Bone dimensional variations at implants placed in fresh extraction sockets: a multilevel multivariate analysis

Aim: To use multilevel, multivariate models to analyze factors that may affect bone alterations during healing after an implant immediately placed into an extraction socket. Material and methods: Data included in the current analysis were obtained from a clinical trial in which a series of measurements were performed to characterize the extraction site immediately after implant installation and at re‐entry 4 months later. A regression multilevel, multivariate model was built to analyze factors affecting the following variables: (i) the distance between the implant surface and the outer bony crest (S‐OC), (ii) the horizontal residual gap (S‐IC), (iii) the vertical residual gap (R‐D) and (iv) the vertical position of the bone crest opposite the implant (R‐C). Results: It was demonstrated that (i) the S‐OC change was significantly affected by the thickness of the bone crest; (ii) the size of the residual gap was dependent of the size of the initial gap and the thickness of the bone crest; and (iii) the reduction of the buccal vertical gap was dependent on the age of the subject. Moreover, the position of the implant opposite the alveolar crest of the buccal ridge and its bucco‐lingual implant position influenced the amount of buccal crest resorption. Conclusions: Clinicians must consider the thickness of the buccal bony wall in the extraction site and the vertical as well as the horizontal positioning of the implant in the socket, because these factors will influence hard tissue changes during healing. To cite this article:
Tomasi C, Sanz M, Cecchinato D, Pjetursson B, Ferrus J, Lang NP, Lindhe J. Bone dimensional variations at implants placed in fresh extraction sockets: a multilevel multivariate analysis.
Clin. Oral Impl. Res. 21 , 2010; 30–36.     

High-dose folate and dietary purines promote scavenging of peroxynitrite-derived radicals – Clinical potential in inflammatory disorders

Reduced folates have been shown to reconstitute the proper activity of “uncoupled” endothelial nitric oxide synthase in inflamed endothlelium. There is recent evidence that this phenomenon may reflect an ability of reduced folates to scavenge peroxynitrite – or, more likely, nitrogen dioxide and carbonate radicals derived from carbonate-induced decomposition of peroxynitrite. This suggests that, at least in those tissues capable of achieving high intracellular levels of reduced folates following high-dose folate administration, high-dose folate may have important anti-inflammatory potential. It would be of interest to examine the impact of high-dose folate in rodent models of disorders in which peroxynitrite plays a key pathogenic role – including diabetes, septic or hemorrhagic shock, ischemia-reperfusion, congestive heart failure, and inflammatory mutagenesis. In particular, this strategy may be useful in many pathologies in which oxidant-mediated PARP activation leads to cell death or dysfunction. Recent evidence that high-dose folate administration preserves myocyte viability following cardiac ischemia-reperfusion likely reflects folate’s impact on the cytotoxicity of peroxynitrite. For use in medical emergencies, parenteral leucovorin (racemic 5-formyltetrahydrofolate) is already clinically available. Since uric acid can also function physiologically as a scavenger of peroxynitrite-derived radicals, supplemental inosine or dietary nucleic acids – which raise tissue levels of urate more effectively than does oral uric acid – may usefully complement the protective impact of high-dose folate on nitroxidative stress. Epidemiological associations of high urate levels with low risk for Parkinson’s disease may reflect urate’s radical scavenging activity, and suggest the possible utility of dietary purines in prevention or treatment of CNS inflammatory disorders.     

Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets

The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer.     

Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

Background  

Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors.