RESUMO
Enzymatic browning caused by polyphenol oxidases, tyrosinase and laccase, continues to be one of the main problems in winemaking. Therefore, wineries are very interested in studying the mechanisms of browning and procedures for decreasing the use sulphur dioxide. This research proposes a model to study tyrosinase activity from grape must using different substrates: one monophenol (p-hydroxybenzoic acid), two diphenols (caftaric acid and (-)-epicatechin) and one triphenol (gallic acid). The kinetic constants of tyrosinase, Vmax and KM, indicate that caftaric acid is the best substrate for tyrosinase, followed in decreasing order by (-)-epicatechin, gallic acid and p-hydroxybenzoic acid. This last acid does not appear to be susceptible to browning by the action of grape must tyrosinase. The influence of pH, temperature and ethanol on grape must tyrosinase were also determined and the results indicate that tyrosinase Vmax increases when pH and temperature are higher and that the presence of ethanol reduces it.
RESUMO
BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30-50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24-48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: -0.87, SD 9.4, p = 1 × 10-5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10-8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.
RESUMO
PURPOSE: To determine whether Repetitive Extragenic Palindromic PCR (rep-PCR) genotyping can improve the diagnosis of coagulase-negative staphylococcal (CoNS) orthopaedic infections in comparison to phenotyping. METHODS: Prospective study comparing the results of phenotypic/genotypic (rep-PCR) testing in patients with suspected CoNS infection. Each strain was analysed using both methods. Strains identified as identical in ≥2 samples were considered as pathogenic. RESULTS: 255 CoNS strains from 52 surgical episodes were included. Infection was diagnosed by phenotyping in 38(73%) cases and by genotyping in 40(77%). The Kappa index was 0.59. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for phenotyping (vs. rep-PCR) were: 88%, 75%, 92%, and 64%. 5/14(36%) of cases not considered as true infections by phenotyping were diagnosed as infections with genotyping. In a subgroup of 203 strains from 41 surgical procedures with orthopaedic implants, the kappa index was 0.68. Sensitivity, Specificity, PPV, and NPV for phenotyping were: 93%, 73%, 90% and 80%. Again, 2/10 episodes in which CoNS were considered non-infective by phenotyping were diagnosed as infected by genotyping. CONCLUSIONS: Rep-PCR genotyping can identify identical CoNS strains that differ in their phenotype and should be used as a complementary technique. One-third of infected cases may be misdiagnosed without genotypic analysis.