Pharmacogenetic comparison of CYP2D6 predictive and measured phenotypes in a South African cohort.

This corrects the article DOI: 10.1038/tpj.2015.76.

Pharmacogenetic comparison of CYP2D6 predictive and measured phenotypes in a South African cohort.

The relationship between genetic variation in CYP2D6 and variable drug response represents a potentially powerful pharmacogenetic tool. However, little is known regarding this relationship in the genetically diverse South African population. The aim was therefore to evaluate the relationship between predicted and measured CYP2D6 phenotype. An XL-PCR+Sequencing approach was used to determine CYP2D6 genotype in 100 healthy volunteers and phenotype was predicted using activity scores. With dextromethorphan as the probe drug, metabolic ratios served as a surrogate measure of in vivo CYP2D6 activity. Three-hour plasma metabolic ratios of dextrorphan/dextromethorphan were measured simultaneously using semi-automated online solid phase extraction coupled with tandem mass spectrometry. Partial adaptation of the activity score system demonstrated a strong association between genotype and phenotype, as illustrated by a kappa value of 0.792, inter-rater discrepancy of 0.051 and sensitivity of 72.7%. Predicted phenotype frequencies using the modified activity score were 1.3% for poor metabolisers (PM), 7.6% for intermediate metabolisers (IM) and 87.3% for extensive metabolisers (EM). Measured phenotype frequencies were 1.3% for PM, 13.9% for IM and 84.8% for EM. Comprehensive CYP2D6 genotyping reliably predicts CYP2D6 activity in this South African cohort and can be utilised as a valuable pharmacogenetic tool.

[Changes in the genome of African swine fever virus (Asfarviridae: Asfivirus: African swine fever virus) associated with adaptation to reproduction in continuous cell culture].

INTRODUCTION: African swine fever virus (ASFV) is a large, double-stranded DNA virus in the Asfarviridae family. It is the causative agent of African swine fever (ASF). Only the genome of BA71V strain, adapted to Vero cell culture, was fully analyzed.The aim of this study was analyzing the complete genome sequence of two strains of adapted to the growth in CV-1 cell culture (CC) ASFV obtained after 30 and 50 passages, in comparison to the parental virus. MATERIAL AND METHODS: ASFV isolate Odintsovo 02/14 (parental), ASFV adapted variants ASFV/ARRIAH/CV-1/30 and ASFV/ARRIAH/CV-1/50 were all used to extract genomic DNA (gDNA). Sequencing library was constructed using the «Nextera XT DNA library preparation kit¼ («Illumina¼, USA). RESULTS: Genomes of ASFV/ARRIAH/CV-1/30 and ASFV/ARRIAH/CV-1/50 consisted of 186 529 bp and 186 525 bp, respectively. Total 78 single nucleotide polymorphisms (SNPs) were identified between the parental Odintsovo 02/14 and the two high passaged strains, as well as a 2947 bp large-size deletion in the 3' variable region of adapted viruses was detected. DISCUSSION: ASFV as a DNA-containing virus may not have a very high level of mutation, but this is the second study showing that adaptation to growth in continuous CC leads to large deletions in the genome of the virus. CONCLUSION: Mutations in the protein-coding regions of the genome can be synonymous and non-synonymous, i.e. leading to amino acid substitution. Additional research is needed to understand the influence of the mutations described in the adaptation process on the reproduction of the virus and its virulence.

A variant of Tietze's syndrome occurring after reconstructive breast surgery.

Costosternal chondrodynia (Tietze's syndrome variant) should be considered in those rare patients who present with severe breast pain several months after reconstructive breast surgery. The authors treated 25 cases, 3 of which are discussed in detail, where the origin of the pain was traced to the costosternal cartilages. The differential diagnosis and management of this hitherto undescribed problem after breast surgery are discussed.

Relative bioavailability of four controlled-release nifedipine products.

Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailability of two 10 mg controlled-release nifedipine tablets (Adalat Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat XL) have better controlled-release properties than the Adalat Retard product, and are suitable for once-a-day administration.