Reference value for C-reactive protein and its distribution pattern in thai adults.

BACKGROUND: To set a reference value for high-sensitivity C-reactive protein (hs-CRP) in a healthy Thai population and study the effect of time, gender and age on that value. METHODS AND RESULTS: Three hundred and sixty-four subjects, aged between 18 and 74 years, comprising 185 men and 279 women, were studied. Another 10 healthy subjects, aged between 18 and 54 years, were recruited for the study of circadian variation in hs-CRP over the days of the week and the months of a year. The reference value for the Thai adults in the present study was 1.8 mg/L, range 0.2-7.9 mg/L. There was no significant difference in the hs-CRP concentration because of region, time, gender or age (p>0.05), nor was the value affected by time. CONCLUSION: The determination of hs-CRP can be performed at any time and the hs-CRP value determined by this study can be used as the reference for Thai adults.     

Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni infected mice and resistance to challenge infection after treatment

The therapeutic effect of a subcurative dosage of praziquantel (PZQ) on Schistosoma mansoni infected mice and resistance to challenged worm infection after treatment were assessed and compared with conventional treatment using a curative dosage of PZQ. S. mansoni infected mice were treated with PZQ at a curative dosage (600 mg kg(-1)) or a subcurative dosage (300 mg kg(-1)) at 9 weeks after infection. Untreated mice and non-infected mice were added as controls. The therapeutic effect of the drug was evaluated in terms of the mortality of mice after treatment, and the parasitological and pathological findings in mice sacrificed at 1 week, 1 month, or 3 months after treatment. Another sample of mice was not killed but challenged with S. mansoni cercariae at 1 week, 1 month, or 3 months after treatment. Resistance to re-infection was evaluated by the extent of challenged worm reduction. In conclusion, there was no significant difference in mortality, or parasitological and pathological findings between mice treated with PZQ at the two dosages. However, resistance to challenged worm infection was more sustained in the group treated with subcurative dose PZQ, especially at 3 months after treatment.     

Evidence for exposure-induced DNA repair abnormality is indicative of health and genetic risk

A recent focus has been targeted toward the development of functional biomarkers that can be used to predict disease more reliably. One such biomarker is the challenge assay for DNA repair deficiency. Briefly, the assay involves challenging lymphocytes in culture to a DNA damaging agent in vitro and determining the repair outcome in chromosome aberrations and/or DNA strand breaks. The aim is to show that individuals who have chronic exposure to toxic substances will develop exposure-induced DNA repair deficiencies. Many studies around the world have shown that the assay detects DNA repair deficiency in environmentally/occupationally exposed populations and with significant exposure dose–response relationship. The prediction of health risk was also validated. In addition, exposure-induced repair deficiency which was apparently passed through the germ cells had caused genetic consequences in a 3-generation population. The assay is simple to conduct and is more sensitive than some traditional biomarker assays. Together with the functional significance of the assay, the challenge assay can be used with confidence in population studies for health risk assessment.     

Use of biomarkers to characterize functions of polymorphic DNA repair genotypes

Inheritance of variant DNA repair genes is believed to influence individual susceptibility to the development of environmental cancer. However, the validity of the belief is dependent upon understanding the functions of the variant genes. Consequently, a variety of studies have been conducted to investigate the functions of variant DNA repair genes, e.g. using biomarkers. These studies on several representative polymorphic DNA repair genes are reviewed in this report. From a general overview, it appears that the biomarker investigations did not provide consistent observations. However, from a more careful evaluation, it is clear that the inconsistencies are probably caused by the use of populations and biomarkers that are not appropriate for investigating the repair activities of the genes. For example, the use of cigarette smokers and patients may not generate precise information for this type of investigations because these conditions can modify the functions of the investigated genes. Thus, the use of healthy non-smokers would be more appropriate. Other problems with these studies includes the small sample size used and the fact that some of the biomarkers used, such as sister chromatid exchanges, are not appropriate because the mechanisms for formation of the biomarkers and their biological significance are unknown. Nevertheless, the following conclusions can be derived from the review of the various biomarker studies that have been published. XRCC1 194Trp, OGG1 326Cys and APE1 148Glu probably have limited alterations in repair activities compared to the wild-type genotypes. XRCC1 399Gln and XRCC3 241Met are deficient in the repair of X-ray-, but not UV-light-induced chromosome aberrations, therefore the variant genes are defective in base excision repair. XPD 312Asn and XPD 751Gln are deficient in the repair of UV-light- but not X-ray-induced chromosome aberrations, therefore they are defective in nucleotide excision repair.     

Measurement of genotoxic air pollutant exposures in street vendors and school children in and near Bangkok

The effects of air pollution on human health are a great concern, particularly in big cities with severe traffic problems such as Bangkok, Thailand. In this study, exposure to genotoxic compounds in ambient air was studied by analysis of particle-associated polycyclic aromatic hydrocarbons (PAHs) and benzene through direct measurement of concentrations in air as well as through the use of different biomarkers of exposure: urinary 1-hydroxypyrene (1-OHP) for PAHs and urinary t,t-muconic acid (t,t-MA) for benzene. The study was conducted in various susceptible groups of the population with different occupations in 5 traffic-congested areas of Bangkok, as well as in primary school children. The level of total PAHs on the main roads at various sites ranged from 7.10 to 83.04 ng/m(3), while benzene levels ranged from 16.35 to 49.25 ppb. In contrast, ambient levels in nearby temples, the control sites, ranged from 1.67 to 3.04 ng/m(3) total PAHs and 10.16 to 16.25 ppb benzene. Street vendors selling clothes were exposed to 16.07 +/- 1.64 ng/m(3) total PAHs and 21.97 +/- 1.50 ppb benzene, levels higher than in monks and nuns residing in nearby temples (5.34 +/- 0.65 ng/m(3) total PAHs and 13.69 +/- 0.77 ppb benzene). Grilled-meat vendors in the same area were exposed to both total PAHs and benzene at even higher levels, possibly due to additional formation of PAHs during the grilling of meat (34.27 +/- 7.02 ng/m(3) total PAHs; 27.49 +/- 2.72 ppb benzene). At the end of the workday, urinary 1-OHP levels in street vendors (0.12 and 0.15 micromol/mol creatinine in clothes and grilled-meat vendors, respectively) were significantly higher than in controls (0.04 micromol/mol creatinine; P < 0.01). Afternoon urinary t,t-MA levels in both groups of street vendors (0.12 mg/g creatinine) were also significantly higher than in controls (0.08 mg/g creatinine; P < 0.05). School children from two schools in Bangkok were exposed to total PAHs and benzene at levels of 6.70 +/- 0.47 ng/m(3) and 4.71 +/- 0.25 ppb, respectively, higher than those to which children living outside the city were exposed (1.25 +/- 0.24 ng/m(3) total PAHs; 2.10 +/- 0.16 ppb benzene). At the end of the school day, levels of urinary 1-OHP and t,t-MA were significantly higher (P < 0.001 and P < 0.01, respectively) in Bangkok school children (0.23 micromol/mol creatinine and 0.27 mg/g creatinine, respectively) than in school children from outside Bangkok (0.10 micromol/mol creatinine and 0.08 mg/g creatinine, respectively).     

Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

Background

Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer.

Objectives

This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure.

Discussion

Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects.

Conclusions

Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.

Citation

Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360     

Dietary Iron Intake and Availability in Hill Tribe and Urban Women,Chiang Rai Province,Northern Thailand

ABSTRACT

Data were collected as part of a cross-sectional study. The objectives were to compare dietary intakes of iron and enhancers and inhibitors of non-heme iron absorption in hill tribe and urban women of Chiang Rai province, northern Thailand, and compare iron- and vitamin C- containing foods sold in markets in both settings. Dietary data were collected using three 24- hour recalls from 128 women aged 19–50 years (hill tribe: n = 65; urban n = 63), and proportions of low-, medium- and high-iron/vitamin C containing foods were surveyed in local markets. Hill tribe women consumed less iron, animal protein, vitamin C and calcium, but market availability of iron/vitamin C foods was similar. Future interventions should focus on food choice modification, to improve intakes of iron and foods that enhance its absorption, especially among hill tribe women.     

Survival of patients with advanced non-small-cell lung cancer at Ubon Ratchathani Cancer Center, Thailand

This survival analysis was conducted at Ubon Ratchathani Cancer Center to determine the prognostic factors for survival of patients with stage IIIA, stage IIIB, and stage IV non-small-cell lung cancer (NSCLC) patients treated at the center between 1997-2001. The study sample included 210 patients with non-small-cell lung cancer. Diagnosis and staging were defined employing the TNM system. The majority of lung cancer patients were smokers (66.7%), lived in Ubon Ratchathani Province (40.0%), male (77.6%), and agriculturalists (74.8%). Seventy-seven percent of patients died within five years, 19.5% were lost to follow-up and 2.9% were still alive in 2003. The estimated median survival time was 6.3 months (95% CI 5.4-7.3); the median survival times for stages IIIA, IIIB, and IV were 16.3, 7.0, and 4.5 months, respectively. The overall 1-, 2- and 3-year survival rates of NSCLC were 28.9, 7.9, and 3.3, respectively. The differences in survival of patients in the various stages of the disease were statistically significant (p < 0.0001), adjusted for age and sex. Treatment with combination methods and at an early stage in the disease were associated with significant prolongation of survival. For stage IIIA, the estimated median survival times by treatment with chemotherapy was 7.0 months, radiotherapy was 16.0 months, surgery and others 16.3 months, and chemotherapy plus radiotherapy was 19.5 months. However, only chemotherapy versus surgery and others was significantly different (p = 0.0307). The median survival times for stage IIIB patients treated with chemotherapy, radiotherapy, surgery and others, chemotherapy and radiotherapy, and supportive treatment were 7.0, 7.0, 9.0, 14.7, and 3.0 months, respectively. The differences between surgery and others versus supportive treatment, chemotherapy and radiotherapy versus supportive treatment were significantly different (p = 0.0392, p = 0.0433, respectively). For stage IV, the median survival times for patients treated with chemotherapy, radiotherapy, chemotherapy and radiotherapy, and supportive treatment were 5.0, 4.3, 6.5, and 1.0 months, respectively. The differences between chemotherapy, radiotherapy, chemotherapy and radiotherapy versus supportive treatment, all were significantly different (p = 0.0020, p < 0.0001, p < 0.0001, respectively). The 2-year survival rates for stages IIIA, IIIB, and IV were 16.0, 4.1, and 2.2%, respectively. The results of the study show that stage IIIA has the longest survival time. They also show that appropriate treatment is a significant factor in improving the survival of lung cancer patients.     

Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line

ABSTRACT: BACKGROUND: Accumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro. METHODS: For the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 muM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 muM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis (COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII. RESULTS: Results showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53 hypermethylation (p < 0.05). However, a slight LINE-1 hypomethylation and transient p53 promoter hypermethylation were observed following long-term in vitro treatment. CONCLUSIONS: This study provides an important finding that in utero arsenic exposure affects DNA methylation, particularly at the p53 promoter region, which may be linked to the mechanism of arsenic carcinogenesis and the observed increased incidence of cancer later in life.     

The effect of thiamine deficiency on the metabolism of acetaminophen (paracetamol)

The effect of thiamine deficiency on the metabolism of acetaminophen (paracetamol) was studied in male and female rats. Deficiency of thiamine enhanced the rate of disappearance of the drug from the plasma which resulted in the apparent decrease in the plasma half-life. The alteration in the rate of acetaminophen metabolism was, in part, due to an increase in the formation of the water soluble metabolites characterized as glucuronide and sulfate conjugates. The effect of thiamine deficiency could be overcome by supplementation with thiamine by intraperitoneal injection. A single large dose of thiamine (650 μg) could reduce the rate to the normal level within 24 hr. However, a series of 5 low doses (260 μg/dose/day) was required to produce the same effect.