Bulk-fill resin-based composite restorative materials: a review.

Resin-based composite (RBC) materials are increasingly being used for the restoration of posterior teeth. The increasing demand for aesthetic, tooth-coloured restorations coupled with the patient's concerns regarding the use of mercury containing restorations, has driven a surge in the use of RBC materials. With the Minamata Convention in 2013 calling for the phase-out of dental amalgam and dental schools increasingly teaching techniques for RBC restorations in posterior teeth, it is likely that the dental profession's reliance upon RBC for the restoration of posterior teeth will only increase. In order to simplify and speed-up the placement of large posterior RBCs, manufacturers have produced a range of materials which can be placed in single or deeper increments, known as bulk-fill RBCs. Over a relatively short period of time many bulk-fill RBCs have been marketed quoting increment depths between 4-10 mm. The placement of these larger increments of RBC may reduce the time needed when placing posterior restorations and thereby reduce technique sensitivity. This article aims to review the properties and handling characteristics of the bulk-fill RBC materials currently available, while advising the optimal techniques of placement.

Dens invaginatus: diagnosis and management strategies.

Dens invaginatus is a developmental malformation, in which there is an infolding of enamel into dentine. These infolds represent stagnation sites for bacteria and can predispose to dental caries. The carious infection can spread via enamel and dentine to contaminate the pulp and cause soft tissue necrosis. The altered and sometimes complex anatomy of affected teeth can make endodontic management challenging. Early diagnosis is therefore essential as prophylactic treatment of the dens can prevent degeneration and pulpal necrosis. The aim of this article is to review the aetiology, classification, diagnosis and management of teeth affected with dens invaginatus. Emphasis will be placed on describing the clinical features of this anomaly. Treatment options, management strategies and the challenges faced in managing this condition will be discussed.

Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus.

Safety data were pooled and analyzed from one phase 2 and two phase 3 double-blind, placebo-controlled, repeat-dose systemic lupus erythematosus (SLE) trials of belimumab 1, 4 (phase 2 only), and 10 mg/kg. Types and rates of adverse events (AEs) were similar across treatment groups. Rates of patients experiencing any serious AE were 16.6%, 19.5%, 13.5%, and 18.0% with placebo, and belimumab 1, 4, and 10 mg/kg, respectively; rates of serious infusion reactions (including hypersensitivity reactions) occurring on the same days as infusions were 0.4%, 0.9%, 0%, and 0.9%, and rates of serious infections were 5.5%, 7.1%, 6.3%, and 5.3%. Malignancy rates/100 patient-years (excluding non-melanoma skin cancer) were 0.29 with placebo vs. 0.20 with all belimumab doses combined; mortality rates/100 patient-years were 0.43 vs. 0.73. These data support the conclusion that belimumab in combination with standard SLE therapy was generally well tolerated in a predominantly autoantibody-positive population with active SLE.

Local carboplatin delivery and tissue distribution in livers after radiofrequency ablation.

This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.

The measurement of the main PGE metabolite, 13,14-dihydro-15-keto prostaglandin E by radioimmunoassay using methyl oxime stabilization.

The measurement of 13,14-dihydro-15-keto prostaglandin E2 [PGEM] is complicated by the artefactual formation of compounds of the corresponding A series which are reactive towards protein. Existing methods of assay depend on the deliberate dehydration to the 'A' form followed by cyclization in alkaline solution to a bicyclic derivative which is stable and can be measured by radioimmunoassay. We report an alternative approach using methyl oximation of the 9- and 15-keto groups which confer stability on the molecule. This derivatization is simple and does not involve an active intermediate such as those of the PGA series. The antiserum for radioimmunoassay is raised against the methyl oxime form. The label is the methyl oxime of PGEM coupled to a tripeptide Pro-gly-tyr through the nitrogen in the proline ring. This is a linkage distinct from that used to raise the antiserum and thus is not preferentially recognized over the endogenous analyte; this results in a high sensitivity assay. The results correlated well with those from the bicyclic assay when both assays were used to measure the same samples of peripheral blood from women receiving a sustained release PGE pessary for ripening the cervix. The technique provides a rapid and reliable method for determining prostaglandin E metabolites.

Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis.

A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack.

A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis.

The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.

Urate crystal-induced chemotactic factor: isolation and partial characterization.

A factor with chemotactic properties for neutrophils and mononuclear cells was extracted from the lysosomal fraction of both human and rabbit neutrophils that had been allowed to phagocytose monosodium urate crystals. The chemotactic factor was found to be a glycoprotein with a mol wt of 8,400 daltons. The factor is heat labile and has chemotactic activity for human as well as rabbit cells. Preincubation of the cells with the urate induced chemotactic factor or with complement activated plasma prevents the cell from migrating chemotactically when challenged with either factor in the chemotactic chamber. The chemotactic factor induces release of lysosomal enzymes for cytochalasin B treated human neutrophils.

Fluorimetric method for the detection of anti-DNA antibodies in serum.

A method for the detection of native anti-DNA antibodies in serum is described. The method is based on the reactivity of fluorescein isothiocyanate with DNA, forming a complex capable of combining with anti-DNA antibodies. The fluorescein content of the precipitated fluorescein-DNA anti-DNA complex is then measured in a fluorometer. The assay is accurate, highly reproducible, and inexpensive to perform. Comparative studies performed with the Farr assay show the fluorimetric method to be more sensitive in detecting anti-DNA antibodies in the serum of SLE patients.

Studies on crystal-induced chemotactic factor. II. Role of phagocytosis.

The interaction of polymorphonuclear leukocytes (PMN's) and urate crystal leads to the formation of a chemotactic factor. The purpose of this study was to determine the need for ingestion of crystals by the cells in the generation of the chemotactic factor. Our studies showed that when PMN's were incubated with cytochalasin B, an inhibitor of phagocytosis, and urate crystals, no chemotactic activity appeared in the lysosomal extract of the cells. Likewise, no chemotactic activity was present in the media of PMN's incubated with crystals although lysosomal enzyme activity was increased. These findings indicate that phagocytosis is required for chemotactic activity to appear. Our studies also show that cytochalasin B increases the release of lysosomal enzyme B-glucuronidase but not of cytoplasmic enzyme lactic dehydrogenase from PMN's when the cell encounters urate crystals.