Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. If left untreated, PKU results in increased phenylalanine concentrations in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. PKU management differs widely across Europe and therefore these guidelines have been developed aiming to optimize and standardize PKU care. Professionals from 10 different European countries developed the guidelines according to the AGREE (Appraisal of Guidelines for Research and Evaluation) method. Literature search, critical appraisal and evidence grading were conducted according to the SIGN (Scottish Intercollegiate Guidelines Network) method. The Delphi-method was used when there was no or little evidence available. External consultants reviewed the guidelines. Using these methods 70 statements were formulated based on the highest quality evidence available. The level of evidence of most recommendations is C or D. Although study designs and patient numbers are sub-optimal, many statements are convincing, important and relevant. In addition, knowledge gaps are identified which require further research in order to direct better care for the future.

The complete European guidelines on phenylketonuria: diagnosis and treatment

Evaluation of cytotoxicity and physicochemical properties of calcium silicate-based endodontic sealer MTA Fillapex.

Three bioceramic sealers (EndoSequence BC sealer, EndoSeal MTA, and MTA Fillapex) and three epoxy resin-based sealers (AH-Plus, AD Seal, and Radic-Sealer) were tested to evaluate the physicochemical properties: flow, final setting time, radiopacity, dimensional stability, and pH change. The one-way ANOVA and Tukey’s post hoc test were used to analyze the data ( ). The MTA Fillapex sealer had a highest flow and the BC Sealer presented a flow significantly lower than the others ( ). The BC Sealer and MTA Fillapex samples were not set in humid incubator condition even after one month. EndoSeal MTA had the longest setting time among the measurable materials and Radic-Sealer and AD Seal showed shorter setting time than the AH-Plus ( ). AH-Plus and EndoSeal MTA showed statistically higher values and MTA Fillapex showed statistically lower radiopacity ( ). BC Sealer showed the highest alkaline pH in all evaluation periods. Set samples of 3 epoxy resin-based sealers and EndoSeal MTA presented a significant increase of pH over experimental time for 4 weeks. In conclusion, the bioceramic sealer and epoxy resin-based sealers showed clinical acceptable physicochemical properties, but BC Sealer and MTA Fillapex were not set completely.

/pdf/physicochemical-properties-of-epoxy-resin-based-and-53hwj5sbl3.pdf

Physicochemical Properties of Epoxy Resin-Based and Bioceramic-Based Root Canal Sealers.

https://lbmd.coe.pku.edu.cn/PDF/2015JOE.pdf

In Vitro Cytotoxicity of Calcium Silicate–containing Endodontic Sealers

During the past two decades, a number of major advances have been made in the field of bioactive ceramics used for endodontic treatment. This article reviews the physico-chemical and biological properties of bioceramic materials and the application of bioceramic technology to endodontics. Bioceramic materials, with their biocompatible nature and excellent physico-chemical properties, are widely used in endodontic applications. They can function as cements, root repair materials, root canal sealers and filling materials, which have the advantages of enhanced biocompatibility, potential increased root strength following obturation, antibacterial properties and sealing ability. New bioceramic materials have demonstrated the ability to overcome some of the significant limitations of earlier generations of endodontic materials. Most bioceramic materials have been shown to be biocompatible and have good physico-chemical characteristics, therefore having a potential use in clinical endodontics. Although in vitro studies on the use of bioceramic materials in endodontics have given encouraging results, randomized and double-blind clinical studies of sufficient length with these materials are needed to confirm long-term success following their use.

Bioceramic materials in endodontics

Scelza MZ, Linhares AB, da Silva LE, Granjeiro JM, Alves GG. A multiparametric assay to compare the cytotoxicity of endodontic sealers with primary human osteoblasts. International Endodontic Journal, 45, 12–18, 2012.

Abstract
Aim  To compare the cytotoxicity of four endodontic sealers (Sealapex, Pulp Canal Sealer EWT, Real Seal and MTA Fillapex) either 1 or 7 days after mixing, when assessed through a multiparametric analysis employing human primary cells closely related to periapical tissues.

Methodology  Extracts of each sealer were prepared following 24-h exposure to culture media, at either 24 h or 7 days after mixing. Primary human osteoblasts were exposed to extracts for 24 h, at 37 °C with 5% CO2, and cell viability was evaluated by a multiparametric assay assessing sequentially, on the same cells, mitochondrial activity (XTT), membrane integrity (neutral red test) and total cell density (crystal violet dye exclusion test). Results from each test and experimental time were compared by 2-way analysis of variance (anova).

Results  All endodontic sealers had strong cytotoxicity 24 h after mixing, according to all parameters evaluated. At a longer setting period (7 days), viability for Sealapex was significantly increased (P < 0.05) and Pulp Canal Sealer achieved levels of cytocompatibility similar to the control group. The anova indicated a general correlation between the cytotoxicity of the materials and the time after mixing, with some level of dependence on the cell viability assay employed.

Conclusions  All materials had high cytotoxic levels for human primary cells, mostly on a time-dependent basis, as shown by three different cell viability tests.

A multiparametric assay to compare the cytotoxicity of endodontic sealers with primary human osteoblasts

Individuals with phenylketonuria (PKU, OMIM 261600) have shown bone disease from childhood. Factors such as non-adherence to treatment, nutritional inadequacy, and high phenylalanine levels are associated with bone disease in several studies. This research aimed to describe the impact of dietary factors (consumption of energy, protein, calcium, phosphorus, and phenylalanine), and the control of plasma phenylalanine levels on bone age (BA) and bone mineral density (BMD). Thirteen patients of both genders, from 8 to 16 years old participated in this study. Control data were collected of phenylalanine levels, food frequency and record, hand and fist X-rays, and spinal bone densitometry. In children group (CG), individuals non-adherent to diet (NAD) consumed lower amounts of calcium (472 ± 100 mg/day) and energy (1743 ± 486 Kcal); they had higher rates of phenylalanine (564 ± 94 μmol/L) in blood, intake phenylalanine (701 ± 334 mg/g), and higher protein intake from free foods (14 ± 6.67 g/day); bone age (BA) values higher than the chronological age (CA) and less BMD values (−0.7 ± 1.6 SD) also were verified. In adolescent group (AG, N = 8) of NAD, values were lower for energy intake (1379 ± 258 Kcal), calcium (801 ± 152 mg/day), phosphorus (657 ± 102 mg/day), food protein (25 ± 7.6 g/day), and intake phenylalanine (1067 ± 382 mg/day) than recommended. Higher levels of plasma phenylalanine (851 ± 244 μmol/L), bone age greater than chronological age and lower BMD values (−2.4 ± −2.5 SD) were observed. The results suggest effects on BA and on BMD, in both children and adolescent groups. The bone development is expressed differently in children and adolescents. The non-adherence to the diet verified in both groups and the consequent imbalance in the nutrients intake involved in bone metabolism suggest that these factors influence the failure to thrive in children and reduced bone mineralization in adolescents.

Bone development in children and adolescents with PKU.

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A multiparametric assay to compare the cytotoxicity of endodontic sealers with primary human osteoblasts

Bone development in children and adolescents with PKU.