Hernia repair is one of the most common operations in general surgery, and its associated complications typically relate to infections, among others. The loading of antibiotics to surgical meshes to deliver them locally in the abdominal hernia repair site can be one way to manage infections associated with surgical implants. However, the amount of drug loaded is restricted by the low wettability of polypropylene (PP). In this work, plasma has been used to tailor the surface properties of PP meshes to obtain high loading of ampicillin while conserving the desired biological properties of the unmodified samples and conferring them with antibacterial activity. It was demonstrated that the new surface chemistry and improved wettability led to 3-fold higher antibiotic loading. Subsequently, a PEG-like dry coating was deposited from tetraglyme with low-pressure plasma which allowed maintaining the high drug loading and kept cell properties such as chemotaxis, adhesion and morphology to the same levels as the untreated ones which have shown long-standing clinical success.
We have described recently the Ets family transcription factor, ERM/ETV5, specifically up-regulated in endometrioid endometrial carcinoma (EEC) and associated with myometrial infiltration. Ets family members have been correlated to tumor progression by up-regulating the expression of matrixdegrading proteases. In the present study, we investigated the possibility that in EEC, ERM/ETV5 may act by inducing the expression of genes involved in extracellular matrix remodeling. Unraveling the molecular events associated with the initiation of tumor invasion would represent an obvious improvement for EEC patients. The overexpression of ERM/ ETV5 induced scattering in the endometrial cancer cell line Hec-1A, correlating to increased matrix metalloproteinase-2 (MMP-2) gelatinase activity. Both chromatin immunoprecipitation and reversion experiments with RNA interference and specific MMP-2 inhibitor showed a functional link between ERM/ETV5 overexpression and MMP-2 activation. The increased MMP-2 activity associated with overexpressed ERM/ETV5 in a mouse model conferred invasive capacity to endometrial tumors. Orthotopically implanted overexpressing ERM/ETV5 tumors presented a more aggressive and infiltrative pattern of myometrial invasion. Finally, the specific localization of ERM/ETV5 and MMP-2 at the invasive front of myometrial infiltrating human endometrial carcinomas further reinforced the hypothesis of a role for ERM/ETV5 in the early steps of endometrial dissemination. Taken together, these results lead us to propose that in EEC, ERM/ETV5 acts through MMP-2 gelatinolytic activity to confer invasive capabilities, associated with an initial switch to myometrial infiltration. They also postulate ERM/ETV5 as a valuable marker for patient stratification and a transcription pathway that should be evaluated for therapies specifically targeting the initial steps of EEC dissemination. [Cancer Res 2007;67(14):6753-9]
We conclude that combined therapy of tacrolimus and steroids induce sustained remission of proteinuria in a significant number of patients with idiopathic focal glomerulosclerosis whose disease was not controlled by the standard therapy of steroids and cyclosporin A.
In vivo studies have shown that cancer-associated skeletal muscle wasting (cachexia) is mediated by two cytokines, tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6). It has been unclear from these studies whether TNF exerts direct effects on skeletal muscle and/or whether these effects are mediated via IL-6. Previous studies from our laboratory have shown that TNF induces IL-6 mRNA expression in cultured skeletal muscle cells. To further investigate the relationship between TNF and IL-6, the effects of TNF and IL-6 on protein and DNA dynamics in murine C2C12 skeletal myotube cultures were determined. At 1000 U/ml, TNF induced 30% increases in protein and DNA content. The effects of TNF on protein accumulation were inhibited by aphidicolin, an inhibitor of DNA synthesis. IL-6 mimicked the effects of TNF on C2C12 cultures, inducing a 32% increase in protein accumulation and a 71% increase in the rate of protein synthesis. IL-6 also decreased expression of mRNA for several proteolytic system components, including ubiquitin 2.4 kb (51%) and 1.2 kb (63%), cathepsin B (39%) and m-calpain (47%), indicating that IL-6 acts on both protein synthesis and degradation. Incubation of murine C2C12 myotube cultures with TNF (1000 U/ml) in the presence of a polyclonal mouse anti-IL-6 antibody resulted in an abolishment of the effects of TNF on protein synthesis, but did not inhibit TNF-induced stimulation of DNA synthesis. These findings indicate that the effects of TNF on muscle protein synthesis are mediated by IL-6, but that TNF exerts IL-6-independent effects on proliferation of murine skeletal myoblasts.
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