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The aim of this study was to investigate the association of drug-metabolizing enzyme and transporter (DMET) polymorphisms with the risperidone-induced prolactin response using an overlapping gene model between serum prolactin level and hyperprolactinemia in autism spectrum disorder (ASD) patients. Eighty-four ASD patients who were receiving risperidone for at least 1 month were recruited and then assigned to either the normal prolactin group or the hyperprolactinemia group based on their serum prolactin level. The genotype profile of 1936 (1931 single nucleotide polymorphisms (SNPs) and 5 copy number variation (CNVs) drug metabolism markers was obtained using the Affymetrix DMET Plus GeneChip microarray platform. Genotypes of SNPs used to test the accuracy of DMET genotype profiling were determined using TaqMan SNP Genotyping Assay kits. Eighty-four patients were selected for the allelic association study after microarray analyses (51 in the normal prolactin group, and 33 in the hyperprolactinemia group). An overlapping allelic association analysis of both analyses discovered five DMET SNPs with a suggestive association (P< 0.05) with risperidone-induced prolactin response. Three UGT1A1SNPs (UGT1A1*80c.-364C > T, UGT1A1*93 c.-3156G > A, and UGT1A1c.-2950A > G, showed a suggestive association with the risperidone-induced prolactin response and found to be in complete linkage disequilibrium (D′ value of 1). In this DMET microarray platform, we found three UGT1A1variants with suggestive evidences of association with the risperidone-induced prolactin response both measured by hyperprolactinemia and by prolactin level. However, due to the lack of validation studies confirmation and further exploration are needed in future pharmacogenomic studies.

CYP2D6 is involved in the biotransformation of a large number of drugs, including risperidone. This study was designed to detect CYP2D6polymorphisms with a Luminex assay, including assessment the relationship of CYP2D6polymorphisms and risperidone plasma concentration in autism spectrum disorder children (ASD) treated with risperidone. All 84 ASD patients included in this study had been receiving risperidone at least for 1 month. The CYP2D6genotypes were determined by Luminex assay. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Among the 84 patients, there were 46 (55.42%) classified as EM, 33 (39.76%) as IM, and 4(4.82%) as UM. The plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients were significant differences among the CYP2D6predicted phenotype group (P = 0.001 and P < 0.0001 respectively). Moreover, the plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients with CYP2D6 activity score 0.5 were significantly higher than those with the CYP2D6 activity score 2.0 (P = 0.004 and P = 0.002 respectively). These findings suggested that the determination of the accurate CYP2D6genotype-predicted phenotype is essential in the clinical setting and individualization of drug therapy. The use of the Luminex assay for detection of CYP2D6polymorphisms could help us more accurately identify an individual's CYP2D6 phenotype.

The role of cassava (Manihot esculentaCrantz) is rapidly changing from a traditional fresh human food commodity to an efficient crop for agro‐industrial processing in many parts of Asia. Varietal improvement for higher yield and root dry matter content is bringing additional cash income to a great number of small farmers. We documented the yield component data of breeding populations through five evaluation stages with and without selection. We define a best selection scheme based on the genetic, interaction, and error parameters obtained. Important conclusions are (i) broad‐sense heritability and phenotypic correlations obtained at a given selection stage may lead to erroneous selection schemes, (ii) regression across evaluation stages gives the most useful information, (iii) in early evaluation stages, eliminating inferior phenotypes is more beneficial than selecting superior phenotypes, (iv) selection for root dry matter content can be conducted without serious effects on other yield components, (v) harvest index has consistently high heritability at each evaluation stage, while biomass and yield have low heritability, (vi) genotype × evaluation stage interaction for yield is greatest between single‐row and plot trials, while that of harvest index is much smaller [selection at single‐row trials (SRT), usually the second stage of evaluation, is most crucial to the final success of selection for higher yield], and (vii) indirect selection for yield through harvest index is more effective than direct selection by yield itself especially in the early evaluation stages. Realized selection confirmed the conclusions. Actual cultivar dissemination testifies the usefulness of this methodology.

In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the liver, especially of cholangiocarcinoma in the north-eastern provinces of Thailand is associated with the use of tobacco in men infested with the liver fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine in hamsters is significantly increased by infestation with the liver fluke OV. The endogenous formation of nitrosamines is significantly increased by OV infestation. This report presents analytical data on the concentration of volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of nine leading brands of commercially produced Thai cigarettes which represent 85% of the market share in Thailand. Observed ranges (ng/cigarette) were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2-18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared with the smoke of light and blended cigarettes from North America and Western Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. There was a correlation between volatile and tobacco-specific nitrosamines, and tar and nicotine deliveries in the mainstream smoke. The analytical data are in line with the rate for lung cancer and support our working hypothesis that nitrosamines, and especially the tobacco-specific nitrosamines, are associated with the increased risk for primary liver cancer among those Thai people who smoke cigarettes and also carry OV infestation.

Background. Lung cancer is now a major public health problem in Thailand. This descriptive study looked at the issue of whether tumor histology varied with smoking status among lung cancer patients in Bangkok, Thailand. Methods. A retrospective descriptive study was made of the 1,600 Thai patients with histologically proven lung cancer admitted to University of Siriraj Hospital between 1967 and 1991. Cigarette smoking histories were obtained, and histologies were classified and related to tobacco consumption. Results. Overall, 78% were smokers, 72% being heavy smokers. The male to female ratio was 13:1 for smokers and 0.4:1 for nonsmokers. There were 29% squamous cell, 29% adenocarcinoma, 24% large cell, and 13% small cell carcinomas. Squamous cell carcinoma was significantly more frequent among cases with a history of smoking Thai cigarettes, which are known (from other studies) to be high in tar and nicotine, than among nonsmoking cases. Among the 350 nonsmokers, 252 of whom were female, adenocarcinoma was the most common (58%). Conclusions. The results suggest that Thai smokers can reduce their risk for lung cancer by quitting smoking, or by substituting lower tar brands. Antismoking programs should therefore be a public health priority. Given the prevalence of adenocarcinoma among nonsmokers, further work should be done to identify environmental causes.

In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the liver, especially of cholangiocarcinoma in the north-eastern provinces of Thailand is associated with the use of tobacco in men infested with the liver fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine in hamsters is significantly increased by infestation with the liver fluke OV. The endogenous formation of nitrosamines is significantly increased by OV infestation. This report presents analytical data on the concentration of volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of nine leading brands of commercially produced Thai cigarettes which represent approximately 85% of the market share in Thailand. Observed ranges (ng/cigarette) were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2-18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared with the smoke of light and blended cigarettes from North America and Western Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. There was a correlation between volatile and tobacco-specific nitrosamines, and tar and nicotine deliveries in the mainstream smoke. The analytical data are in line with the rate for lung cancer and support our working hypothesis that nitrosamines, and especially the tobacco-specific nitrosamines, are associated with the increased risk for primary liver cancer among those Thai people who smoke cigarettes and also carry OV infestation.