A multicenter case‐control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospital‐matched controls were included. We found a significant dose‐response relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR = 13.9) being for those who consumed more than 900 g/day‐year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8–19.7 fold and, to all 3 substances, to 41.2‐fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

Background: Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease. Methods: A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1–25 µg/mL in rat plasma (R²>0.999). Results: The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment. Conclusion: We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders.

Objectives We evaluated the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and immunological measurements using blood samples from coke oven workers exposed to high and low PAH levels. Methods A population-based cross-sectional study was conducted from 2008–2009 with coke oven workers and steel-rolling workers as the exposed and control groups, respectively. Questionnaires on basic demographic information were administered. Personal breathing zone and urine samples were collected to quantify personal PAH intake and biological response doses. Immunological and cytokine parameters in serum were analysed. Urinary malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were analysed to determine oxidative stress induced by PAHs in relation to altered humoural immunological status. Results Mean levels of serum immunoglobulin A (IgA) and TNF-α were significantly increased in coke oven workers compared to steel-rolling workers who had no or minimal PAH exposure (p=0.0033 and p252 (dibenzo(a,h)anthracene, benzo(a)pyrene, benzo(a)anthracene and/or indeno(1,2,3-cd)pyrene) correlated with IgA and IgE levels. Conclusions This study showed that coke oven workers with chronic exposure to PAHs may develop immunological alteration. Oxidative stress and lipid peroxidation induced by PAHs may partly explain the alteration in immunological parameters.