Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis.

In vasculitis disorders, inflammation affects blood vessels. Granulomatosis with polyangiitis (GPA) is a chronic systemic vasculitis distinguished by the presence of anti-proteinase-3 autoantibodies (anti-PR3). In this study we analyzed the molecular signature of human umbilical endothelial cells (HUVECs) in response to neutrophil-derived extracellular vesicles (EVs). EVs were obtained from anti-PR3-activated neutrophils, purified and characterized by flow cytometry, nanoparticle tracking and miRNA screening. HUVECs were stimulated with EVs and miRNA/mRNA expression was measured. Cell culture media proteins were identified by antibody microarrays and selected cytokines were measured. Comparison of differentially expressed miRNAs/mRNAs between non-stimulated and EV-stimulated HUVECs revealed two regulatory patterns. Significant up-regulation of 14 mRNA transcripts (including CXCL8, DKK1, IL1RL1, ANGPT-2, THBS1 and VCAM-1) was accompanied by 11 miRNAs silencing (including miR-661, miR-664a-3p, miR-377-3p, miR-30d-5p). Significant down-regulation was observed for nine mRNA transcripts (including FASLG, CASP8, STAT3, GATA3, IRAK1 and IL6) and accompanied by up-regulation of 10 miRNAs (including miR-223-3p, miR-142-3p, miR-211-5p). Stimulated HUVECs released IL-8, Dickkopf-related protein 1 (DKK-1), soluble interleukin (IL)-1 like receptor-1 (ST2), growth differentiation factor 15 (GDF-15), angiopoietin-2, endoglin, thrombospondin-1 and vascular adhesion molecule-1 (VCAM-1). Moreover, transfection of HUVECs with mimics of highly expressed in EVs miR-223-3p or miR-142-3p, stimulated production of IL-8, ST2 and endoglin. Cytokines released by HUVECs were also elevated in blood of patients with GPA. The most increased were IL-8, DKK-1, ST2, angiopoietin-2 and IL-33. In-vitro stimulation of HUVECs by neutrophil-derived EVs recapitulates contribution of endothelium in autoimmune vasculitis. Proinflammatory phenotype of released cytokines corresponds with the regulatory network of miRNAs/mRNAs comprising both EVs miRNA and endothelial cell transcripts.

[Intrahepatic portocaval shunt as a new method for treating and prevention of bleeding from esophageal varices in portal hypertension]. / Wewnatrzwatrobowe zespolenie wrotno-systemowe jako nowa metoda w leczeniu i zapobieganiu krwotokom z zylaków przelyku w nadcisnieniu wrotnym.

UNLABELLED: The aim of this study was the presentation of percutaneous transjugular intrahepatic porto-systemic shunt (TIPS) and its place among the other methods of the treatment of esophageal variceal bleedings. In the period from June 1992 to December 1997, 31 cirrhotic patients with portal hypertension and recurrent variceal bleedings were submitted for TIPS. This group consisted of 14 female and 17 male patients, their age ranging from 17 to 68 years (average 52). According to Child-Pugh classification 4 patients represented group A, 11--group B and 16--group C. Each of these patient was admitted to our Department after recurrent bleeding, resistant to typical treatment: terlipressein infusion, balloon tamponade and endoscopic sclerotherapy. In 24 patients (78%) TIPS was performed successfully. In 7 cases TIPS was performed in candidates for orthotopic liver transplantation. CONCLUSIONS: TIPS is quite new, nearly 10 years old method for portal decompression. It is an effective and less invasive method than surgical procedures in the treatment of portal hypertension, especially in Child-Pugh group B and C patients if the sclerotherapy is not effective. It protects cirrhotic patients waiting for liver transplantation against the esophageal bleedings.

[TIPS in treatment of patients with recurrent bleeding from esophageal varices]. / TIPS w leczeniu chorych z nawracajacymi krwotokami z zylaków przelyku.

In the period from January 1992 to May 1997 we performed 20 procedures of percutaneous transjugular intrahepatic porto-systemic shunt (TIPS) in the patients with liver cirrhosis and recurrent variceal bleedings. This group consisted of 10 male and 10 female patients, their age ranging from 17 to 68 years (average 52). The etiology of cirrhosis was alcoholic in 8 cases, postinflammatory in 6, primary biliary in 4 and autoimmunological in 2 cases. According to Child-Pugh classification 4 patients represented group A, 10-group B and 6-group C. Each of these patient was admitted to our Department after recurrent bleeding, resistant to typical treatment: vasopressin infusion, balloon tamponade and endoscopic sclerotherapy. In 3 cases TIPS was performed in candidates for orthotopic liver transplantation.

Congenital calcification of the larynx and trachea.

The fifth case of diffuse laryngeal and tracheal cartilage calcification in infancy is reported. The previously reported cases are briefly described. Differential diagnosis and potential etiologies are discussed. It is thought that these patients represent a rare but distinct clinical entity.