[Promotive excretion of causative agents of Yusho by intake of fermented brown rice with Aspergillus oryze in patients with Yusho --with regard to PCDFs and PCDDs].

Forty years have passed since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the patients with Yusho have been still suffering from several objective and subjective symptoms. In order to improve or, if possible, to cure such symptoms, the most important therapeutic treatment is considered to actively excrete the causative agents, that is, polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) from the bodies of the patients and to reduce their body burdens. In rats, chlorophyll and dietary fiber have been shown to promote the fecal excretion of PCDFs and PCDDs and to reduce their levels in rats. In this study, we have examined whether such kinds of effect are also observed by fermented brown rice with Aspergillus oryzae (FBRA) containing 5% spirulina, which is so-called spirulina HI*GENKI, the health food and relatively rich with chlorophyll and dietary fiber, in eighteen patients with Yusho. They were divided into two groups, namely group A, ten patients (3 males and 7 females) with the mean age of 67.7 years old and group B, eight patients (4 males and 4 females) with the mean age of 64.1 years old. Respective mean concentrations of the three PCDF congeners, that is, 2,3,4,7,8-PenCDF, 1, 2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF in the blood on lipid weight basis just before initiating this study were as follows; group A: 413, 152 and 45.7 pg/g lipid, and group B: 151, 42.7 and 17.3 pg/g lipid. Contamination levels of these PCDF congeners in group A were 2.6 to 3.6 times higher than those in group B. In respective mean concentrations of PCDFs, PCDDs and PCDFs/DDs in both groups were as follows; group A: 228, 30.9 and 258 pg-TEQ/g lipid, and group B: 82.4, 19.7 and 102 pg-TEQ/g lipid. Contamination levels of PCDFs and PCDDs were around 2 times higher in group A than in group B. Group A took around 7.0 g of spirulina HI*GENKI after each meal and tree times a day for the first one year and for the second one year, they did not take spirulina HI*GENKI any more. Group B took spirulina HI*GENKI with the same manner as the group A only for the second one year. The concentrations of PCDFs and PCDDs in the blood of groups A and B were also measured at the end of the first and second year, respectively. Assuming the body fat is also contaminated with PCDFs and PCDDs at their concentrations on lipid weight basis in the blood and the content of body fat is 20% of 60 kg body weight, we computed the average amounts in the net excretion of PCDFs and PCDFs/DDs from the body of the patients due to the intake of spirulina HI*GENKI in groups A and B. As a result, in group A, 85.0 and 99.6 ng-TEQ/patient, respectively were excreted from the body of the patients. In group B, only 38.1 nd 40.0 ng-TEQ/patient were excreted. Accordingly, promotive excretion of PCDFs and PCDDs from the patients with Yusho seemed much effective in group A, of which their concentrations in the blood were much higher than those of group B.

[Average of the PCDFs value in blood in patients with Yusho in the 2001 to 2003 fiscal year and comparison between the clinical features and PCDFs].

BACKGROUND: Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth, general fatigue, headaches, and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001. SUBJECTS AND METHODS: The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15 years previously. RESULTS AND DISCUSSION: The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well, the blood PeCDF level was related to PCB level, hexachlorobiphenyl level, urinary sugar, erythrocyte sedimetation rate (ESR) (2-hour), thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988. However, PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions.

[Relationship between blood dioxin levels and present/past clinical symptoms in Kanemi Yusho patients].

BACKGROUND: Kanemi Yusho was a food poisoning incident caused by rice bran oil that occurred in western Japan, particularly in northern Kyushu, in 1968. It is difficult to determine the symptoms in patients after many years since the occurrence. Techniques for measuring blood dioxins have advanced recently. More accurate data measurement has now become possible, and techniques for mass data analysis, such as data mining, have also advanced. It has also become possible to find unknown characteristics, even in an object group with elusive characteristics, by checking all the combinations in all the patients. AIM: There are already several reports on the incidence of symptoms in Yusho patients. These reports are limited to symptoms in a single period, and there has been no analysis taking into account the time that has elapsed. Here, we evaluated the relationship between recent and past symptoms and 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) levels in the same subject patient, in order to demonstrate the correlation between PeCDF levels and symptoms at a time point close to the incident. METHODS: Subjects were examined for symptoms of Yusho and had blood PeCDF levels measured, both recently and in the past. Combinations were extracted using association analysis of data mining technique for comparison, which had strong correlations between the presence or absence of symptoms in the medical examination, tests including blood test, dermatological examination, dental examination and ophthalmologic examination in recent years (2001-2004) and the blood PeCDF levels and those between the presence or absence of past (1986-1989) symptoms and recent blood PeCDF levels. RESULTS: Subjects with higher PeCDF levels were more likely to present with pigmentation, a symptom included in the diagnostic criteria for Yusho. Pigmentation was a commonly found symptom in the past. Past pigmentation was a common symptom in the present. DISCUSSION: PeCDF levels were measured recently and therefore should not be compared directly with past symptoms. However, among the symptoms included in the diagnostic criteria, past symptoms tended to have a stronger relationship with PeCDF levels than did recent symptoms. We suggest that the present PeCDF level is strongly related to the past symptoms since the present PeCDF level is correlated with the past PeCDF level due to constant emission rate. More specifically, if the past PeCDF level is strongly related to the past symptoms, it can indirectly be concluded that the present PeCDF level is also strongly related to the past symptoms. Thus, the present PeCDF level cannot be related to the past symptoms directly but can indirectly. CONCLUSIONS: Combining recent and past symptoms further demonstrated that clinical symptoms are strongly related to PeCDF toxicity. This may have resulted from the increase in symptoms with aging, however, it was demonstrated that the symptoms of each patient were relieved and become obscure.

Excretion of causative PCDFs congeners of Yusho by one year intake of FBRA in patients with Yusho.

Thirty-eight years have passed since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the patients with Yusho have been still suffering from several objective and subjective symptoms. In order to improve or, if possible, to cure the such symptoms, the most important therapeutic treatment is considered to actively excrete the causative agents, that is, polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) from the bodies of the patients and to reduce their body burdens. In rats, dietary fiber and chlorophyll have been shown to promote the fecal excretion of dioxins and to reduce their levels in rat liver. In this study, we examined whether such kinds of effect were also observed by FBRA, which was the health food and relatively rich with dietary fiber and chlorophyll, in eighteen patients with Yusho, which were divided into two groups, namely group A, ten patients (Male: 3 and Female: 7) with the mean age of 67.7 years old and group B, eight patients (Male: 4 and Female: 4) with the mean age of 64.1 years. Respective mean concentrations of the three PCDF congeners, that is, 2,3,4,7,8-PenCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF in the blood on whole weight basis just before initiating this study were as follows; group A: 1.36, 0.491 and 0.150 pg/g, and group B: 0.571, 0.159 and 0. 064 pg/g. Contamination levels of these PCDF congeners in group A were 2 to 3 times higher than those in group B. Group A took 7.0 to 10.5g of FBRA after each meal and tree times a day for the first one year and for second one year, they did not take FBRA any more. Group B took FBRA with the same manner as the group A only for the second one year. The concentrations of these PCDFs congeners in the blood of groups A and B were also measured at the end of first and second year, respectively. Assuming that the lipid content of the blood is 0.3% in order to convert their concentrations on whole weight basis to those on lipid weight basis and also that the body fat is contaminated with these PCDF congeners at their concentrations on lipid weight basis and the content of body fat is 20% of the body weight (60 kg), we computed the average amounts in the net excretion of these PCDF congeners from the body of the patients due to the intake of FBRA in groups A and B. As a result, in group A, 120, 372 and 96 ng/patient of 2,3,4,7,8-PenCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF, respectively, were excreted from the body of the patients. In group B, however, 36 ng/patient of 2,3,4,7,8-PenCDF only was excreted, but other two PCDF congeners were not. Accordingly, promotive excretion of theses PCDF congeners from the patients with Yusho seemed much effective in group A, of which their concentrations in the blood were much higher than those of group B.

Relationship between clinical features and blood levels of pentachlorodibenzofuran in patients with Yusho.

BACKGROUND: Yusho is a form of food poisoning that occurred in 1968, as a result of consuming rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins such as polychlorinated dibenzofurans (PCDFs). The victims of Yusho suffered from various dermatological, ophthalmological, and mucosal symptoms in addition to general fatigue, weight loss, anorexia, headache, paresthesia of the extremities, abdominal pain, cough and sputa, dysmenorrhea, and growth retardation in infants and children. We measured the blood levels of dioxins in the annual medical check-up of Yusho patients from 2001 to 2003. PURPOSE: To analyze the relationship between the concentrations of PCDFs/PCBs and the subjective/objective/laboratory findings of patients with Yusho. We also compared the present clinical findings with those collected in 1988. RESULTS AND DISCUSSION: The mean blood level of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in 359 patients with Yusho was 177.50 pg/g lipids, which was much higher than that of normal controls (15.2 +/- 8.9 pg/g lipids). The blood levels of PeCDF were significantly correlated with total PCB levels, hexachlorobiphenyl levels, urinary sugar, 2-h erythrocyte sedimentation rate, thymol turbidity test, and sodium levels. A significant correlation was also noted with dermatological findings (acneform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. The incidence and severity of most of the dermatological and ophthalmological symptoms decreased from 1988 to 2001-2003. In conclusion, high amounts of PCBs and PeCDF are still present in a number of patients with Yusho. The patients still suffer from various mucocutaneous and subjective symptoms.

[Evaluation of dermatological symptoms of Yusho patients in the annual examination in 2003-2004].

We evaluated the severity grades and the skin severity scores of the skin symptoms who visited the annual examinations of Fukuoka prefecture in 2003 and 2004. The severity of skin symptoms improved significantly in the first 20 years; nowadays, however, further improvement can hardly be observed. More than 36 years have passed since the Yusho incident, and about 60% of the patients currently present no skin symptoms. In contrast, in about 40% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could still be observed. Using Peason's correlation coefficient test and Spearman's correlation coefficient test, we analyzed correlation between "PCB pattern" and the blood PCB concentration, the skin severity grade and the skin severity scores. However, we could not find out any obvious correlation.

[Evaluation of dermatological symptoms of Yusho patients in the annual examination in 2001-2002].

We evaluated the severity grades and the skin severity scores of the skin symptoms of Yusho patients who visited the annual examinations in 2001 and 2002. The patients who participated in the examinations had been decreased gradually. However, because of enhancement of social interest, the number of the patients who visited the examination increased. The pattern of the severity grades and the severity scores was different from that of the past. A careful follow-up and analysis is required.