Novel combined UGT1A1 mutations in Crigler Najjar Syndrome type I.

BACKGROUND: Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. The A (TA) 7TAA allele has been identified as the most frequent allele in the Caucasian populations while A (TA) 8TAA allele remains the rarest allele worldwide in North Africa, including the Arab populations. METHODS: The spectrum of UGT1A1 genetic mutations in seventeen Tunisian children affected by persistent unconjugated hyperbilirubinemias is represented in addition to their relatives, notably parents, sisters, and brothers. Tunisian children, from 16 unrelated families as well as a 17th family without CN1 affected child, were originated from the West Center of Tunisia. The promoter region and coding exons of the UGT1A1 were PCR amplified, subsequently subjected to Sanger sequencing. RESULTS: The frequencies of genotypes in CN1 patients were as follows (TA) (7/7) (12/17: 70.6%) and (TA) (8/8) (5/17: 29.4%). All patients harbored the c.1070A>G mutation of exon 3 (UGT1A1*16) in the homozygous state. Among relatives of our patients (n = 16), who were all heterozygotes for UGT1A1*16, 13/16 (81.25%) had a heterozygous state for UGT1A1∗1/UGT1A1∗28 or (TA) (6/7) and, 18.75% (3/16) were heterozygous for UGT1A1∗28/UGT1A1∗37 or (TA) (7/8) of the promoter polymorphisms. CONCLUSION: UGT1A1*16 accompanied with UGT1A1*28 or UGT1A1*37 had a specific geographic and ethnic distribution for CN pathogenesis in this Tunisian cohort.

Effect of HA Content on Microstructure and Properties of Ti-27Nb-17Ta-8Zr/HA Composite.

In this paper, Ti-27Nb-17Ta-8Zr/HA series composite materials were prepared by spark plasma sintering (SPS) technology. The medical titanium alloy (Ti-27Nb-17Ta-8Zr) with good mechanical properties, wear resistance, and corrosion resistance was combined with the hydroxyapatite (HA) bioactive ceramic with high biological activity and bone-binding ability. Moreover, the density, microstructure evolution, metal/ceramic reaction, mechanical behavior, in vitro bioactivity, and influencing mechanisms of composite materials with different HA contents were studied. The research results indicate that all biological composite materials are composed of ß-Ti solution, α-Ti, and ceramic phases (Ti2O, CaTiO3, CaO, TixPy). With the increase of HA content, the compressive strength and yield strength of the composite material show a trend of first increasing, then decreasing, and then slowly increasing. After soaking in SBF artificial simulated body fluid for 5 days, the deposition of elements such as Ca and P on the surface significantly increased, while elements such as Ti, Nb, Ta, and Zr were evenly distributed in the matrix, demonstrating good in vitro mineralization ability and facilitating the attachment and growth of osteoblasts.

Microstructure and Mechanical Properties of Ti-25Nb-4Ta-8Sn Alloy Prepared by Spark Plasma Sintering.

As the commercially most-used Ti-6Al-4V alloy has a different modulus of elasticity compared to the modulus of elasticity of bone and contains allergenic elements, ß-Ti alloy could be a suitable substitution in orthopedics. The spark plasma sintering (SPS) method is feasible for the preparation of materials, with very low porosity and fine-grained structure, leading to higher mechanical properties. In this study, we prepared quaternary Ti-25Nb-4Ta-8Sn alloy using the spark plasma sintering method. The material was also heat-treated in order to homogenize the structure and compare the microstructure and properties in as-sintered and annealed states. The SPS sample had a modulus of elasticity of about 63 ± 1 GPa, which, after annealing, increased to the value of 73 ± 1 GPa. The tensile yield strength (TYS) of the SPS sample was 730 ± 52 MPa, ultimate tensile strength (UTS) 764 ± 10 MPa, and ductility 22 ± 9%. Annealed samples reached higher values of TYS and UTS (831 ± 60 MPa and 954 ± 48 MPa), but the ductility decreased to the value of 3 ± 1%. The obtained results are discussed considering the observed microstructure of the alloy.