Design of a randomized controlled double-blind crossover clinical trial to assess the effects of saliva substitutes on bovine enamel and dentin in situ

<p>Abstract</p> <p>Background</p> <p>Hyposalivation is caused by various syndromes, diabetes, drugs, inflammation, infection, or radiotherapy of the salivary glands. Patients with hyposalivation often show an increased caries incidence. Moreover, hyposalivation is frequently accompanied by oral discomfort and impaired oral functions, and saliva substitutes are widely used to alleviate oral symptoms. However, preference of saliva substitutes due to taste, handling, and relief of oral symptoms has been discussed controversially. Some of the marketed products have shown demineralizing effects on dental hard tissues <it>in vitro</it>. This demineralizing potential is attributed to the undersaturation with respect to calcium phosphates. Therefore, it is important to modify the mineralizing potential of saliva substitutes to prevent carious lesions. Thus, the aim of the present study was to evaluate the effects of a possible remineralizing saliva substitute (SN; modified Saliva natura) compared to a demineralizing one (G; Glandosane) on mineral parameters of sound bovine dentin and enamel as well as on artificially demineralized enamel specimens <it>in situ</it>. Moreover, oral well-being after use of each saliva substitute was recorded.</p> <p>Methods/Design</p> <p>Using a randomized, double-blind, crossover, phase II/III <it>in situ </it>trial, volunteers with hyposalivation utilize removable dentures containing bovine specimens during the experimental period. The volunteers are divided into two groups, and are required to apply both saliva substitutes for seven weeks each. After both test periods, differences in mineral loss and lesion depth between values before and after exposure are evaluated based on microradiographs. The oral well-being of the volunteers before and after therapy is determined using questionnaires. With respect to the microradiographic analysis, equal mineral losses and lesion depths of enamel and dentin specimens during treatment with SN and G, and no differences in patients' experienced oral comfort after SN compared to G usage are expected (H₀).</p> <p>Discussion</p> <p>Up to now, 14 patients have been included in the study, and no reasons for early termination of the trial have been identified. The design seems suitable for determining the effects of saliva substitutes on dental hard tissues <it>in situ</it>, and should provide detailed information on the oral well-being after use of different saliva substitutes in patients with hyposalivation.</p> <p>Trial registration</p> <p><b>ClinicalTrials.gov ID. </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01165970">NCT01165970</a></p

RECK - a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer

The RECK (reversion-inducing cysteine rich protein with Kazal motifs) protein was initially discovered by its ability to induce reversion in ras-activated fibroblasts. The key action of RECK is to inhibit matrix metalloproteinases (MMPs) involved in breakdown of the extracellular matrix (ECM), and angiogenesis-namely MMP-2, MMP-9 and MTP-1. To this effect, it plays important physiological roles in embryogenesis and vasculogenesis. Additionally, it has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumours through the ECM. RECK has been studied in the context of a number of human tumours including colorectal, breast, pancreas, gastric, hepatocellular, prostate, and non-small cell lung carcinoma. In many of these tumours, RECK is down-regulated most likely as a result of inhibition at the Sp1 promoter site. MMP-2 and MMP-9 generally show an inverse association with RECK expression, but there are exceptions to this rule. Likewise, a reduction in tumour microvascular density (MVD) and VEGF have also been correlated with increased RECK levels, although more studies are required to define this effect. The predominant finding across all human tumour studies is a significantly improved prognosis (due to decreased invasion and metastasis) in tumours with preserved RECK expression. Although further research is required, RECK is a promising prognostic marker and potential therapeutic agent in multiple cancers