Classification of children as slow or rapid acetylators based on concentrations of isoniazid in saliva folowing oral administration of body-weight and surface-area-related dosages of the drug

The acetylator phenotype of 180 children aged 3-11 years was determined on the basis of isoniazid concentrations in saliva collected at 5 hours after oral administration of body-weight and surfacearea- related &sages of the drug in a syrup form. isoniazid 25 mglkg was administered on one occasion and 75 mg/m2 surface-area on another, with an interval of 3 days between the occasions. A cross-over design was employed and the sequence was determined by random allocation. The distribution of the concentrations was bimodal with both procedures, indicating the presence of two groups namely, the slow and rapid acetylators. The criterion for a rapid acetylator was a concentration of 0.3 μg/ml or less by body-weight-related dosage and 0.4 μg/ml or less by that based on surface-area. Based on these criteria, 62 % of the children were classified as slow acetylators and 38% as rapid acetylators by body-weight, and 59 and 41 %, respectively by surface-area, and the findings were similar in children in the different age-groups. The agreement between the two procedures was 98%

Persistent Organic Chemicals in the Pacific Basin Countries: An Overview

The Pacific Basin is a unique geographical region representing tropical, temperate and polar zones. This region is home to 2/3 of world’s population and consists of rapidly growing economies (countries) and highly developed countries. The Pacific Basin countries have had a history of use of persistent organic chemicals (POCs) at varying proportions during the last five decades. Due to diverse climatic and socio-economic conditions, the environment and biota in different countries in this basin have varying degrees of environmental contamination and effects on wildlife and humans. In this chapter, the historical background of POCs including, discovery, production, use, regulations/restrictions imposed, current status and possible future trends are reviewed especially focusing on the countries in the Pacific Rim

A novel homozygous TPM1 mutation in familial pediatric hypertrophic cardiomyopathy and in silico screening of potential targeting drugs.

Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. While sarcomeric gene mutations explain many HCM cases, the genetic basis of about half of HCM cases remains elusive. Here we aimed to identify the gene causing HCM in a non-consanguineous Saudi Arabian family with affected family members and a history of sudden death. The impact of the identified mutation on protein structure and potential drug targets were evaluated in silico. Triplets (two HCM subjects and one patent ductus arteriosus (PDA) case) and unaffected parents were screened by targeted next-generation sequencing (NGS) for 181 candidate cardiomyopathy genes. In silico structural and functional analyses, including protein modeling, structure prediction, drug screening, drug binding, and dynamic simulations were performed to explore the potential pathogenicity of the variant and to identify candidate drugs. A homozygous missense mutation in exon 1 of TMP1 (assembly GRCh37-chr15: 63340781; G>A) was identified in the triplets [two HCM and one patent ductus arteriosus (PDA)] that substituted glycine for arginine at codon 3 (p.Gly3Arg). The parents were heterozygous for the variant. The mutation was predicted to cause a significant and deleterious change in the TPM1 protein structure that slightly affected drug binding, stability, and conformation. In addition, we identified several putative TPM1-targeting drugs through structure-based in silico screening. TPM1 mutations are a common cause of HCM and other congenital heart defects. To date, TPM1 has not been associated with isolated PDA; to our knowledge, this is the first report of the homozygous missense variation p.Gly3Arg in TPM1 associated with familial autosomal recessive pediatric HCM and PDA. The identified candidate TPM1 inhibitors warrant further prospective investigation.This research was supported by the Strategic Technologies Programs of the National Plan for Science, Technology and Innovation (MAARIFAH), Kingdom of Saudi Arabia. Project No: 12-MED3174-05, through the Science and Technology Unit (STU), Taibah University, Al Madinah Al Munawwarah, Kingdom of Saudi Arabia

Sorption-Desorption Behavior of Atrazine on Soils Subjected to Different Organic Long-Term Amendments

Sorption of atrazine on soils subjected to three different organic amendments was measured using a batch equilibrium technique. A higher K(F) value (2.20 kg(-1)(mg L(-1))(-)N) was obtained for soil fertilized with compost, which had a higher organic matter (OM) content. A correlation between the K(Foc) values and the percentage of aromatic carbon in OM was observed. The highest K(Foc) value was obtained for the soil with the highest aromatic content. Higher aromatic content results in higher hydrophobicity of OM, and hydrophobic interactions play a key role in binding of atrazine, On the other hand, the soil amended with farmyard manure had a higher content of carboxylic units, which could be responsible for hydrogen bonding between atrazine and OR Dominance of hydrogen bonds compared to hydrophobic interactions can be responsible for the lower desorption capacity observed with the farmyard manure soil, The stronger hydrogen bonding can reduce the leaching of atrazine into drinking water resources and runoff to rivers and other surface waters

Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics

Influence of Stefan blowing on nanofluid flow submerged in microorganisms with leading edge accretion or ablation

The unsteady forced convective boundary layer flow of viscous incompressible fluid containing both nanoparticles and gyrotactic microorganisms, from a flat surface with leading edge accretion (or ablation), is investigated theoretically. Utilizing appropriate similarity transformations for the velocity, temperature, nanoparticle volume fraction and motile microorganism density, the governing conservation equations are rendered into a system of coupled, nonlinear, similarity ordinary differential equations. These equations, subjected to imposed boundary conditions, are solved numerically using the Runge-Kutta-Fehlberg fourth-fifth order numerical method in the MAPLE symbolic software. Good agreement between our computations and previous solutions is achieved. The effect of selected parameters on flow velocity, temperature, nano-particle volume fraction (concentration) and motile microorganism density function is investigated. Furthermore, tabular solutions are included for skin friction, wall heat transfer rate, nano-particle mass transfer rate and microorganism transfer rate. Applications of the study arise in advanced micro-flow devices to assess nanoparticle toxicity