Hiroyuki Aikawa

Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure.

Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean ± SEM: male, 37.0 ± 6.1; female, 37.2 ± 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 ± 5.6; female, 70.6 ± 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.

Inhibitory effect of natural and environmental estrogens on thymic hormone production in thymus epithelial cell culture

The present study was carried out to assess the direct effect of natural estrogen and environmental estrogens on thymus epithelial cell (TEC) production/secretion of the thymic hormone thymosin-alpha 1 by using the technique of quantitative high-performance liquid chromatography. The presence of estrogen receptors in the TECs was also investigated. Murine TECs were cultured in the experimental DMEM medium containing various concentrations of natural or environmental estrogens, which was followed by determining the production of thymosin-alpha 1. The production of thymosin-alpha 1 by TECs was significantly inhibited by increasing concentrations of 17beta-estradiol (natural estrogen) over 3 x 10(-11) M, genistein (phytoestrogen) over 3 x 10(-9) M, coumestrol (phytoestrogen) over 3 x 10(-9) M, alpha-zearalanol (livestock anabolic) over 3 x 10(-7) and bisphenol-A (plastic) over 3 x 10(-6) M. Small amounts of estrogen receptor were present in the TECs. The above results clearly indicate that natural and environmental estrogens directly modulate TECs to produce thymic hormone probably through an estrogen receptor mechanism. Furthermore, our finding may be useful for evaluating biological effects of chemicals with estrogenic activity.

The Present Situation of Chronic Arsenism and Research in China

Publisher Summary Since chronic endemic arsenism was found in Taiwan in 1968, the disease has been reported in the continent of China only in recent years. Although its history is short, the situation and spread of the disease are very serious. The population exposed has been over 2 million and diagnosed arsenism patients number up to 20,000. Now the epidemic area is expanding. The chronic arsenic (As) poisoning in China can be divided into three types according to the exposure sources. One is caused by drinking water, in which the arsenic concentration is very high. The second is caused by coal burning. People use coal containing high levels of As as a fuel for cooking and drying grain in the kitchen and thus, they inhale high levels of As concentration that is in the air. The third type is caused by industry exposure, mainly copper smelting and As mining. There are about 30,000 workers in the industry exposed to As. Besides the skin changes in all three types of As poisoning, lung cancer incidence is high in coal burning and industrial exposure, especially in As mines. Another characteristic of endemic arsenism in China is that the fluoride content was also high in both drinking water and burned coal with high As concentration.

Effects of Liposome-Encapsulated Hemoglobin on Learning Ability in Tokai High-Avoider Rat After Total Brain Ischemia and Reperfusion

Liposome-encapsulated hemoglobin with low O2 -affinity (l-LEH) was shown to be protective in focal brain ischemia and reperfusion (I/R) in rats and primates. We tested l-LEH in the transient whole brain ischemia in the Tokai high-avoider rat (THA), which has been selected, mated, and bred over 77 generations for a high and consistent learning ability determined by the Sidman avoidance test (SAT). Young/naïve (before SAT) and adult/parent (after SAT) THA rats underwent acute and complete four-vessel occlusion in the chest for 3 or 5 min, administration of 2 mL/kg of l-LEH, saline, or homologous washed red blood cells (RBCs), reperfusion, and resuscitation. One week later, all rats underwent SAT, open-field behavioral observation, Morris water maze tests, and morphological study. Whereas young/naïve rats treated with l-LEH retained a rapid and consistent learning curve as in nonischemic controls, THA rats treated with RBCs or saline had retarded learning response on SAT as well as reduced cellularity in the amygdala. Adult/parent rats with established memory on SAT maintained perfect achievement even after I/R. In contrast, l-LEH-treated rats showed no better performance on Morris water maze (function) or cellularity of the CA1 sector of the hippocampus (morphology) compared with the rats treated with RBCs. Although task performance on SAT and Morris water maze appeared antithetical, morphological observations corresponded to the respective functions, suggesting that l-LEH was protective only for the amygdala on SAT tasks but not for the CA1 sector of the hippocampus on spatial orientation as in our previous studies on focal brain I/R, where the cortex was preserved better than basal ganglia.

Perceived Sleepiness of Non-Shift Working Men in Two Different Types of Work Organization

Perceived Sleepiness of Non‐Shift Working Men in Two Different Types of Work Organization: Kenji Fukasawa, et al. Department of Basic Clinical Science and Public Health, Tokai University School of Medicine—Increased sleepiness at work is increasingly being focused on as a safety and health issue. However, research on workers’ sleepiness is very limited in scope and the characteristics of work organization, including the impact of job stress, have not been fully addressed. A questionnaire survey was conducted to investigate the prevalence of daytime sleepiness and its associated factors among non‐shift working men at two manufacturing businesses: Company A, having a rapid rate of development and growth, with 564 workers (19– 61 yr old, mean age: 32.7, response rate: 81.4%); and Company B, long established, possessing a huge production facility, with 1,654 workers (20–63 yr old, mean age: 37.1, response rate: 78.2%). The prevalence of daytime sleepiness was 11.3% in company A and 16.8% in company B. Multivariate logistic regression analysis revealed that, in company A, perceived sleepiness was associated with long sleep duration on non‐working days and high cognitive demands and, in company B, with insufficient daily sleep, single, and depression. Psychosomatic exhaustion resulting from jobs requiring high adaptivity due to rapid frequency of operational change as in company A may have the potential to become an important factor in perceived sleepiness. However, in a comparatively stable work organization, as in company B, increased sleepiness may be mainly linked to factors outside work. It is suggested that not only lifestyle and sleep habits, but also the characteristics and dynamics of a work organization should be a focus of attention when planning measures to prevent sleepiness at work.

The Use of Docosahexaenoic Acid Supplementation to Ameliorate the Hyperactivity of Rat Pups Induced by in utero Ethanol Exposure

It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA with tap water (TW/n-3), (c) 5% safflower oil with 10%-EtOH (ET/n-6), (d) 3% safflower oil and 2% DHA with 10%-EtOH (ET/n-3) at gestational day (GD) 7.10%-EtOH was administered to dams in ET/n-6 and ET/n-3 groups from GD 7 to the pups’ weaning (postnatal week 4), and all pups were fed with the same diet that was given to their dams during the entire examination period. The open-field test and the water E-maze test were conducted for all pups, and a spontaneous motor activity test and the Sidman electric shock avoidance test were performed for some of male pups. Amounts of monoamine metabolites in striatum were then determined, and fatty acid analyses of total brain lipids were performed.The male pups in the ET/n-6 group showed significandy more rearing and square-crossing movements in the open-field test, and significandy higher spontaneous motor activity during the dark period in the daily cycle compared to the males in the TW/n-6 group. The male pups in the ET/n-3 group showed fewer of these behaviors in the open-field test compared to the ET/n-6 group males, and a normal pattern of spontaneous motor activity.Learning disturbance induced byin utero EtOH exposure was not observed in the E-shaped water maze, but was observed in the avoidance rates in the Sidman electric shock avoidance test. However, there was no significant modifying effect of DHA on the avoidance rates in EtOH exposed pups.The analysis of the fatty acid composition of total lipids in the brains of the pups revealed high levels of DHA in the diet reflected an increased level of brain DHA and caused a decreased level of the brain arachidonic acid. Retroco nversion from DHA to eicosapentaenoic acid was also observed. However, there was no significant effect of DHA on the levels of monoamine metabolites.These results support the hypothesis that DHA can counteract the attention deficit hyperactivity disorder.

Effects of ethyl alcohol administration to rat dams during the gestation period on learning behavior and on levels of monoamines and metabolites in rat pup brain after birth.

Pregnant rats were given 0%-, 5%-, 10%- and 20% ethyl alcohol in drinking water during the gestation period.We evaluated the brain function of pups born of alcohol-administered dams. Learning ability (Sidman avoidance behavior), the amounts of monoamines (noradrenalin, dopamine, serotonin) and metabolites (3,4-dihydroxyphenyl acetic acid [DOPAC], homovanillic acid [HVA] and 5-hydroxyindole acetic acid [5-HIAA])in whole brain were examined for neurobehavioral and neurochemical effects.There was no effect on Sidman avoidance behavior in 56-day-old offspring, but alterations of the amounts of monoamines and their metabolites were observed even in 66-day-old offspring as a result of the dams’ exposure to ethanol during pregnancy.

Changes in the amounts of neurotransmitters released from the striatum and spontaneous motor activity in rats exposed to high doses of toluene.

We studied the neurotoxicological effects of high-dose toluene exposure by measuring neurotransmitter release from the striatum and spontaneous motor activity in freemoving Tokai High Avoider (THA) male rats. The rats were exposed to 1,000, 2,000, and 4,000ppm toluene for 4 hours. During the 4-hour exposure period and each one hour pre- and post-exposure periods, acetylcholine (ACh), 3, 4-dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the microdialysate from kthe striatum of each rat were measured continuously using microdialysis. Simultaneously, spontaneous motor activity of each rat was monitored using an Aimex device. The amounts of neurotransmitters released and spontaneous motor activity showed similar changes for every concentration of toluene exposure during those periods. Although minimal changes in neurotransmitters and motor activity were observed in the 1,000 ppm group, increases in neurotransmitter release and motor activity were observed in the 2,000 ppm group during the entire exposure period and also in the 4,000 ppm group during the early period of exposure. On the other hand, decreases in neurotransmitter release and motor activity were observed in the 4,000 ppm group during the late period of exposure. These findings indicate that the striatum influences motor activity via changes in the amounts of neurotransmitters released during the period of high-dose toluene exposure.

Natural and environmental oestrogens increase expression of SS-A/Ro autoantigen in the salivary gland of ovariectomized immature rats

Abstract SS-A/Ro autoantibodies are detected at high levels in patients with autoimmune diseases such as Sjogren’s syndrome. It has been reported that natural oestrogen is capable of inducing cell surface expression of SS-A/Ro autoantigens in salivary glands. We analyzed the effect of environmental oestrogens (i.e. oestrogenic xenobiotics) on the expression of the 52 kDa SS-A/Ro autoantigen in the rat salivary gland by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Plant- or plastic-derived environmental oestrogens induced up to approximately 3.5-fold increase in 52 kDa SS-A/Ro mRNA levels in rat salivary gland compared to levels in untreated animals. The ISH results paralleled the RT-PCR results. These findings suggest that environmental oestrogen stimulation can induce the expression of autoantigens such as SS-A/Ro.

INVESTIGATION OF 6 CASES OF MALIGNANT GASTRIC LYMPHOMA

We experienced 6 cases of malignant gastric lymphoma during the 5 years from January 1984 to December 1988. In 2 of the 6 patients gastric excision and chemotherapy regimen were performed prolonged their lives for long periods, but the remaining 4 merely underwent chemotherapy. Unexpectedly, favorable result of a long survival could be obtained for the latter cases, as well as for the fomers of the said gastric excision, except for one case which died of other illness.