Antiphospholipid syndrome, complicated by small bowel necrosis – case report

Catedra chirurgie generală, USMF „N.Testemițanu”, Chișinău, Moldova, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Sindromul antifosfolipidic (SAFL) reprezintă o dereglare autoimună a coagularii, care conduce la tromboza intravasculara și deseori este asociată cu complicațiile sarcinii. Foarte puține cazuri de ischemie mezenterică clinic evidentă în cadrul SAFL sunt raportate pînă în prezent. Material și metode: În Clinica chirurgie generală cu dureri abdominale severe a fost internată o pacientă în virsta de 29 de ani, în perioada de lăuzie - 22 zile după întreruperea spontană a sarcinii. Laparoscopia diagnostică și laparotomia ulterioară au evidențiat prezența necrozei unei anse a intestinului subțire, situate aproximativ la un metru de la ligamentul Treitz. S-a efectuat rezecția ansei afectate cu anastomoza termino-terminală. Evoluția postoperatorie a fost favorabilă. Rezultate: Diagnosticul SAFL a fost stabilit și confirmat în baza istoricului bolii (4 sarcini întrerupte), analizelor de laborator (trombocitopenie), reacției imunoenzimatice (nivelul elevat de anticorpi anti-cardiolipinici și anti-fosfolipidici), CT-arteriografiei abdominale (tromboza venelor porta, lienala și mezenterica superioară), examenului histologic al piesei operatorii (tromboza venoasă și arteriala a mezoului ansei intestinale rezecate). Pacientei i s-a administrat tratament anticoagulant profilactic: aspirina și warfarina, menținîndu-se nivelul INR-ului: 2,0-3,0. Concluzii: La pacienții cu tromboza mezenterială inexplicabilă este importantă examinarea nivelului de anticorpi anti-cardiolipinici și anti-fosfolipidici pentru stabilirea diagnosticului de SAFL și administrarea tratamentului anticoagulant de prevenire a complicațiilor.Background: Antiphospholipid syndrome (APLS) is an autoimmune disorder of coagulation, which lead to intravascular thrombosis and often is associated with the complications of pregnancy. Cases of clinically evident mesenteric ischemia within APLS are very rare reported. Material and methods: In Department of General Surgery with severe abdominal pain was admitted a woman aged 29 years, 22 days after spontaneous discontinuation of pregnancy. Diagnostic laparoscopy and subsequent laparotomy revealed the presence of necrotic small bowel loop, located approximately at one meter from the Treitz ligament. Resection of affected loop with termino-terminal anastomosis was performed. Postoperative evolution was uneventful. Results: The diagnosis of APLS was established and confirmed on the basis of history (4 pregnancies interrupted), laboratory tests (thrombocytopenia), enzyme-linked immunosorbent assay (elevated levels of anti-cardiolipin and anti-phospholipid antibodies), abdominal CT-arteriography (thrombosis of portal, splenic and superior mesenteric veins), histological examination of the operative specimen (venous and arterial thrombosis of resected bowel loop mesentery). To the patient was prescribed a prophylactic anticoagulant treatment: aspirin and warfarin, maintaining the INR: 2.0-3.0. Conclusions: Study of the anti-cardiolipin and anti-phospholipid antibodies level is important in patients with unexplained mesenteric thrombosis in order to diagnose the APLS and to administrate the anticoagulant therapy to prevent complications

Allosteric Modulation of Binding Specificity by Alternative Packing of Protein Cores.

Hydrophobic cores are often viewed as tightly packed and rigid, but they do show some plasticity and could thus be attractive targets for protein design. Here we explored the role of different functional pressures on the core packing and ligand recognition of the SH3 domain from human Fyn tyrosine kinase. We randomized the hydrophobic core and used phage display to select variants that bound to each of three distinct ligands. The three evolved groups showed remarkable differences in core composition, illustrating the effect of different selective pressures on the core. Changes in the core did not significantly alter protein stability, but were linked closely to changes in binding affinity and specificity. Structural analysis and molecular dynamics simulations revealed the structural basis for altered specificity. The evolved domains had significantly reduced core volumes, which in turn induced increased backbone flexibility. These motions were propagated from the core to the binding surface and induced significant conformational changes. These results show that alternative core packing and consequent allosteric modulation of binding interfaces could be used to engineer proteins with novel functions