Association Between Chronic Exposure to Arsenic and Slow Nerve Conduction Velocity Among Adolescents in Taiwan

The association between chronic exposure to arsenic and peripheral neuropathy has been controversial in previous studies, which may be due to the influence of factors, such as age, gender, chronic diseases, occupational injuries, and arsenic exposure. To clarify the question of this association, a cross-sectional study was designed. In total, 130 junior high school students aged 12-14 years were included and exami-ned for the motor and sensory nerve conduction velocity of peripheral nerves in their right-upper and lower limbs. Concentrations of arsenic in well-water and history of drinking well-water were retrieved from a baseline database created in 1991. After adjustment for gender and height, a significant odds ratio of 2.9 (95% confidence interval [CI] 1.1-7.5) was observed for the development of slow nerve conduction velocity of the sural sensory action potential (SAP) among the study subjects with a cumulative arsenic dosage of >100.0 mg. In addition, a borderline statistical significance with odds ratio of 7.8 (95% CI 1.001-69.5) for the development of slow nerve conduction velocity of sural SAP was also observed among the study subjects who drank well-water containing arsenic concentrations of >50.0 \u3bcg/L and with a cumulative arsenic dosage of >100.0 mg. The study found that chronic exposure to arsenic might induce peripheral neuropathy. It also found that the slowing of the nerve conduction velocity of sural SAP might be an early marker of chronic arsenic neuropathy

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

<p>Abstract</p> <p>Background</p> <p>Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.</p> <p>Methods</p> <p>To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.</p> <p>Results</p> <p>The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, <it>p </it>= 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.</p> <p>Conclusions</p> <p>The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.</p

GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure

<p>Abstract</p> <p>Background</p> <p>Arsenic is a strong stimulus of heme oxygenase (HO)-1 expression in experimental studies in response to oxidative stress caused by a stimulus. A functional GT-repeat polymorphism in the HO-1 gene promoter was inversely correlated to the development of coronary artery disease in diabetics and development of restenosis following angioplasty in patients. The role of this potential vascular protective factor in carotid atherosclerosis remains unclear. We previously reported a graded association of arsenic exposure in drinking water with an increased risk of carotid atherosclerosis. In this study, we investigated the relationship between HO-1 genetic polymorphism and the risk of atherosclerosis related to arsenic.</p> <p>Methods</p> <p>Three-hundred and sixty-seven participants with an indication of carotid atherosclerosis and an additional 420 participants without the indication, which served as the controls, from two arsenic exposure areas in Taiwan, a low arsenic-exposed Lanyang cohort and a high arsenic-exposed LMN cohort, were studied. Carotid atherosclerosis was evaluated using a duplex ultrasonographic assessment of the extracranial carotid arteries. Allelic variants of (GT)n repeats in the 5'-flanking region of the HO-1 gene were identified and grouped into a short (S) allele (< 27 repeats) and long (L) allele (≥ 27 repeats). The association of atherosclerosis and the HO-1 genetic variants was assessed by a logistic regression analysis, adjusted for cardiovascular risk factors.</p> <p>Results</p> <p>Analysis results showed that arsenic's effect on carotid atherosclerosis differed between carriers of the class S allele (OR 1.39; 95% CI 0.86-2.25; <it>p </it>= 0.181) and non-carriers (OR 2.65; 95% CI 1.03-6.82; <it>p </it>= 0.044) in the high-exposure LMN cohort. At arsenic exposure levels exceeding 750 μg/L, difference in OR estimates between class S allele carriers and non-carriers was borderline significant (<it>p </it>= 0.051). In contrast, no such results were found in the low-exposure Lanyang cohort.</p> <p>Conclusions</p> <p>This exploratory study suggests that at a relatively high level of arsenic exposure, carriers of the short (GT)n allele (< 27 repeats) in the HO-1 gene promoter had a lower probability of developing carotid atherosclerosis than non-carriers of the allele after long-term arsenic exposure via ground water. The short (GT)n repeat in the HO-1 gene promoter may provide protective effects against carotid atherosclerosis in individuals with a high level of arsenic exposure.</p

[[alternative]]On the effectiveness of Instructing Junior High School Students to Solve Proportion Problems by Polya's Mathematical Problem Solving Heuristics

[[abstract]]The purpose of this study is to explore the effectiveness of one month (16 classes,each 50 minutes)of teaching junior secondary students to solve proportion problemsby means of Polya's problem solving heuristics. This study adopted a nonequivalent-group pretest posttest design on two classes of eighth graders(22 students each)that were taught by the same teacher in a medium-ability school in Taipei city.One of the classes,the experimental groupal,was taught proportion with frequent emphasis on various Polya's problem solving heuristics as were laid out in the book,"How to solve It."In contrast,the control group was taught by the traditionallecturing method. Various types of data were collected,including pri-and posttestof knowledge in proportion,questionnaire of students' attitude towards mathematicsbefore and after instruction,as well as the experimental group's attitude towardsPolya's heuristics. The questionnaire was found to consist of three factors,namely,attitude towards learning nathenatics,attitude towards doing mathematics,and attribution for success in examinations. Various data analyses were performed,including multivariate ANOVA of such independent variables as field independenceand formal thinking on various test/item scores,as well as detailed analyses ofstrategies used by students. It was found that the two groups were basically equivalentin terms of their prior knowledge of proportion,as well as starting abilities in understanding the problem,diagram drawing,field independence and formal thinking.The result from this study indicated that Polya's approach was readily acceptableby eighth graders.With respect to the first phase of Polya's approach,the experimentalgroup performed significantly better than the control group regarding their performancein "understanding the problem"and"drawing to facilitate problem solving.Moreover,students who handled more abstract thinking were found to perform better than thosewith lower abilities.As regards the second and third phase,the result was less obvious.The differences in problem solving ability before and after instruction were insignificant between the two groups.Though most students still view mathematicalproblems as cinstituting only one solution,one particular student in the experimentalgroup twice furnished more than one solution in the posttest. In addition,the extent of satisfaction derived from furnishing a new solution was significantlyhigher for the experimental group than in the control group. In general,students'attitude towards mathmatics learning was,after instruction,better for the experimentalthan the control group.Yet the enhancement of attitude from pretest time was notdifferent between the two groups.Also,it was found that field dependency and formalthinking had significant disordinal interaction effect on students' attitude towardslearning mathematics.In particular,among the field dependent individuals,those who were also formal thinkers held significantly better attitude over the lessformal group.On the other hand,formal thinkers had significantly better attitudetowards doing mathematics than nonformal thinkers,as did those instructed underPolya's approach rather the lecturing approach. As regards the learning of proportion,students in both classes were weak in the concept of concentration as well as its difference fromproportion.Based on the results of this study,it is suggested that teachers shouldhelp students, especially those who are easily mislead while problem solving,to appreciate the importance of understanding the problem.Students should be given chances to enculturate a rich problem solving experience.Problem solving shouldbe integrated into and diffused throughout the school curriculum.Besides,teachersshould enable students to construct meaningful proportion concept,preferably withrespect to other subject areas.Teachers should also encourage students to explaintheir procedures to make sure that they understand the mathematics concepts behind.Future study may consider extending the instruction period as well as including features from the metacognition literature.

EFFECT OF PLASMA HOMOCYSTEINE LEVEL AND URINARY MONOMETHYLARSONIC ACID ON THE RISK OF ARSENIC-ASSOCIATED CAROTID ATHEROSCLEROSIS

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S- adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA(V)) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high- performance liquid chromatography (HPLC). Proportion of MMA( V) (MMA %) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA(V), and dimethylarsinic acid (MMA(V)). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P = 16.5%) and high homocysteine levels ( >= 12.7 mu mol/l) as compared to those with low MMA % (< 9.9%) and low homocysteine levels (12.7 mu mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine. (c) 2006 Elsevier Inc. All rights reserved

Effect of heme oxygenase-1 gene promoter polymorphism on cancer risk by histological subtype: A prospective study in arseniasis-endemic areas in Taiwan

Heme oxygenase (HO)-1 is upregulated by many stressful stimuli, including arsenic. A GT-repeat ((GT)n) polymorphism in the HO-1 gene promoter inversely modulates the levels of HO-1 induction. Previous HO-1 (GT)n polymorphism studies in relation to cancer risk have shown disparate results. We prospectively investigated the associations between HO-1 (GT)n polymorphism and cancer risk related to arsenic from drinking water. Totally, 1,013 participants from community-based cohorts of arseniasis-endemic areas in Taiwan were followed for 13 years. Allelic polymorphisms were classified into long (L, 27 (GT)n) and short (S, &lt;27 (GT)n). Newly developed cases were identified through linkage with National Cancer Registry of Taiwan. Multivariate Cox proportional hazard methods were used to evaluate effects of the HO-1 polymorphism alone or combined with arsenic exposure. Results showed that participants with the S/S genotype had an increased risk of Bowen's disease (HR=10.49; 95% CI: 2.77-39.7), invasive skin cancer (HR=2.99; 95% CI: 1.13-7.87), and lung squamous cell carcinoma (HR=3.39; 95% CI: 1.15-9.95) versus those with L/S or L/L genotype. The S/S genotype combined with high arsenic exposure (&gt;300 g/L) had a greater risk of skin cancer compared to the genotype alone. Consistent with previous findings, participants with the S-allele had a reduced risk of lung adenocarcinoma (HR=0.21; 95% CI: 0.03-0.68) versus those with L/L genotype. There were no significant differences in risk of urothelial carcinoma among the three genotypes. Associations of HO-1 (GT)n polymorphism with cancer risk differs by histological subtype and the polymorphism should be considered a modifier in the risk assessment of arsenic exposure. ;What's new? Heme oxygenase (HO)-1 defends cells against oxidative stress, but its protective effects are modulated by polymorphisms that shorten or lengthen the number of GT dinucleotide repeats in the gene promoter. Here, among cohorts in areas of Taiwan affected by endemic arsenic poisoning, individuals who were homozygous for short (GT)n polymorphisms (S/S, &lt;27 dinucleotide repeats) were found to be at increased risk of skin cancer and lung squamous cell carcinoma. Arsenic exposure further increased skin cancer risk among S/S individuals. All S-allele carriers, however, had a reduced risk of lung adenocarcinoma, a malignancy unrelated to arsenic exposure

A Prospective Study of Gynecological Cancer Risk in Relation to Adiposity Factors: Cumulative Incidence and Association with Plasma Adipokine Levels

Background: Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. ;Methods: Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels. ;Findings: There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28-5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI &gt;= 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. ;Conclusion: We provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin

This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02–12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78–42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04–26.8) and 32.3 (95% CI: 3.94–265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort