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Abstract: Background: Psoriasis is an inflammatory skin condition. Epidemiology studies from different parts of the world have shown that psoriasis is associated with different components of metabolic syndrome. The association between psoriasis and development of cancer has not yet been clearly established. Objective: We hypothesize that chronic inflammation is the driving force that enhances the risk of malignancy in psoriatic patients and suspect that psoriatic patients have higher risks for developing cancers that are most prevalent in the studied population. Methods: Using the nested case–control approach derived from the Taiwanese population-based cohort, the current study was launched to validate this hypothesis. Results 8180 psoriatic patients and 163,600 age-matched controls were included in this study. Psoriatic patients were 1.20 folds (95% CI=1.06–1.36; p =0.004) more likely than controls to develop cancer. Further analyses revealed that incident cancers derived from digestive tract, the most common cancer origin found in Taiwanese population, were most significantly associated psoriasis. Patients with psoriasis and diabetes mellitus, a frequent comorbid condition independently associate with both psoriasis and cancer, conferred the highest risk for developing digestive tract cancers, having risks of 1.98 folds (95% CI: 1.11–3.52) and 1.68 folds (95%CI: 1.23–2.28) for the 41–60years-old and 61–80years-old age group, respectively. Both psoriasis and diabetes were independently associated with development of digestive tract cancers in the 41–60years-old patient group. Conclusion: Prevalent cancers in the population should be carefully monitored in the psoriatic patients after middle age (beyond 40years of age) especially for those with concomitant diabetic conditions. [Copyright &y& Elsevier]

Background: Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous studies have focused mostly on pediatric patients, and investigations emphasizing adult AD have been limited. Objective: We set out to determine the 1-year prevalence and evaluate the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD questionnaires of adult AD in Taiwan. Methods: We conducted a cross-sectional study among nursing staff at a university hospital. The 1-year prevalence of AD was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists'' diagnosis based on Hanifin and Rajka criteria was used as a reference for validation. Results: The overall response rate was 92.9%, equivalent to 1131 complete questionnaires. Ninety adult patients with AD (8%) were identified by dermatologists'' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%) patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively. Using the receiver operating characteristic curve analysis, the UKWP criteria performed significantly better than its ISAAC counterpart. Further analysis indicated that modification of these criteria resulted in significant improvement in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and 55.2% sensitivity and specificity, respectively, whereas modified UKWP demonstrated 82.2% and 94.2% sensitivity and specificity, respectively. Limitation: Most of the study subjects were female with a high educational background. Conclusion: Currently available questionnaire instruments do not perform well in the identification of adult patients with AD. Modification of the original questionnaires may allow for future large-scale epidemiologic studies. [Copyright &y& Elsevier]

Background/purpose: The effect of betel quid chewing on colorectal cancer (CRC) risk has not been reported. In addition, there is no consensus about the causal relationship between smoking or alcohol consumption and CRC risk. This study investigated the impact of betel quid chewing, cigarette smoking or alcohol consumption on CRC risk in Taiwan.Methods: Two hundred and fifty-eight patients with pathologically proven CRC (153 men, 105 women; mean age, 63.1 years) were recruited from two hospitals in southern Taiwan. The controls were 533 age- and gender-matched cancer-free subjects from the same hospitals. All subjects were interviewed using a standardized questionnaire to collect demographic and substance use data.Results: After adjusting for potential confounding factors, smoking (adjusted odds ratio [aOR], 1.65; 95% CI, 1.1-2.3), but not betel quid chewing (aOR, 1.3; 95% CI, 0.7-2.4) or alcohol drinking (aOR, 1.1; 95% CI, 0.7-1.8), was an independent significant risk factor for developing CRC. The significant risk effect of smoking was seen mainly among men, because the frequency of smokers was much higher among Taiwanese men than women.Conclusion: Our results indicated that consumption of cigarettes but not betel quid or alcohol was a risk factor for male CRC. A large study is necessary to investigate the risk factors for female CRC in Taiwan, and to understand the effect of betel quid exposure on male CRC. [ABSTRACT FROM AUTHOR]

A follow-up study was designed to compare the 24-year overall and disease-specific mortality in Yucheng people who were highly exposed to polychlorinated biphenyls/dibenzofurans (PCBs/PCDFs) to that in the background population in Taiwan. In 1979, the Yucheng (oil-disease in Chinese) incident occurred in central Taiwan involving approximately 2000 victims due to ingestion of rice oil contaminated with PCBs/PCDFs. Long-term follow-up of these people has been continued for 24 years. Methods: Standardized mortality ratios were calculated using the Taiwan population as comparison group. Overall and disease-specific mortality was compared between Yucheng and background populations. Results: Mortality from chronic liver disease and cirrhoses was increased in the Yucheng men, but not in women, in the early period after exposure. Cancer mortality was not increased in the Yucheng population up to 24 years after exposure. SLE in females was highly increased in the later period after PCB/PCDF exposure. Mortality from disease in any other organ system was not significantly different between Yucheng and background populations. Conclusions: The study provided a long-term mortality picture after the Taiwanese PCB/PCDF exposure incident. In addition to re-confirming the increase in liver mortality, we found high mortality of SLE among exposed population. This finding highlights the importance of further investigating the immunological effects associated with PCB/PCDF exposure. [Copyright &y& Elsevier]

In Taiwan, a clear gender difference emerges for rates of oropharyngeal carcinoma incidence. The purpose of this study was to identify the gender differences and clinical factors associated with oropharyngeal carcinoma survival rates in Taiwan. We analyzed the 5-year survival rates of 8114 subjects diagnosed with oropharyngeal carcinoma between 1987 and 1994. The Cox proportional-hazards model identified clinical characteristics for gender according to oropharyngeal carcinoma death and all-cause death outcomes. The 5-year survival rates were significantly lower for males than females (p<0.0001). The adjusted hazard ratio of males versus females was 1.54 (95% CI: 1.36–1.74) for oropharyngeal carcinoma death and 1.44 (95% CI: 1.31–1.58) for all-cause death. Gender and other clinical characteristics (i.e. diagnostic age, anatomic site, morphologic type, and treatment modality) play important roles in oropharyngeal carcinoma survival. We suggested that Taiwanese males have high proportion of betel quid chewing and that this is associated with the gender differences. [Copyright &y& Elsevier]

Betel quid (BQ) and areca nut use are at risk of cancer. This review includes the latest evidence of carcinogenesis caused by BQ exposure, suggests possible prevention strategies. We conducted a systematic literature search in the PubMed and Web of Science databases to identify relevant articles published in the past 10 years according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Arecoline N-oxide, a metabolite of areca nut, is likely an initiator in carcinogenesis and is detoxified by N-acetylcysteine. Oral potentially malignant disorder and reactive oxygen species involved in carcinogenesis pathways may be treatable using antioxidants. Screening programs conducted by trained physicians are useful for identifying patients with early stages of oral cancer in high-risk groups. Anti-inflammatory medications may be used as chemopreventive agents in the disease-free stage after surgery. The association between survival and tumor somatic mutations in patients who chew BQ should be addressed in cancer studies. Current evidence on the natural course from BQ exposure to cancer occurrence and development provides information for developing primary, secondary, and tertiary prevention strategies against BQ-associated cancer at clinical or translational levels. [ABSTRACT FROM AUTHOR]

Objective: Many genetic factors have been implicated in the development of oral squamous cell carcinoma (OSCC). Although mutations associated with OSCC have been well documented, the rate of these mutations is known to vary by location. The goal of this study was to determine the frequency of RAS, BRAF, PIK3CA, and TP53 mutations in OSCC within the Taiwanese population. Study Design: A total of 79 OSCC tissue specimens were screened for the presence of RAS, BRAF, PIK3CA, and TP53 mutations. Results: Missense mutations in HRAS were found in 10 of 79 cases (12.66%), and were significantly associated with tumor grade. PIK3CA mutations were observed in 11 of 79 cases (13.92%), including a rare mutation, Q546 P, that had not previously been reported in OSCC. TP53 mutations were observed in 26 of 79 patients (32.91%) and were significantly correlated with poor survival. Conclusions: The results suggest that HRAS, PIK3CA, and TP53 may play a role in OSCC tumorigenesis. [Copyright &y& Elsevier]

Abstract: Epidemiological studies provided evidence that the high dietary intake of flavonoids with fruits and vegetables could be associated with lower cancer prevalence in humans. Didymin, a dietary flavonoid glycoside from citrus fruits, possesses antioxidant properties. This study first investigates the anticancer effect of didymin in human non-small-cell lung cancer A549 and H460 cells. To identity the anticancer mechanism of didymin, we assayed its effect on apoptosis, cell cycle distribution, and levels of p53, p21/WAF1, Fas/APO-1 receptor, and Fas ligand. The results showed that didymin-induced apoptosis of A549 and H460 cells without mediation of p53 and p21/WAF1. We suggest that Fas/Fas ligand apoptotic system is the main pathway of didymin-mediated apoptosis of A549 and H460 cells. Importantly, a novel chemotherapeutic agent for the treatment of non-small-cell lung cancer, and is supported by animal studies which have shown didymin delay the tumor growth in nude mice. Our study reports here for the first time that the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of didymin in A549 and H460 cells. [Copyright &y& Elsevier]

The effect of five lignans isolated from Hernandia nymphaeifolia on estrogenic compounds (17β-estradiol, tamoxifen and clomiphene)-induced Ca2+ mobilization in human neutrophils was investigated. The five lignans were epi-yangambin, epi-magnolin, epi-aschantin, deoxypodophyllotoxin and yatein. In Ca2+–containing medium, the lignans (50–100 μM) inhibited 10 μM 17β-estradiol- and 5 μM tamoxifen-induced increases in intracellular free Ca2+ levels ([Ca2+]i) without changing 25 μM clomiphene-induced [Ca2+]i increase. 17β-estradiol and tamoxifen increased [Ca2+]i by causing Ca2+ influx and Ca2+ release because their responses were partly reduced by removing extracellular Ca2+. In contrast, clomiphene solely induced Ca2+ release. The effect of the lignans on these two Ca2+ movement pathways underlying 17β-estradiol- and tamoxifen-induced [Ca2+]i increases was explored. All the lignans (50–100 μM) inhibited 10 μM 17β-estradiol-and 5 μM tamoxifen-induced Ca2+ release, and 17β-estradiol-induced Ca2+ influx. However, only 100 μM epi-aschantin was able to reduce tamoxifen-induced Ca2+ influx while the other lignans had no effect. Collectively, this study shows that the lignans altered estrogenic compounds-induced Ca2+ signaling in human neutrophils in a multiple manner. [Copyright &y& Elsevier]

Résumé Objectif La consommation d’alcool est fortement associée à l’hyperuricémie, qui peut être responsable de la goutte. Cette étude a évalué le risque de goutte chez des patients présentant des maladies liées à l’alcool et un syndrome de dépendance à l’alcool. Méthodes Nous avons réalisé une étude de cohorte sur la population nationale dans la base de données de recherche nationale d’assurance maladie de Taïwan (NHIRD) afin d’évaluer le risque et l’incidence de la goutte chez les patients présentant des maladies liées à l’alcool et un syndrome de dépendance à l’alcool (selon la définition de la classification internationale des maladies, neuvième révision). Nous avons identifié dans ces dossiers 11 675 cas de maladies liées à l’alcool entre 1998 et 2008. Le groupe témoin comptait 23 350 sujets sans maladie liée à l’alcool appariés par score de propension (1 patient:2 témoins) selon l’âge, la tranche d’âge et le sexe. Résultats Les résultats ont montré que les maladies liées à l’alcool étaient significativement associées au risque de goutte ( hazard ratio ajusté 1,88 ; p < 0,0001). Parmi les patients atteints de maladies liées à l’alcool, 34,1 % présentaient un syndrome de dépendance à l’alcool (hommes 34,8 %, femmes 32,4 %) et la dépendance à l’alcool était indépendamment associée à la survenue de la goutte (risque relatif [RR] 2,01 ; p < 0,0001). Une forte dépendance à l’alcool (correspondant à des patients consommant des quantités importantes de benzodiazépines) a été associée à un risque accru de goutte (RR 1,71–4,21 ; p ≤ 0,0182). Conclusion Les médecins devraient être informés de l’association entre syndrome de dépendance à l’alcool et survenue de goutte, et des évaluations et mesures de la consommation d’alcool visant à prévenir la dépendance devraient être mises en place dans le cadre des soins intégrés aux patients goutteux. [ABSTRACT FROM AUTHOR]

Objective: Alcohol intake is strongly associated with hyperuricemia, which may cause gout. This study evaluated the risk of gout in patients with alcohol-related diseases and alcohol dependence syndrome.Methods: We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nationwide population-based cohort study to assess the risk of gout and gout incidence in patients with alcohol-related diseases and alcohol dependence syndrome (as defined by the International Classification of Diseases, Ninth Revision). In the NHIRD records from 1998 to 2008, we identified 11,675 cases of alcohol-related diseases. The control group comprised 23,350 cases without alcohol-related diseases propensity score-matched (1 case: 2 controls) for age, age group, and sex.Results: The results revealed that alcohol-related diseases were significantly associated with gout risk (adjusted hazard ratio 1.88; P<0.0001). Of the alcohol-related disease cases, 34.1% of the patients had alcohol dependence syndrome (males 34.8%; females 32.4%), and alcohol dependence was independently associated with gout occurrence (relative risk [RR] 2.01; P<0.0001). Severe alcohol-dependent patients (who were also the heavy benzodiazepines users), were associated with an increased risk of gout (RR 1.71 to 4.21, P≤0.0182).Conclusion: Physicians should be aware of the association between alcohol dependence syndrome and gout occurrence, and alcohol use assessment and measures to prevent alcohol dependence should be implemented in the integrative care for patients with gout. [ABSTRACT FROM AUTHOR]

Alpha-kinase 1 (ALPK1) is associated with chronic kidney disease (CKD), type 2 diabetes mellitus and gout. Elevated ALPK1 levels have been observed in the kidneys of patients with diabetes and the white blood cells of patients with gout. As renal injury is a common outcome of CKD, diabetes and gout, the aim of this study was to investigate the effect of ALPK1 in the development of renal injury in a hyperglycemic condition. Hyperglycemia was induced in wild-type and ALPK1 transgenic mice by an intraperitoneal injection of streptozotocin (STZ). Functional and histological examinations were performed after 3 weeks. STZ-treated ALPK1 transgenic mice exclusively showed arteriolar sclerosis and fibrous thickening of the Bowman's capsule in the kidney. This was accompanied by body weight loss, severe hyperglycemia, and low serum insulin levels. Renal renin and serum renin protein levels were higher in STZ-treated ALPK1 transgenic mice, whereas cGKII protein level was decreased by ALPK1 in human embryonic kidney 293 (HEK293) cells. ALPK1 up-regulated TGF-beta1 levels and transcription of fibrosis-related genes, including MMP-9 , FIBRONECTIN , and TIMP1 . MSU crystals increased ALPK1 transcription in cultured kidney cells. Finally, ALPK1 enhanced production of MSU crystals-induced IL-1beta in mice. Stimulation of soluble sodium urate induced IL-1beta and Alpk1 mRNA production in mice kidney. Taken together, these data show that an increase in ALPK1 results in accelerated fibrotic nephropathies, primarily through the enhancement of renin, TGF-beta1, and IL-1beta. Renal or blood ALPK1 levels are involved in the induction of fibrotic renal injury in an experimental model of hyperglycemia. [ABSTRACT FROM AUTHOR]

Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone’s anti-inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone-regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Summary: Substantial epidemiological data suggest a role for environmental factors (for example, the use of alcohol, betel quid (BQ), and cigarettes) in the occurrence of oral squamous cell carcinoma (OSCC), but the evidence for the genes involved has been inconsistent. This study was to investigate the role of CYP26B1, together with the use of alcohol, BQ, and cigarettes, on BQ-related OSCC. The association study (247 OSCC cases and 338 controls) was conducted to examine the possible interplay between CYP26B1 polymorphisms and alcohol, BQ, and cigarettes use. Additional gene expression was evaluated between OSCC tissue and adjacent normal tissue. The genetic polymorphism AA of CYP26B1 appeared to correlate with the risk of OSCC (OR=2.26; 95% CI, 1.35–3.80). Chewing BQ multiplicatively interacted with CYP26B1 AA to increase the OSCC risk (aOR=70.04; 95% CI, 13.62–360.11). The independent risk of OSCC was observed among BQ chewers with CYP26B1 AA, and compared with chewers with the CYP26B1 CC genotype (stratified aOR=2.88; 95% CI, 1.07–7.74). Increased expression of CYP26B1 was observed in tumor tissue compared with adjacent normal tissue. The CYP26B1 gene plays a novel role in the BQ dependent pathogenesis of OSCC. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, areca nut extracts (ANE) administered to male rats by gavage at a dose of 100mg/kg/day for a period of 15, 30, or 45 days resulted in signs of reproductive toxicity. ANE administration resulted in a significant decline (30–57% in epididymal sperm count and 27–61% in sperm motility) as well as substantial abnormalities in sperm morphology. Significant variances in activities of antioxidant enzymes were also observed. Malondialdehyde (MDA) levels, which represent the level of lipid peroxidation, increased by 16–188% and levels of sialic acid decreased by 2–46% compared with that in controls. These results indicate that ANE induced spermatogenic damage, as indicated by a decrease in sperm counts and sperm motility as well as the activity of antioxidant enzymes, an increase in sperm abnormalities, and alterations in sialic acid and MDA levels. Such effects reflect that ANE administration resulted in reactive oxygen species (ROS)-induced oxidative stress in the testis, cauda epididymis, and sperm of male rats. [Copyright &y& Elsevier]

Abstract: In considering documented developmental toxicity and teratogenicity found in earlier research, maternal betel quid chewing may very well be linked to a higher risk of adverse birth outcomes. The aim of this study was to investigate the significance of betel quid chewing, together with the use of cigarettes or alcohol, either independently or combined, on birth-related outcomes. A total of 1264 aboriginal women who had just given birth in 10 hospitals in Southern and Eastern Taiwan were recruited. Information on their maternal and newborn characteristics was obtained from medical charts and by performing personal interviews using a validated questionnaire. Maternal areca nut chewing during pregnancy was found to be significantly associated with both birth weight loss (−89.54g) and birth length reduction (−0.43cm). A significantly lower male newborn rate (aOR=0.62) was observed among aboriginal women with a habit of betel quid chewing during pregnancy. The use of this substance conveyed a 2.40- and 3.67-fold independent risk of low birth weight and full-term low birth weight, respectively. An enhanced risk (aOR=3.26–5.99) of low birth weight was observed among women concomitantly using betel quid, cigarette and alcohol during gestation. Our findings suggest that betel quid chewing during pregnancy has a substantial effect on a number of birth outcomes, including sex ratio at birth, lower birth weight and reduced birth length. [Copyright &y& Elsevier]

Dioxin-responsive element-mediated chemical activated luciferase expression (DRE-CALUX) is one of alternative bioassays for the determination of dioxin levels. We have previously established a DRE-CALUX cell line, Huh7-DRE-Luc, by using stable transfection of Huh-7 cells with a reporter plasmid (4xDRE-TATA-Luc) carrying a DRE-driven firefly luciferase gene. It was also shown that arecoline, a major areca nut alkaloid, inhibited the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cytochrome P450 1A1 (CYP1A1) activation in Huh-7 cells. The TCDD-activated aryl hydrocarbon receptor (AhR) induces the DRE-CALUX activation and CYP1A1 gene expression via binding to DRE in promoter regions of these dioxin-responsive genes. In the present study, the effect of arecoline on the TCDD-induced activation of DRE-CALUX and CYP1A1 enzyme in Huh7-DRE-Luc and Huh-7 cells, respectively, was examined. It was found that arecoline inhibited TCDD-induced CYP1A1 activation and however enhanced TCDD-induced DRE-CALUX activation. This finding indicates the differential effect of arecoline on the endogenous dioxin-responsive CYP1A1 and on a stably transfected DRE-driven reporter in human hepatoma cells. The present study suggests that induction of DRE-CALUX alone does not necessarily parallel with endogenous CYP1A1 gene expression, and that the reporter assay may detect interactions that are not functional in endogenous gene. [Copyright &y& Elsevier]

In the present study, we investigated the effect of arecoline, a major areca nut alkaloid, on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of cytochrome P4501A1 (CYP1A1) in a human hepatoma cell line Huh-7. We treated Huh-7 cells with 10nM TCDD in the presence of different concentrations of arecoline (50–300μM). Our results indicated that arecoline attenuated the TCDD-induced CYP1A1 enzyme activation with an inhibitory effect on cell proliferation. By using real-time RT-PCR, we demonstrated that arecoline inhibited the TCDD-induced activations of CYP1A1 and AhR repressor (AhRR) mRNA expression in a similar pattern. Our results revealed that arecoline inhibited AhR mRNA expression with no direct effect on CYP1A1 enzyme activity. Therefore, in our present study, the observed inhibitory effect of arecoline on CYP1A1 activation was not due to the up-regulation of AhRR or direct inhibitory effect on CYP1A1. Taken together, here we have demonstrated that arecoline attenuates the TCDD-induced CYP1A1 activation mainly via down-regulation of AhR expression in human hepatoma cells, suggesting the possible involvement of arecoline in the AhR-mediated metabolism of environmental toxicants in liver. [Copyright &y& Elsevier]

Abstract: This study used a large-scale cancer database in determining the survival prognostic factors among primary liver cancer (PLC) subjects. A total of 28,939 subjects diagnosed with PLC were analysed. Survival estimates were performed with Kaplan–Meier methods. Cox’s proportional-hazards model estimated the death risk (hazard ratio (HR)) of prognostic factors. The prognostic indicators associated with higher risk of all-cause deaths are male gender (males versus females; HR=1.16, 95% confidence intervals (CI), 1.13–1.20), diagnosis at later period (shown in 1990–1994 versus 1985–1989; HR=1.04, 95% CI, 1.01–1.08), increasing age at diagnosis, subjects with adenocarcinoma/cholangiocarcinoma (CC) and with no therapy against those with chemotherapy. The overall 5-year survival rate for all causes of death was significantly poorer in males (13.7%) than females (17.2%). Subjects diagnosed with hepatoblastoma and treated by surgical resection alone had superior prognosis. Particularly, subjects with adenocarcinoma and CC were more likely to die in other metastatic cancer. [Copyright &y& Elsevier]

Abstract: The soil metal contamination arising from the discharge of the high density of electroplating factories in the geographic center of Taiwan has prompted concern about human exposure to harmful metals. This study aimed to determine the levels of nickel (Ni) in urine of residents living in the high vs. low factory-density areas, and to examine how these levels relate to gender and age. A total of 660 subjects, resident in the area for the last five years, were sampled according to the stratified random sampling approach, at ages 35–44, 45–54, and 55–64years for both genders. Metals in urine samples were analyzed by inductively coupled plasma mass spectrometry (ICPMS). The geometric mean (95% confidence interval (CI)) of urinary Ni was 6.30 (5.99–6.62)μg/l. The 0.95 parametric reference interval (90% CI) of urinary Ni was estimated to be 1.74 (1.62–1.88) to 22.73 (21.14–24.44)μg/l. Subjects in the areas with a high density of electroplating factories had significantly higher urinary Ni levels than those in the low-density areas, but both types of areas had obviously higher urinary Ni levels when compared to the non-occupationally exposed population from western countries. The health significance of elevated urinary Ni and its causative factors remain to be determined. [Copyright &y& Elsevier]

Abstract: Lung cancer has been the main cause of cancer-related mortality in Taiwanese women since 1986. Gradual increases in both awareness of risks and use of extractor fans in kitchens should reduce the incidence of this disease. To investigate the birth cohort effect on lung cancer incidence in Taiwanese women for 1981–1998, an age-period-cohort (APC) model analysis was employed to study the effects of age, time periods, birth cohorts and histological types of lung cancer. A significant increase in lung cancer incidence among women was found for the period 1981–1998 (r =0.96, P &#60;0.05), principally of adenocarcinoma, then squamous cell carcinoma. Age is the strongest predictor according to the APC model. The birth cohort of 1917–1926 has the highest risk of lung cancer. However, in recent cohorts, particularly those born after 1956, the incidence has fallen. The declining incidence in younger cohorts may be due to the increased use of extractor fans in kitchens reducing exposure to carcinogenic fumes from cooking oil. [Copyright &y& Elsevier]

The effect of five lignans, epi-aschantin, epi-magnolin, epi-yangambin, deoxypodophyllotoxin and yatein, isolated from Hernandia nymphaeifolia on Ca2+ signaling in Madin–Darby canine kidney cells was examined using fura-2 as a Ca2+ indicator. These lignans at concentrations between 10 and 100 μM increased [Ca2+]i in a concentration-dependent manner. Removal of extracellular Ca2+ abolished the Ca2+ signals evoked by 50 μM of the lignans. La3+(50 μM) abolished the Ca2+ signals induced by 100 μM of epi-aschantin, epi-magnolin and epi-yangambin, and 20 μM deoxypodophyllotoxin, but inhibited by 60% 50 μM yatein-induced responses. All five lignans (50–100 μM) inhibited by 42–65% thapsigargin-induced capacitative Ca2+ entry, and inhibited by 23–61% thapsigargin-induced intracellular Ca2+ release. Epi-yangambin (100 μM), epi-magnolin (100 μM), and epi-aschantin (100 μM) inhibited by 8–38% 10 μM ATP-induced Ca2+ release. Trypan blue exclusion revealed that incubation with deoxypodophyllotoxin or yatein (but not the other lignans) decreased cell viability in a concentration-dependent manner. Together, the results suggest that, in renal tubular cells, these lignans exert multiple actions on Ca2+ signaling. They caused Ca2+ influx but reduced thapsigargin-induced capacitative Ca2+ entry and also thapsigargin- and ATP-induced Ca2+ release. Additionally, deoxypodophyllotoxin and yatein may be cytotoxic. [Copyright &y& Elsevier]

Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient's specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1β expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis. [ABSTRACT FROM AUTHOR]

Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%–90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy. We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews. Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut. In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials. • Neurological mechanisms link brain reward, cognitive, and impulsive systems for BQ use. • Areca nut use increases both brain serotonin and noradrenaline levels. • Arecoline has monoamine oxidase-A inhibitor-like properties. • Antidepressant therapy has a potential effect on reduced use of BQ. • Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. [ABSTRACT FROM AUTHOR]