading to the observed diagnosis. Results: During the observed period we have treated 207 patients with the AAA. 174 (84%) patients were elective, 33 (16%) were urgent (RAAA). Postoperative mortality of the entire group was 19 patients (9.2%). The most common reason of death was found to be ischemic colitis – 8 patients (42%). Ischemic colitis was diagnosed in 17 patients (8.2%) with the mortality 41.2%. Diagnosis was made by colonoscopy in 58.8% of patients, the rest was operated on following the clinical finding of an acute abdomen. In a group of patients with an early diagnosis and treatment of ischemic colitis (until the 4th post operative day) the mortality rate was 20%, increasing till 71.4% when the diagnosis was done later than on 4th postoperative day. Discussion: Nevertheless the ischemic colitis is a rare complication following AAA operation the surgeon must be proactive regarding this severe complication especially in high risk patients. Clinical symptoms are not specific, most often too early peristaltic and diarrhoea with addition of blood is apparent. Procalcitonine and D-lactate seem to be promising among the blood markers. Colonoscopy is a method of choice if there is any doubt in postoperative process. The need of relaparotomy is given by colonoscopy finding together with clinical, biochemical symptoms, signs and the clinical status of the patient. The resection of diseased part of bowel with the colostomy is mandatory. Conclusion: The final diagnosis of ischemic colitis is difficult and the decision for reoperation is a matter of surgeons’ experience despite of clinical and paraclinical findings. Only fast and adequate treatment can be successful. Any delay in diagnosis is fatal for the patients.
Reptin is a member of the AAA+ superfamily whose members can exist in equilibrium between monomeric apo forms and ligand bound hexamers. Inter-subunit protein-protein interfaces that stabilize Reptin in its oligomeric state are not well-defined. A self-peptide binding assay identified a protein-peptide interface mapping to an inter-subunit "rim" of the hexamer bridged by Tyrosine-340. A Y340A mutation reduced ADP-dependent oligomer formation using a gel filtration assay, suggesting that Y340 forms a dominant oligomer stabilizing side chain. The monomeric ReptinY340A mutant protein exhibited increased activity to its partner protein AGR2 in an ELISA assay, further suggesting that hexamer formation can preclude certain protein interactions. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) demonstrated that the Y340A mutation attenuated deuterium suppression of Reptin in this motif in the presence of ligand. By contrast, the tyrosine motif of Reptin interacts with a shallower pocket in the hetero-oligomeric structure containing Pontin and HDX-MS revealed no obvious role of the Y340 side chain in stabilizing the Reptin-Pontin oligomer. Molecular dynamic simulations (MDS) rationalized how the Y340A mutation impacts upon a normally stabilizing inter-subunit amino acid contact. MDS also revealed how the D299N mutation can, by contrast, remove oligomer de-stabilizing contacts. These data suggest that the Reptin interactome can be regulated by a ligand dependent equilibrium between monomeric and hexameric forms through a hydrophobic inter-subunit protein-protein interaction motif bridged by Tyrosine-340. SIGNIFICANCE: Discovering dynamic protein-protein interactions is a fundamental aim of research in the life sciences. An emerging view of protein-protein interactions in higher eukaryotes is that they are driven by small linear polypeptide sequences; the linear motif. We report on the use of linear-peptide motif screens to discover a relatively high affinity peptide-protein interaction for the AAA+ and pro-oncogenic protein Reptin. This peptide interaction site was shown to form a 'hot-spot' protein-protein interaction site, and validated to be important for ligand-induced oligomerization of the Reptin protein. These biochemical data provide a foundation to understand how single point mutations in Reptin can impact on its oligomerization and protein-protein interaction landscape.
- MeSH
- AAA Domain * MeSH
- ATPases Associated with Diverse Cellular Activities chemistry metabolism MeSH
- DNA Helicases chemistry metabolism MeSH
- Protein Interaction Domains and Motifs physiology MeSH
- Humans MeSH
- Molecular Chaperones chemistry metabolism MeSH
- Protein Multimerization * MeSH
- Mutation MeSH
- Molecular Dynamics Simulation MeSH
- Carrier Proteins chemistry metabolism MeSH
- Tyrosine genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Aortic Aneurysm, Abdominal surgery MeSH
- Angioplasty methods statistics & numerical data trends MeSH
- Surgical Procedures, Operative methods statistics & numerical data trends MeSH
- Humans MeSH
- Postoperative Complications surgery MeSH
- Risk MeSH
- Stents statistics & numerical data trends MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
- MeSH
- Acute Disease surgery MeSH
- Aortic Aneurysm surgery classification MeSH
- Humans MeSH
- Graft Survival MeSH
- Stents MeSH
- Check Tag
- Humans MeSH
elektronický časopis
- MeSH
- Hearing Disorders MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- otorinolaryngologie
- NML Publication type
- elektronické časopisy
Mitochondrial protein quality control is crucial for the maintenance of correct mitochondrial homeostasis. It is ensured by several specific mitochondrial proteases located across the various mitochondrial subcompartments. Here, we focused on characterization of functional overlap and cooperativity of proteolytic subunits AFG3L2 (AFG3 Like Matrix AAA Peptidase Subunit 2) and YME1L (YME1 like ATPase) of mitochondrial inner membrane AAA (ATPases Associated with diverse cellular Activities) complexes in the maintenance of mitochondrial structure and respiratory chain integrity. We demonstrate that loss of AFG3L2 and YME1L, both alone and in combination, results in diminished cell proliferation, fragmentation of mitochondrial reticulum, altered cristae morphogenesis, and defective respiratory chain biogenesis. The double AFG3L2/YME1L knockdown cells showed marked upregulation of OPA1 protein forms, with the most prominent increase in short OPA1 (optic atrophy 1). Loss of either protease led to marked elevation in OMA1 (OMA1 zinc metallopeptidase) (60 kDa) and severe reduction in the SPG7 (paraplegin) subunit of the m-AAA complex. Loss of the YME1L subunit led to an increased Drp1 level in mitochondrial fractions. While loss of YME1L impaired biogenesis and function of complex I, knockdown of AFG3L2 mainly affected the assembly and function of complex IV. Our results suggest cooperative and partly redundant functions of AFG3L2 and YME1L in the maintenance of mitochondrial structure and respiratory chain biogenesis and stress the importance of correct proteostasis for mitochondrial integrity.
- MeSH
- ATPases Associated with Diverse Cellular Activities genetics metabolism MeSH
- HEK293 Cells MeSH
- Humans MeSH
- Metalloendopeptidases genetics metabolism MeSH
- Mitochondrial Membranes metabolism MeSH
- Mitochondrial Proteins genetics metabolism MeSH
- Mitochondria metabolism ultrastructure MeSH
- Cell Proliferation genetics physiology MeSH
- ATP-Dependent Proteases genetics metabolism MeSH
- Microscopy, Electron, Transmission MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
