Environmental Health and Preventive Medicine

Mucosal immunity plays a pivotal role for body defense against infection and allergy. The aim of this study was to clarify the effects of 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on mucosal immunity in the gut. Fecal IgA level and oral tolerance induction were examined in TCDD-treated mice. Flow cytometric and histological analyses were also performed. Single oral administration of low dose 2,3,7,8-TCDD resulted in a marked decrease in IgA secretion in the gut without any effects on the cellular components of gut-associated lymphoid tissues (GALT) including Peyer’s patches (PPs) and mesenteric lymph nodes (LNs). Decressed IgA secretion by TCDD was not observed in aryl hydrocarbon receptor (AhR)-deficient mice. Flow cytometric analysis revealed that IgA B cells in PPs and the mesenteric LNs remained unchanged in the TCDD-treated mice. An immunofluorescence study also demonstrated that a significant number of cytoplasmic IgA cells were present in the lamina propria of the gut in the TCDD-treated mice. Furthermore, oral tolerance induction by ovalbumin (OVA) was impaired in the TCDD-treated mice and OVA-specific T cell proliferation occurred in the peripheral lymphoid tissues including the spleen and LNs. These results suggest that a relatively low dose of TCDD impairs mucosal immunity in the gut and induces systemic sensitization by oral antigens.

Because serum transaminases elevate alcohol dose dependently as a consequence of liver injury, they serve as useful biological markers of excessive drinking. However, these markers are inadequate in individuals with a defective allele of the aldehyde dehydrogenase 2 gene, ALDH2*2, because they show a different correlation with the amount of ethanol. For example, the serum alanine aminotransferase (ALT) level could become even lower than the baseline after alcohol intake in ALDH2*2 carriers. In fact, multiple studies suggest that ALDH2*2 is a hepato-protective factor in healthy individuals. Importantly, excessive drinking is particularly dangerous in carriers of ALDH2*2 because the risk of alcohol-related cancer is much higher than that for ALDH2*1/*1 carriers. Without recognizing the genotype interaction on serum transaminase, the opportunity to warn people about potential cancer risks is missed owing to incorrect interpretation. This is particularly important in East Asian countries where approximately half of the population carries the ALDH2*2 allele. To date, the mechanism of liver protection from ethanol load in individuals with ALDH2*2 has not been fully elucidated. However, some reasonable mechanisms have been suggested by experimental studies, including remodelling of detoxifying systems. Further studies to uncover the whole mechanism are anticipated.

There are several reports of cellular-aging-dependent alterations in the antioxidant capacity of human fibroblasts. Fibroblasts show slower the growth rate at late passages (referred to hereafter as old cells) than at early passages (referred to hereafter as young cells). Antioxidants may control cellular growth by modulating reactive oxygen species (ROS). Methanolic extracts from broad beans (MEBB) contain phenolic compounds and have ROS-scavenging activities. In this study, we investigated the effects of MEBB on cellular growth and antioxidant levels in normal human lung fibroblasts. To determine cytosolic superoxide dismutase (SOD) activities, cytosolic glutathione peroxidase (GSH-Px) activities, catalase activities, reduced glutathione (GSH) concentrations, and growth rate, MEBB treatments were performed on young and old cells. In young and old cells treated with 120 μg/ml MEBB, the growth rates increased by 28.1 and 15.2%, respectively, compared with controls. The MEBB treatment of young cells caused a 62.5% increase in SOD activity, but the treatment of old cells caused a 39.5% decrease. The catalase activities of the young and old cells treated with MEBB were equal to those of control cells. Young and old cells treated with MEBB were equal to the control cells in terms of GSH-Px activity. The GSH concentrations in the young and old cells treated with 120 μg/ml MEBB increased by 22.1 and 45.9%, respectively. These studies elucidated a new cellular growth mechanism whereby human lung fibroblasts modulate intracellular GSH levels via the action of MEBB.

Prevalence of age-dependent diseases such as asthma is confounded not only by aging effects but also by cohort and period effects. Age-period-cohort (APC) analysis is commonly performed to isolate the effects of these three factors from two-way tables of prevalence by age and birth cohort. However, APC analysis suffers from technical difficulties such as non-identifiability problems. We isolated the effects of these three factors in a step-by-step manner by analyzing Japan’s school health data collected from 1984 to 2004 focusing on asthma prevalence among school children aged 6–17 years consisting of 30 birth cohorts (entering classes). We verified the accuracy of our method showing high agreement of the observed age-, period- and cohort-specific data and the data predicted by our method. The aging effects were found to follow cubic equations whose multinomial coefficients were determined by an optimization technique. The obtained aging effect curves of age-specific asthma prevalence showed that boys reach the peak prevalence at 13 and girls at 14, declining markedly afterward. The cohort effects, defined as the arithmetic asthma prevalence means for ages 6–17 years, showed consistent upward trends for the 30 birth cohorts born in 1968–97 for both sexes. The period effects showed a consistent decline since 1984 but abruptly increased in 1999 and then declined again. We were not able to identify the exact cause of the increase in 1999, therefore, this should be examined in the future studies. Because the cohort effects show no sign of leveling off yet, asthma prevalence will likely increase in the foreseeable future.

All residents aged 65 or over in a rural city (n=5340) were studied with a self-administered questionnaire on psychiatric symptoms, physical health status, medical history, and environmental factors. After the screening, the clinical diagnosis of senile dementia was made by psychiatrists. The overall prevalence was 4.0% among responders staying at home (201/4969). The prevalence increased with age for both males and females and tended to be higher for females than males. The multilogistic analysis of the above variables showed that in the cerebrovascular type, stroke and inactive physical status might be risk factors for both gender groups. For the Alzheimer’s type, age and inactive physical status might be risk factors. For overall dementia, age, stroke, and inactive physical status might be risk factors.

Mennonites reside in clusters, do not use modern sewage systems and consume water from non-municipal sources. The purpose of this study is to assess risk of Escherichia coli exposure via consumption of non-municipal waters in Mennonite versus non-Mennonite rural households. Results were reviewed for non-municipal water samples collected by the local health department from Mennonite and non-Mennonite lifestyle households from 1998 through 2012. Water contamination was examined with the help of two study variables: water quality (potable, polluted) and gastrointestinal (GI) health risk (none, low, high). These variables were analyzed for association with lifestyle (Mennonite, non-Mennonite) and season (fall, winter, spring, summer) of sample collection. Data were split into two periods to adjust for the ceiling effect of laboratory instrument. From the entire cohort, 82 % samples were polluted and 46 % samples contained E. coli, which is consistent with high GI health risk. In recent years (2009 through 2012), the presence of total coliforms was higher in non-Mennonites (39 %, P = 0.018) and presence of E. coli was higher in Mennonites (P = 0.012). Most polluted samples were collected during summer (45 %, P = 0.019) and had high GI health risk (51 %, P = 0.008) as compared to other seasons. Majority of non-municipal waters in this region are polluted, consuming those poses a high GI health risk and contamination is prevalent in all households consuming these waters. An association of E. coli exposure with the Mennonite lifestyle was limited to recent years. Seasons with high heat index and increased surface runoffs were the riskiest to consume non-municipal waters.

We observed acute toxicity, delayed neurotoxicity, disappearance of leptophos from tisuues and biochemical changes in four groups of hens: a group given only 30 mg/kg leptophos (iv) as the ‘leptophos group’, two groups given a treatment of 30 mg/kg phenylmethylsulfonyl fluoride (PMSF) (sc) 24 hr prior to (as the ‘pretreated group’) and following (as the ‘posttreated group’) administration of the same dose of leptophos as the leptophos group, and a group given a vehicle only as the ‘control group’. All groups other than the control group showed acute toxicity. The scores for organophosphate-induced delayed neurotoxicity (OPIDN) in the posttreated group reached the maximal level on the 16th day after leptophos administration and those in the leptophos group reached the maximal level on the 25th day. Serum acid phosphatase (AcP) activities in the leptophos group and the posttreated group were significantly lower than that in the control group (p<0.05) on the 6th day after leptophos administration and then recovered to the normal level on the 15th day. In these two groups, serum creatine phosphokinase (CPK) activity was significantly higher (p<0.01) and the concentration of serum Ca2+ was significantly lower (p<0.05) than in the control group on the 15th day after leptophos administration. Serum leucine aminopeptidase (LAP) activity in the posttreated group was significantly lower than that in the control group (p<0.01). As for the significant changes by time interval between the 6th and the 15th days after leptophos administration, CPK activity was elevated and serum Ca2+ reduced in both the leptophos group and the posttreated group, and LAP activity was also reduced in the posttreated group. The courses of leptophos disappearance in several tissues of these hens were similar in the 3 groups. These results suggest that the treatment by PMSF prior to or following the administration of leptophos can significantly modify not only clinical signs of OPIDN but also changes of several biochemical indices accompanied by OPIDN. Furthermore, it is possible to expect that these biochemical indices can provide some valuable clues for exploring the modification of OPIDN by PMSF treatment.