Antimicrobial activity of zinc-doped hydroxyapatite coatings formed on titanium Ti6A14V surface for orthopedic implant

Prosthetic joint infection (PJI) is one of the most serious complications of prosthetic joint implantation leading to a longer hospitalization. S. aureus is the predominant cause of PJI followed by Pseudomonas aeruginosa and Stafilococci spp. coagulase negative. Several studies focused on the development of effective antibacterial surfaces that prevent bacterial adhesion, colonisation and proliferation into the surrounding tissues and it has been widely demonstrated that zinc ions (Zn2+) exhibit antimicrobial activity against various bacterial and fungal strains. In addition to its antimicrobial activities, zinc is important in healthy bone growth and development. The aim of this study was to evaluate the in vitro activity of Zn2+ generated from the partial dissolution of Zn particles on surface of titanium discs, against S. aureus ATCC 29213. Hydroxyapatite (HA), and HA/Zn2+ doped discs were used. Each disc was incubated with bacterial suspension following standard ASTM (American Society for Testing and Materials) method. After, colony-forming unit (CFU) were counted. The results showed 1,7 log10 (97,8 %) CFU decrease vs untreated samples (p< 0.05), after 6 hours of incubation. To confirm quantitative data, morphological analysis was performed by Scanning Electron Microscope (SEM). On HA disc, bacteria, recognized by the typical spherical shape, colonized micro and nano porosities surface assuming an homogeneous distribution, while on the surface doped with Zn2+, being smoother and less porous, the bacteria adhered to the surface in small colonies of about 2-10 bacteria. This new formulation of zinc coating could represent a promising approach for prevention and treatment of peri-implant diseases

Hypertension in adult Fabry's disease: is cardiotrophin-1 a diagnostic biomarker?

Background: Cardiotrophin-1 (CT-1), a cytokine produced by cardiomyocytes and non-cardiomyocytes in conditions of stress, can be used as a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients. Hypertension is one of the main adverse events in the third and last phase of Fabry's disease (FD). We measured CT-1 in order to examine its correlation with the vascular and cardiac alterations at different ages and assess its potential for use as a biomarker of hypertension in FD. Findings: The level of CT-1 was clearly higher in hypertensive adults than in adult FD patients. FD patients show a small, non-significant decrease in plasma CT-1 with age, while in hypertensive patients CT-1 in plasma rises strongly and highly significantly with age. Conclusions: CT-1 can be considered a good biomarker of the progression of hypertension with age, but particular care is needed when following hypertension in FD patients, since CT-1 does not correlate the same way with this disease

Unique features of the mode of action of ET-743

This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743

Effects of Vitamin E-Stabilized Ultra High Molecular Weight Polyethylene on Oxidative Stress Response and Osteoimmunological Response in Human Osteoblast

High Crosslink process was introduced in the development of joint prosthetic devices, in order to decrease the wear rate of ultrahigh molecular weight polyethylene (UHMWPE), but it also triggers the formation of free radicals and oxidative stress, which affects the physiological bone remodeling, leading to osteolysis. Vitamin E stabilization of UHMWPE was proposed to provide oxidation resistance without affecting mechanical properties and fatigue strength. The aim of this study is to evaluate the antioxidant effect of vitamin E added to UHMWPE on oxidative stress induced osteolysis, focusing in particular on the oxidative stress response in correlation with the production of osteoimmunological markers, Sclerostin and DKK-1, and the RANKL/OPG ratio compared to conventional UHMWPE wear debris. Human osteoblastic cell line SaOS2 were incubated for 96 h with wear particles derived from crosslinked and not crosslinked Vitamin E-stabilized, UHMWPE without Vitamin E, and growth medium as control. Cellular response to oxidative stress, compared to not treat cells, was evaluated in terms of proteins O-GlcNAcylation, cellular levels of OGA, and OGT proteins by immunoblotting. O-GlcNAcylation and its positive regulator OGT levels are increased in the presence of Vitamin E blended UHMWPE, in particular with not crosslinked Vit E stabilized UHMWPE. Conversely, the negative regulator OGA increased in the presence of UHMWPE not blended with Vitamin E. Vitamin E-stabilized UHMWPE induced a decrease of RANKL/OPG ratio compared to UHMWPE without Vitamin E, and the same effect was observed for Sclerostin, while DKK-1 was not significantly affected. In conclusion, Vitamin E stabilization of UHMWPE increased osteoblast response to oxidative stress, inducing a cellular mechanism aimed at cell survival. Vitamin E antioxidant effect influences the secretion of osteoimmunological factors, shifting the bone turnover balance toward bone protection stimuli. This suggests that Vitamin E-Stabilization of UHMWPE could contribute to reduction of oxidation-induced osteolysis and the consequent loosening of the prosthetic devices, therefore improving the longevity of total joint replacements

Healing of bronchopleural fistula using a modified Dumon stent: a case report

BACKGROUND: Brochopleural fistula following lung resection is a therapeuric challenge for thoracic surgeons. CASE PRESENTATION: We describe a case of late bronchopleural fistula after right extrapleural pneumonectomy for malignant mesothelioma. Bronchoscopic attempts to repair it were unsuccessful. CONCLUSION: The use of a modified Y Dumon stent associated with glue apposition on the bronchial stump allowed us to close the fistula without the need of any surgical repair

Toll-like receptor 2 in serum: a potential diagnostic marker of prosthetic joint infection?

Prosthetic joint infection (PJI) is a severe complication of arthroplasty and is still lacking diagnostic gold standards. PJI patients display high Toll-like receptor 2 (TLR2) serum levels, correlating with canonical inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-\u3b1], and IL-1). Therefore, TLR2 serum levels could be considered a new potential diagnostic tool in the early detection of PJI. Copyright \ua9 2014, American Society for Microbiology

Evaluation of circulating sRAGE in osteoporosisaccording to BMI, adipokines and fracture risk: a pilot observational study

Background: Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. Results: Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. Conclusions: The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis