Postoperative extracorporeal life support in pediatric cardiac surgery: recent results

We retrospectively reviewed the files of 19 extracorporeal life support (ECLS) applications performed after cardiac surgery in 15 patients from January 2002 to December 2004. We placed 16 arteriovenous ECLS applications with oxygenator, 2 venovenous ECLS applications with oxygenator, and 1 biventricular ECLS application without oxygenator (graft dysfunction after heart transplant). Mean age was 4.9 +/- 7 years (median 5.9 months, range 11 days to 21 years). All patients underwent surgery for congenital heart disease, except for one patient who had a heart transplant. Indications were hemodynamic failure in 12 cases, respiratory failure in 5 cases, and mixed failure in 2 cases. Four patients were undergoing cardiopulmonary resuscitation during ECLS placement (no deaths). Mean delay between surgery and ECLS placement was 3.2 +/- 3.4 days (median 2 days). Mean ECLS duration was 3.4 +/- 5.8 days (mean 6 days, range 3-16 days). Three patients had further surgery for residual lesions. Thirteen patients (86.7%) survived to ECLS weaning; 12 patients survived to hospital discharge (80%). No survivor presented obvious neurologic damage. Specific morbidity included reentry for bleeding, multiple transfusions, and mediastinitis. These results support early placement of ECLS in children whenever a severe postoperative hemodynamic or respiratory failure, refractory to medical treatment, is present.     

Complement C5 in experimental autoimmune encephalomyelitis (EAE) facilitates remyelination and prevents gliosis

Activation of the classical complement system is known to play a central role in autoimmune demyelination. We have analyzed the role of complement component C5 in experimental autoimmune encephalomyelitis (EAE) using C5-deficient (C5-d) and C5-sufficient (C5-s) mice. Both groups of mice displayed early onset EAE, a short recovery phase, and similar stable chronic courses. However, in contrast to the clinical similarities, marked differences were apparent by histopathology. During acute EAE in C5-d, a delay in inflammatory cell infiltration and tissue damage was observed along with restricted lesion areas, which in C5-s mice were more extensive and diffuse. More striking were the differences in chronic lesions. In C5-d mice, inflammatory demyelination and Wallerian degeneration were followed by axonal depletion and severe gliosis, while in C5-s, the same initial signs were followed by axonal sparing and extensive remyelination. In C5-d, immunohistochemistry and Western blotting showed an increase in glial fibrillary acidic protein and a decrease in neurofilament protein, proteolipid protein, and several pro-inflammatory markers. These results in the EAE model indicate that absence of C5 resulted in fiber loss and extensive scarring, whereas presence of C5-favored axonal survival and more efficient remyelination.     

Overexpression of RGC-32 in colon cancer and other tumors

Tumors often exhibit deregulation of the cell cycle and overexpression of cyclins and cyclin-dependent kinases (CDKs). Response gene to complement (RGC)-32 is a substrate and regulator of CDC2 and its overexpression induces cell cycle activation. We investigated RGC-32 mRNA and protein expression in tumors with special emphasis in colon carcinoma. By using an expression array technique we found that 19% of tumor tissues showed increased RGC-32 mRNA expression over the levels of corresponding normal tissues. On the other hand, an increased RGC-32 protein was found in 70% of colon adenocarcinoma samples tested. In colon carcinomas, two major patterns of RGC-32 immunoreactivity were seen: staining of malignant epithelial cells only in some tumors and RGC-32 reactivity of both malignant epithelia as well as cells in the interstitium in others. Colonic epithelium obtained from normal individuals was consistently negative for RGC-32 protein. Overexpression of RGC-32 protein was found in other tumors including prostate, bladder, breast, lung, and other digestive tract tumors. RGC-32 expression was present in the same malignant epithelial cells that also expressed the proliferation marker Ki-67. Our data suggest that RGC-32 overexpression might be part of the deregulation of the cell cycle that is required for the growth of tumor cells.     

Differentiation of stem cells into insulin‐producing cells under the influence of nanostructural polyoxometalates

Two polyoxometalates (POMs) with W were synthesized by a two‐step, self‐assembling method. They were used for stimulation of mesenchymal stem cell differentiation into insulin‐producing cells. The nanocompounds (tris(vanadyl)‐substituted tungsto‐antimonate(III) anions [POM1] and tris‐butyltin‐21‐tungsto‐9‐antimonate(III) anions [POM2]) were characterized by analytical techniques, including ultraviolet‐visible, Fourier transform infrared, nuclear magnetic resonance spectroscopy, and transmission electron microscopy. We found that these polyoxotungstates, with 2–4 nm diameters, did not present toxic effects at the tested concentrations. In vitro, POM1 stimulated differentiation of a greater number of dithizone‐positive cells (also organized in clusters) than the second nanocompound (POM2). Based on our in vitro studies, we have concluded that both the POMs tested had significant biological activity acting as active stimuli for differentiation of stem cells into insulin‐producing cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Assessment of Gene Expression Profiles in Peripheral Occlusive Arterial Disease

Background

Molecular events responsible for the onset and progression of peripheral occlusive arterial disease (POAD) are incompletely understood. Gene expression profiling may point out relevant features of the disease.

Methods

Tissue samples were collected as operatory waste from a total of 36 patients with (n = 18) and without (n = 18) POAD. The tissues were histologically evaluated, and the patients with POAD were classified according to Leriche-Fontaine (LF) classification: 11% with stage IIB, 22% with stage III, and 67% with stage IV. Total RNA was isolated from all samples and hybridized onto Agilent 4×44K Oligo microarray slides. The bioinformatic analysis identified genes differentially expressed between control and pathologic tissues. Ten genes with a fold change ≥ 2 (1 with a fold change ≥ 1.8) were selected for quantitative polymerase chain reaction validation (GPC3, CFD, GDF10, ITLN1, TSPAN8, MMP28, NNMT, SERPINA5, LUM, and FDXR). C-reactive protein (CRP) was assessed with a specific assay, while nicotinamide N-methyltransferase (NNMT) was evaluated in the patient serum by enzyme-linked immunosorbent assay.

Results

A multiple regression analysis showed that the level of CRP in the serum is correlated with the POAD LF stages (r² = 0.22, P = 0.046) and that serum NNMT is higher in IV LF POAD patients (P = 0.005). The mRNA gene expression of LUM is correlated with the LF stage (r² = 0.45, P = 0.009), and the mRNA level of ITLN1 is correlated with the ankle-brachial index (r² = 0.42, P = 0.008).

Conclusions

Our analysis shows that NNMT, ITLN1, LUM, CFD, and TSPAN8 in combination with other known markers, such as CRP, could be evaluated as a panel of biomarkers of POAD.