An unusual case of dysphagia after endovascular exclusion of thoracoabdominal aortic aneurysm

Purpose: To report an unusual case of dysphagia that developed immediately after stent-grafting of a thoracoabdominal aortic aneurysm. Case Report: A 79-year-old woman was submitted to a staged hybrid repair of a thoracoabdominal aortic aneurysm and developed new onset dysphagia and regurgitation early after stent-grafting of the thoracic aorta. Esophageal imaging showed a marked endoluminal stenosis, suggesting the development of secondary achalasia. The patient was submitted to endoscopic injections of botulinum toxin at the lower esophageal sphincter, which completely resolved the symptoms. Conclusion: Acute dysphagic syndrome after thoracic aorta endografting has been anecdotically reported, and its etiology remains undefined. In this report, we illustrate the clinical features of this rare condition, discuss etiological hypotheses, and suggest a noninvasive therapeutic approach. © 2009 by the International Society of Endovascular Specialists

Studio multicentrico prospettico sulla resistenza agli azoli in ceppi di aspergillus isolati da tamponi di sorveglianza effettuati in pazienti ematologici e/o sottoposti a trapianto di cellule staminali ematopoietiche (Studio Arte)

L\u2019aspergillosi invasiva (AI) \ue8 una complicanza severa in pazienti ematologici ed in pazienti sottoposti a trapianto di cellule staminali ematopoietiche (HSCT). In questi pazienti la diagnosi si basa principalmente su metodi indiretti (galattomannano) per la difficolt\ue0 di ottenere campioni biologici con metodiche invasive, ma questo comporta la mancanza del ceppo fungino responsabile dell\u2019infezione. La colonizzazione delle vie aeree superiori rappresenta il primo passo nello sviluppo dell'infezione polmonare ed \ue8 stato dimostrato che le colture di sorveglianza delle secrezioni nasali ed orofaringee hanno un elevato valore predittivo positivo. La multi-azolo resistenza di Aspergillus fumigatus \ue8 stata riscontrata anche in Italia sia in ceppi isolati dall'ambiente che in ceppi clinici da pazienti in terapia antifungina e na\uefve. Alla base della resistenza vi sono mutazioni puntiformi di CYP51A, gene che codifica per l'enzima bersaglio di azoli. Lo studio multicentrico prospettico ARTE ha avuto come obiettivi: 1) raccogliere, dai diversi centri partecipanti, i ceppi di Aspergillus isolati da tamponi di sorveglianza di pazienti ematologici o sottoposti a HSCT; 2) analizzare la sensibilit\ue0 in vitro agli azoli (itraconazolo, voriconazolo e posaconazolo); 3) indagare, in presenza di resistenza, il meccanismo molecolare; 4) correlare la resistenza alle variabili demografiche e comportamentali ed agli eventuali trattamenti antifungini. Ventidue centri di ematologia di 11 regioni italiane hanno aderito al progetto ARTE. Tra il 2015 ed il 2016 sono stati raccolti 292 ceppi da 228 pazienti (et\ue0 media 55 anni; maschi 60%; il 41.6% viveva in campagna). Le specie pi\uf9 frequentemente isolate sono state: A. fumigatus (46.9%), A. niger (21.9%), A. flavus (16.1%), A. terreus (4.4%), A. nidulans (1.7%). Tre isolati sono risultati resistenti agli azoli: un ceppo di A. fumigatus (itraconazolo MIC 4 mg/L e posaconazolo MIC 0.5 mg/L), un ceppo di A. niger (itraconazolo MIC >16 mg/L) ed uno di A. lentulus (itraconazole MIC >16 mg/L). A. lentulus e A. niger sono noti in letteratura per avere valori di sensibilit\ue0 elevati agli azoli (in particolare ad itraconazolo). Il ceppo di A. fumigatus resistente \ue8 stato isolato da un paziente affetto da mieloma che aveva subito un autotrapianto di cellule staminali ematopoietiche, con antigene galattomannano positivo su lavaggio broncoalveolare con un quadro radiologico compatibile e che, inoltre, viveva in campagna ed era un fumatore. Tale ceppo aveva la mutazione TR34/L98H nel gene CYP51A e, dall\u2019analisi dei microsatelliti (MLST), \ue8 risultato differente dai ceppi ambientali ed altri ceppi clinici della stessa area geografica con i quali \ue8 stato confrontato. Il presente studio ha fatto emergere alcune problematiche gi\ue0 riscontrate in questi tipi di sorveglianze. La mancanza di protocolli comuni per le colture di sorveglianza nelle cliniche ematologiche e nei laboratori ha portato ad avere un numero molto diverso di campioni tra i centri partecipanti. Inoltre la difficolt\ue0 di ottenere, nei pazienti ematologici, le colture fungine, che rappresentano il principale strumento diagnostico, porta sicuramente ad una sottostima sia della colonizzazione/infezione sia della resistenza. Dato che pazienti con AI causata da un ceppo resistente hanno un tasso di mortalit\ue0 dell'88% vs il 30-50% dei pazienti con ceppo sensibile, il poter isolare precocemente il fungo responsabile potrebbe essere determinante per l\u2019outcome del paziente

Gq-16, a novel peroxisome proliferator-activated receptor γ (pparγ) ligand, promotes insulin sensitization without weight gain

The recent discovery that peroxisome proliferator-activated receptor γ (PPARγ) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPARγ activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPARγ. The structure of GQ-16 bound to PPARγ demonstrates that the compound utilizes a binding mode distinct from other reported PPARγ ligands, although it does share some structural features with other partial agonists, such as MRL-24 and PA-082, that have similarly been reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium exchange studies reveal that GQ-16 strongly stabilizes the β-sheet region of the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5-mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that the partial agonist activity of GQ-16 results from the compound's weak ability to stabilize helix 12 in its active conformation. Our results suggest that the emerging model, whereby "ideal" PPARγ-based therapeutics stabilize the β-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PPARγ modulators that retain antidiabetic actions while minimizing untoward effects. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.The recent discovery that peroxisome proliferator-activated receptor γ (PPARγ) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPARγ activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPARγ. The structure of GQ-16 bound to PPARγ demonstrates that the compound utilizes a binding mode distinct from other reported PPARγ ligands, although it does share some structural features with other partial agonists, such as MRL-24 and PA-082, that have similarly been reported to dissociate insulin sensitization from weight gain. Hydrogen/deuterium exchange studies reveal that GQ-16 strongly stabilizes the β-sheet region of the receptor, presumably explaining the compound's efficacy in inhibiting Cdk5-mediated phosphorylation of Ser-273. Molecular dynamics simulations suggest that the partial agonist activity of GQ-16 results from the compound's weak ability to stabilize helix 12 in its active conformation. Our results suggest that the emerging model, whereby "ideal" PPARγ-based therapeutics stabilize the β-sheet/Ser-273 region and inhibit Cdk5-mediated phosphorylation while minimally invoking adipogenesis and classical agonism, is indeed a valid framework to develop improved PPARγ modulators that retain antidiabetic actions while minimizing untoward effects28733281692817

Nematóides do Brasil. Parte V: nematóides de mamíferos Brazillan nematodes. Part V: nematodes of mammals

<abstract language="eng">A survey of nematode species parasitizing Brazilian mammals is presented, with enough data to provide their specific identification. The tirst section refers to the survey ofthe species, related to 21 superfamilies, 45 families, 160 genera and 495 species that are illustrated and measurement tables are given. The second section is concerned to the catalogue ofhost mammals which includes 34 families, 176 species and their respective parasite nematodes. The identification of these helminths is achieved by means of keys to the superfamilies, families and genera. Specific determination is induced through the figures and tables as above mentioned