Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder

Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method: Eighty-nine stimulant-naive children with ADHD 7 to 11 years old participated in a randomized, double-blind, crossover trial of long-acting MPH. Parents and teachers assessed each child\u27s response on placebo and three MPH dosage levels using the Vanderbilt ADHD rating scales. Children were genotyped for polymorphisms in the 3′ untranslated region of dopamine transporter (DAT), exon 3 on dopamine receptor D4 (DRD4), codon 158 on catechol-O-methyltransferase, and the adrenergic α2A-receptor promoter. Linear mixed models evaluated gene, dose (milligrams per kilogram per day), and gene-by-dose effects on inattentive and hyperactive-impulsive domain outcomes. Results: The most statistically significant gene-by-dose interactions were observed on hyperactive-impulsive symptoms for DRD4 and DAT polymorphisms, with participants lacking the DAT 10-repeat allele showing greater improvements in symptoms with increasing dose compared with 10-repeat carriers (p = .008) and those lacking the DRD4 4-repeat allele showing less improvement across MPH doses compared with 4-repeat carriers (p = 0.02). Conclusions: This study suggests that DAT and DRD4 polymorphisms may be associated with individual variability in MPH dose-response, although further research in larger samples is required to confirm these findings and their clinical utility. Clinical trial registration information--Response Variability in Children with Attention-Deficit/Hyperactivity Disorder (ADHD); http://www.clinicaltrials.gov; NCT01238822. © 2011 American Academy of Child and Adolescent Psychiatry

Anti-fungal and anti-bacterial activities of ethanol extracts of selected traditional Chinese medicinal herbs

Objective To evaluate in vitro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential. Methods A total of 58 traditional Chinese medicinal plants were carefully selected based on the literature review and their traditional use. The antimicrobial activities of ethanol extracts of these medicinal plants were tested against fungi (Aspergillus fumigatus), yeast (Candida albicans), gram-negative (Acinetobacter baumannii and Pseudomonas aeruginosa) and gram-positive bacteria (Staphylococcus aureus). The activities were tested at three different concentrations of 1.00, 0.10 and 0.01 mg/mL. The data was analysed using Gene data Screener program. Results The measured antimicrobial activities indicated that out of the 58 plant extracts, 15 extracts showed anti-fungal activity and 23 extracts exhibited anti-bacterial activity. Eight plant extracts have exhibited both anti-bacterial and anti-fungal activities. For instance, Eucommia ulmoides, Polygonum cuspidatum, Poria cocos and Uncaria rhyncophylla showed activity against both bacterial and fungal strains, indicating their broad spectrum of activity. Conclusions The results revealed that the ethanol extracts of 30 plants out of the selected 58 possess significant antimicrobial activities. It is interesting to note that the findings from the current study are consistent with the traditional use. A clear correlation has also been found between the antimicrobial activity and the flavonoid content of the plant extracts which is in agreement with the literature. Hence, the results presented here can be used to guide the selection of potential plant species for the isolation and structure elucidation of novel antimicrobial compounds in order to establish the structure-activity relationship. This in turn is expected to lead the way to the discovery of novel antimicrobial agents for therapeutic use

Effects of Meals High in Carbohydrate, Protein, and Fat on Ghrelin and Peptide YY Secretion in Prepubertal Children

Context: Ghrelin and peptide YY (PYY) are two hormones produced by the gastrointestinal tract that have effects on appetite. However, little is known about their secretion in response to meals high in individual macronutrients in prepubertal children

Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: Due to significant individual variability in Attention Deficit/Hyperactivity Disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examines the role of 4 catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. METHOD: 89 stimulant-naïve children with ADHD aged 7–11 participated in a randomized, double-blind, crossover trial of long-acting MPH. Parents and teachers assessed each child’s response on placebo and three MPH dosage levels using the Vanderbilt ADHD rating scales. Children were genotyped for polymorphisms in the dopamine transporter’s (DAT) 3’ untranslated region, dopamine receptor D(4)‘s (DRD4) exon 3, catechol-O-methyltransferase’s (COMT) codon 158, and adrenergic α(2A)-receptor’s (ADRA2A) promoter. Linear mixed models evaluated gene, dose (mg/kg/day), and gene*dose effects on inattentive and hyperactive-impulsive domain outcomes. RESULTS: The most statistically significant gene*dose interactions were observed on hyperactive-impulsive symptoms for DRD4 and DAT polymorphisms, with participants lacking the DAT 10-repeat allele experiencing greater improvements in symptoms with increasing dose compared to 10-repeat carriers (p=0.008), and those lacking the DRD4 4-repeat allele showing less improvement across MPH doses compared to 4-repeat carriers (p=0.02). CONCLUSIONS: This study suggests that DAT and DRD4 polymorphisms may be associated with individual variability in methylphenidate dose-response, although further research in larger samples is required to confirm these findings and their clinical utility