Magnetic resonance spectroscopy and molecular studies in ornithine transcarbamylase deficiency novel mutation c.802A>G in exon 8 (p.Met268Val)

Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited defect in ureagenesis, resulting in hyperammonaemia type II. The OTC gene, localised on chromosome X, has been mapped to band Xp21.1, proximate to the Duchenne muscular dystrophy (DMD) gene. More than 350 different mutations, including missense, nonsense, splice-site changes, small deletions or insertions and gross deletions, have been described so far. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Most mutations in the OTC gene are ‘private’ and are distributed throughout the gene with a paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. They have familial origin or occur de novo. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remainder probably occur within the introns or in regulatory domains. The authors present a 4-year-old boy with the unreported missense mutation c.802A>G. The nucleotide transition leads to amino acid substitution Met to Val at codon 268 of the OTC protein.     

The effect of acrylamide incorporation on the thermal and physical properties of denture resins

PURPOSE

Polymethyl methacrylate (PMMA) is the most commonly used denture base material despite typically low in strength. The purpose of this study was to improve the physical properties of the PMMA based denture base resins (QC-20, Dentsply Ltd., Addlestone, UK; Stellon, AD International Ltd, Dentsply, Switzerland; Acron MC; GC Lab Technologies Inc., Alsip, Japan) by copolymerization mechanism.

MATERIALS AND METHODS

Control group specimens were prepared according to the manufacturer recommendations. In the copolymer groups; resins were prepared with 5%, 10%, 15% and 20% acrylamide (AAm) (Merck, Hohenbrunn, Germany) content according to the moleculer weight ratio, respectively. Chemical structure was characterized by a Bruker Vertex-70 Fourier transform infrared spectroscopy (FTIR) (Bruker Optics Inc., Ettlingen, Germany). Hardness was determined using an universal hardness tester (Struers Duramin, Struers A/S, Ballerup, Denmark) equipped with a Vickers diamond penetrator. The glass transition temperature (T_g) of control and copolymers were evaluated by Perkin Elmer Diamond DSC (Perkin Elmer, Massachusetts,USA). Statistical analyses were carried out using the statistical package SPSS for Windows, version 15.0 (SPSS, Chicago, IL, USA). The results were tested regarding the normality of distribution with the Shapiro Wilk test. Data were analyzed using ANOVA with post-hoc Tukey test (P<.01).

RESULTS

The copolymer synthesis was confirmed by FTIR spectroscopy. Glass transition temperature of the copolymer groups were higher than the control groups of the resins. The 10%, 15% and 20% copolymer groups of Stellon presented significantly higher than the control group in terms of hardness. 15% and 20% copolymer groups of Acron MC showed significantly higher hardness values when compared to the control group of the resin. Acrylamide addition did not affect the hardness of the QC-20 resin significantly.

CONCLUSION

Within the limitation of this study, it can be concluded that copolymerization of PMMA with AAm increased the hardness value and glass transition temperature of PMMA denture base resins.     

Peel strength of denture liner to PMMA and polyamide: laser versus air-abrasion

PURPOSE

This study investigated the effect of laser parameters and air-abrasion on the peel strength of silicon-based soft denture liner to different denture resins.

MATERIALS AND METHODS

Specimens (N=180) were prepared out of three different denture base resins (Rodex, cross-linked denture base acrylic resin; Paladent, heat-cured acrylic resin; Deflex, Polyamide resin) (75 mm × 25 mm × 3 mm). A silicon-based soft denture liner (Molloplast B) was applied to the denture resins after the following conditioning methods: a) Air-abrasion (50 µm), b) Er,Cr:YSGG laser (Waterlase MD Turbo, Biolase Technology) at 2 W-20 Hz, c) Er,Cr:YSGG laser at 2 W-30 Hz, d) Er,Cr:YSGG laser at 3 W-20 Hz, e) Er,Cr:YSGG laser at 3 W-30 Hz. Non-conditioned group acted as the control group. Peel test was performed in a universal testing machine. Failure modes were evaluated visually. Data were analyzed using two-way ANOVA and Tukey''s test (α=.05).

RESULTS

Denture liner tested showed increased peel strength after laser treatment with different parameters (3.9±0.4 - 5.58±0.6 MPa) compared to the control (3.64±0.5 - 4.58±0.5 MPa) and air-abraded groups (3.1±0.6 - 4.46±0.3 MPa), but the results were not statistically significant except for Paladent, with the pretreatment of Er,Cr:YSGG laser at 3 W-20 Hz. Polyamide resin after air-abrasion showed significantly lower peel strength than those of other groups (3.1±0.6 MPa).

CONCLUSION

Heat-cured acrylic resin, PMMA, may benefit from Er,Cr:YSGG laser treatment at 3 W-20 Hz irradiation. Air-abrasion of polyamide resins should be avoided not to impair their peel bond strengths to silicon-based soft denture liners.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Glutamate neurons in the substantia nigra compacta and retrorubral field

Dopaminergic neurons of the substantia nigra compacta (SNC), ventral tegmental area (VTA) and retrorubral field (RRF) play a role in reward, motivation, learning, memory, and movement. These neurons are intermingled with GABAergic neurons. Recent evidence shows that the VTA contains glutamatergic neurons expressing vesicular glutamate transporter type 2 (VGluT2); some of them co‐express tyrosine hydroxylase (TH). Here, we used a combination of radioactive in situ hybridisation and immunohistochemistry to explore whether any of the vesicular glutamate transporters [vesicular glutamate transporter type 1 (VGluT1), VGluT2, or vesicular glutamate transporter type 3 (VGluT3)] were encoded by neurons in the SNC or RRF. We found expression of VGluT2 mRNA, but not of VGluT1 or VGluT3, in the SNC and RRF. These VGluT2 neurons rarely showed TH immunoreactivity. Within the SNC, the VGluT2 neurons were infrequently found at the rostral level, but were often seen at the medial and caudal levels intercalated in the mediolateral portion of the dorsal tier, at a ratio of one VGluT2 neuron per 4.4 TH neurons. At this level, VGluT2 neurons were also found in the adjacent substantia nigra reticulata and substantia nigra pars lateralis. Within the RRF, the VGluT2 neurons showed an increasing rostrocaudal gradient of distribution. The RRF proportion of VGluT2 neurons in relation to TH neurons was constant throughout the rostrocaudal levels, showing an average ratio of one VGluT2 neuron per 1.7 TH neurons. In summary, we provide evidence indicating that the SNC and RRF, which are traditionally considered to be dopaminergic areas, have neurons with the ability to participate in glutamate signaling.     

Validation of micro-CT against the section method regarding the assessment of marginal leakage of sealants

Background: The aim of this study was to validate the micro‐CT and related software against the section method using the stereomicroscope for marginal leakage assessment along the sealant‐enamel interface. Methods: Pits and fissures of the occlusal surface of 10 teeth were sealed with a resin‐fissure sealant material without acid etching, thermocycled for 5000 cycles, immersed in 50% silver nitrate for three hours and scanned using micro‐CT. Teeth were embedded in epoxy resin and cut in three sections. The middle section was subjected to micro‐CT and stereomicroscopy. Images were taken from the left and right sides of the sealant‐enamel interface at both the left and the right site of the section. Two experienced evaluators assessed marginal leakage. Results: Both assessment instruments observed no leakage in 37 out of the 40 images evaluated. Leakage at the sealant‐enamel interface was observed in three stereomicroscopy images only. A fracture line in the sealant was seen on eight stereomicroscopy images and observed in only two micro‐CT images. Conclusions: The quality of the micro‐CT and related software used in the present study does not qualify it to replace the section method as the gold standard for marginal leakage assessment at the sealant‐enamel interface of permanent teeth.     

Effect of cariogenic biofilm challenge on the surface hardness of direct restorative materials in situ

Objectives

The presence of cariogenic biofilm could result in surface degradation of composite and ionomeric restorative materials. Thus, this study evaluated in situ the alterations in the surface microhardness of these materials under biofilm accumulation and cariogenic challenge.

Methods

In a split-mouth, double-blind, cross-over study, 10 volunteers wore palatal intra-oral devices containing bovine enamel slabs restored with composite resin (CR – Z250) or resin-modified glass ionomer (RMGI – Vitremer). Two phases of 14 days were carried out, one for each restorative material. In one side of the device, biofilm was allowed to accumulate under a plastic mesh, whereas in the opposing side, regular brushing was carried out 3 times/day with a dentifrice containing 1100 μg F/g as NaF. A 20% sucrose solution was applied extra-orally 10×/day on each restored dental slab. Knoop microhardness was used to calculate the percentage of surface hardness loss (%SHL).

Results

All materials showed a decrease in surface hardness after the in situ period. The restorative materials presented the following average for %SHL: RMGI without biofilm accumulation = 8.9 and with biofilm accumulation = 25.6, CR without biofilm accumulation = 14.7 and with biofilm accumulation = 17.0.

Conclusion

Biofilm accumulation and the presence of cariogenic challenge promoted faster degradation of ionomeric materials, but this was not observed for composite resin.

Clinical significance

The oral environment affects the surface hardness of aesthetic restorative materials. Biofilm accumulation and cariogenic challenge promote surface degradation for ionomeric materials, but not for composite resin.