RESUMEN
Mutations in RAS and BRAF are predictors of the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in patients with metastatic colorectal cancer (mCRC). Therefore, simple, rapid, cost-effective methods to detect these mutations in the clinical setting are greatly needed. In the present study, we evaluated BNA Real-time PCR Mutation Detection Kit Extended RAS (BNA Real-time PCR), a real-time PCR method that uses bridged nucleic acid clamping technology to rapidly detect mutations in RAS exons 2-4 and BRAF exon 15. Genomic DNA was extracted from 54 formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from mCRC patients. Among the 54 FFPE samples, BNA Real-time PCR detected 21 RAS mutations (38.9%) and 5 BRAF mutations (9.3%), and the reference assay (KRAS Mutation Detection Kit and MEBGEN™ RASKET KIT) detected 22 RAS mutations (40.7%). The concordance rate of detected RAS mutations between the BNA Real-time PCR assay and the reference assays was 98.2% (53/54). The BNA Real-time PCR assay proved to be a more simple, rapid, and cost-effective method for detecting KRAS and RAS mutations compared with existing assays. These findings suggest that BNA Real-time PCR is a valuable tool for predicting the efficacy of early anti-EGFR therapy in mCRC patients.
Asunto(s)
Neoplasias Colorrectales/genética , Análisis Mutacional de ADN/métodos , ADN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas ras/genética , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Factores de TiempoRESUMEN
In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but also polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. We previously measured dioxins concentrations in the blood of 854 Yusho patients by annual medical examination from 2001 to 2013. We determined the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than double those of normal controls. In 2012, a new Yusho criteria was established. Family members living with a Yusho patient were also certified as Yusho patients and called Yusho family cohabitant patients. In this study, we compared the distribution of 2,3,4,7,8-PeCDF concentration in the blood of Yusho patients and Yusho family cohabitant patients. It was suspected that the distribution of 2,3,4,7,8-PeCDF concentration in Yusho family cohabitant patients would be lower than that of Yusho patients.
Asunto(s)
Dioxinas/sangre , Porfirias/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hydroxylated polychlorinated biphenyls (OH-PCBs) are well known as metabolites of PCBs in the human body. We improved a measurement method for OH-PCBs in blood samples using LC/MS/MS. A new 2 microm particle column was used, and the analytical conditions for the LC/MS/MS measurements were optimized. The improved method is more sensitive than the conventional method for 5g blood samples. And, this method is effective at determining the concentrations of OH-PCBs, PCBs and dioxins from the same sample without special treatment of the sample such as derivatization.
Asunto(s)
Bifenilos Policlorados/sangre , Técnicas de Química Analítica/métodos , Cromatografía Liquida , Humanos , Hidroxilación , Espectrometría de Masas en TándemRESUMEN
Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We measured the concentration of OH-PCBs in blood collected from 183 Yusho patients living in Japan in 2010. The major OH-PCB metabolites were 4-OH-CB187 (ND-1300 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (8.4-1200 pg/g-wet), 4-OH-CB109 (ND-530 pg/g-wet) and 4'-OH-CB172 (ND-380 pg/g-wet). The total OH-PCBs ranged from 36 to 3800 pg/g-wet. A positive relationship between the concentrations of OH-PCBs and PCBs was observed, but no significant relationship between the concentrations of OH-PCBs and PCDD/DFs was observed.
Asunto(s)
Bifenilos Policlorados/sangre , Porfirias/sangre , Humanos , Hidroxilación , JapónRESUMEN
We compared concentrations of PCB congeners between conventional 80 degrees C alkali digestion method and 30 degrees C alkali digestion method using 22 individual blood samples collected during 2009 annual Yusho examinations. The mean concentration of tri-CB in 30 degrees C alkali digestion method was lower than that of conventional method. However, concentration of total PCBs, 2,3',4,4',5-pentaCB (PCB118), 2,2',4,4',5,5'-hexaCB (PCB153) and 2,3,3',4,4', 5-hexaCB (PCB156), which were used as index for Yusho diagnosis, were equivalent between the methods. It was considered that the 30 degrees C alkali digestion method was available for blood PCB congener specific analysis in Yusho diagnosis.
Asunto(s)
Bifenilos Policlorados/sangre , Álcalis , Técnicas de Química Analítica/métodos , Isomerismo , Bifenilos Policlorados/química , TemperaturaRESUMEN
We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs), and non-dioxin-like PCBs in paired samples of blood and breast milk collected from 67 secundiparas in Sapporo City, Japan, and combined this data with those of the 30 secundiparas previously measured. The arithmetic mean total toxic equivalents (TEQ-WHO) concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of the 97 secundiparous subjects were 3.0-23 (mean: 13, median: 14) and 2.7-20 (mean: 8.6, median: 8.5) pg TEQ g(-1) lipid, respectively. The sums of the concentrations of 56 non-dioxin-like PCB congeners that were measured in the subjects' blood and breast milk were 16-326 (mean: 107, median: 100) and 12-252 (mean: 73, median: 67) ng g(-1) lipid, respectively. The partitioning ratios of individual congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs from blood to breast milk in secundiparas were almost the same as those of primiparas that have been recently reported, suggesting that the partitioning ratios of these compounds from maternal blood to breast milk in women is little affected by delivery. Furthermore, the partition of PCB congeners with chlorine at the 2-, 3-, 4'-, and 5-positions or the 2-, 4-, 4'-, and 5-positions of the biphenyl ring from the blood to the breast milk tended to occur at a higher level than that of other congeners. In particular, the levels of tetraCB-74 and hexaCB-146 in the breast milk for both primiparous and secundiparous mothers were slightly higher than those in the blood.
Asunto(s)
Benzofuranos/sangre , Leche Humana/química , Bifenilos Policlorados/sangre , Dibenzodioxinas Policloradas/análogos & derivados , Adulto , Estudios de Cohortes , Dibenzofuranos Policlorados , Femenino , Humanos , Japón , Dibenzodioxinas Policloradas/sangre , EmbarazoRESUMEN
There is a dearth of information on the temporal changes in polychlorinated dibenzodioxin/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) contamination, in both environmental and biological specimens, in China. We compared the concentrations of PCDD/Fs and dl-PCBs in human milk collected in Shijiazhuang, Hebei Province, in northern China in 2002 (n=30) and 2007 (n=20). The level of PCDD/Fs and dl-PCBs showed an increasing trend. The mean concentrations of PCDD/Fs plus dl-PCBs were 4.47 TEQ pg g(-1) fat and 6.24 TEQ pg g(-1) fat in human milk from Shijiazhuang in 2002 and in 2007, respectively. Based on statistical analysis of questionnaire data collected by in-person interviews with mothers, we found positive correlations between consumption of sea fish and PCDFs. The PCDDs, PCDFs, PCDD/Fs, and PCDD/Fs plus dl-PCBs levels in individuals consuming greater amounts of sea fish were higher than those consuming less sea fish, both with and without adjustments for potential confounding factors. Among 17 congeners of PCDD/Fs, the 2,3,7,8-TCDF, 1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 2,3,4,6,7,8-HxCDF congener concentrations in 2007 increased 134%, 55%, 53%, 57%, 65% and 130% when compared to 2002 levels, respectively. The 2007 dl-PCB congener levels were greater than those of the 2002 samples, with the exception of PCB81 and PCB77. Specifically, PCB105, PCB114, PCB118, PCB123 and PCB156 had increased greater than twofold from 2002 to 2007. Continuous surveillance of PCDD/F and dl-PCB levels in human milk is needed to accurately evaluate both environmental contamination and the human health risk to neonates in China.
Asunto(s)
Benzofuranos/análisis , Leche Humana/química , Bifenilos Policlorados/análisis , Dibenzodioxinas Policloradas/análogos & derivados , Adulto , China , Dibenzofuranos Policlorados , Dieta , Femenino , Humanos , Entrevistas como Asunto , Estudios Longitudinales , Dibenzodioxinas Policloradas/análisis , Análisis de Componente Principal , Factores de Riesgo , Alimentos Marinos/análisis , Encuestas y CuestionariosRESUMEN
Forty two years have passed since the outbreak of Kanemi rice oil poisoning, namely, Yusho in the western Japan. However, even now the Yusho patients 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) 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 polychlorinated dibenzo-p-dioxins (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 Yusho patients. 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. Among the patients of group A, three patients were especially highly contaminated with PCDFs and we classified them into group A (High). Respective mean concentrations of PCDFs in the blood just before initiating this study were as follows; group A : 145 pg/g lipid, group A (High) : 371 pg/g lipid and group B : 52.1 pg/g lipid. Contamination levels of PCDFs, PCDDs and dioxin-like polychlorinated biphenyls (PCBs) in group A (High) were 1.7 to 2.6 times higher than those in group A and 2.4 to 7.1 times higher than those in group B. Accordingly, concentrations of dioxins (PCDFs + PCDDs + dioxin-like PCBs) in the blood of groups A, A (High) and B were, respectively, 194, 458 and 85 pg-TEQ/g lipid. Concentrations of PCBs were also the highest in group A (High) : 1399 ng/g lipid, in group A : 748 ng/g lipid and the lowest in group B : 456 ng/g lipid. Groups A and A (High) took around 7.0 g of spirulina HI * GENKI after each meal and three times a day for the first one year and for the second one year, they did not take spirulina HI * GENKI anymore. Group B took spirulina HI * GENKI with the same manner as the group A only for the second one year. The concentrations of PCDFs, PCDDs, dioxin-like PCBs and PCBs in the blood were also measured at the end of the first and second year, respectively. Assuming the body fat is also contaminated with these compounds 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 their net excretion from the body of the patients due to spirulina HI * GENKI in the three groups. As a result, in group A (High), 341 ng-TEQ/patient of dioxins was excreted from the body, which was 3.4 times greater than that in group A and 12 times higher than that in group B. Therefore, promotive excretions of causative agents of Yusho were the most effective in group A (High) and we consider spirulina HI * GENKI is more effective from the therapeutic point of view in more highly contaminated Yusho patients.
Asunto(s)
Benzofuranos/metabolismo , Benzofuranos/envenenamiento , Contaminación de Alimentos , Alimentos Orgánicos , Oryza/envenenamiento , Aceites de Plantas/envenenamiento , Anciano , Aspergillus oryzae , Benzofuranos/sangre , Carga Corporal (Radioterapia) , Dibenzofuranos Policlorados , Fibras de la Dieta/uso terapéutico , Femenino , Fermentación , Humanos , Masculino , Persona de Mediana Edad , Bifenilos Policlorados/metabolismo , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/metabolismoRESUMEN
In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. Extensive studies have been performed since 1995 by the Yusho study group involving follow-up surveys of human blood concentrations of the casual compounds in Yusho patients as well as clinical trials of the acceleration of the excretion of these compounds in Yusho patients. We have previously measured dioxin concentrations in the blood of 649 Yusho patients in annual medical examinations from 2001 to 2009. We determined that the concentrations of 2,3,4,7,8-PeCDF 1,2,3,4,7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than twice as high levels to as those of normal controls. In this study, we compared the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of male Yusho patients with those of female Yusho patients. As a result, it was found that the mean concentrations of 2,3,4,7,8-PeCDF 1,2,3,4, 7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in female Yusho patients were 2.9, 3.7, 2.4, and 1.3 times higher, respectively, than those of male Yusho patients.
Asunto(s)
Dioxinas/sangre , Contaminación de Alimentos , Oryza/envenenamiento , Aceites de Plantas/envenenamiento , Bifenilos Policlorados/envenenamiento , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
The polychlorinated quaterphenyl (PCQ) concentrations in blood are important discriminative parameters in yusho patient. In this study, a rapid analytical method for PCQ using different diameter capillary column (rapid-Rtx65TG) with high-resolution gas chromatograph high-resolution mass spectrometer (HRGC/HRMS) instead of the gas chromatograph electron capture detector (ECD/GC) was developed. Using different diameter capillary columns, the analysis time of the HRGC/HRMS was drastically shortened, and the detection sensitivity was improved. In the rapid-Rtx65TG column, a small-bore capillary column (length 1m, I.D. 0.1mm) was connected with the inlet side of the GC, and behind that column, a large-bore capillary column (length 15mm, I.D. 0.53mm) for octadecachloroquaterphenyl (ODCQ) analysis was connected. In the HRGC/HRMS measurement of ODCQ by the rapid-Rtx65TG column, the minimum limit of detection for the apparatus was 0.4 pg, and the minimum limit of determination for the blood was 0.008 ppb. On ECD/GC in the conventional method and HRGC/HRMS in this study, the PCQ concentration in blood including yusho patients and yusho suspected persons was almost equivalent.
Asunto(s)
Clorobencenos/sangre , Cromatografía de Gases y Espectrometría de Masas/métodos , Contaminación de Alimentos , Cromatografía de Gases y Espectrometría de Masas/instrumentación , Humanos , Oryza/envenenamiento , Aceites de Plantas/envenenamiento , Bifenilos Policlorados/envenenamientoRESUMEN
Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We developed a measurement method for OH-PCBs in blood samples by LC/MS/MS. This method is effective at determining the concentrations of PCDDs, PCDFs, Co-PCBs and OH-PCBs from the same sample without special treatment of the sample. The concentration of OH-PCBs in the blood of Yusho patients was examined using this method. The major OH-PCB metabolites were 4-OH-CB187 (54-906 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (32-527 pg/g-wet), 4-OH-CB109 (ND-229 pg/g-wet) and 4'-OH-CB172 (ND-143 pg/g-wet). The total OH-PCBs ranged from 95 to 1740 pg/g-wet.
Asunto(s)
Cromatografía Liquida , Oryza/envenenamiento , Aceites de Plantas/envenenamiento , Bifenilos Policlorados/sangre , Bifenilos Policlorados/envenenamiento , Espectrometría de Masas en Tándem , Contaminación de Alimentos , Humanos , HidroxilaciónRESUMEN
We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs), and non-dioxin-like PCBs in paired samples of blood and breast milk collected from 89 primiparous mothers in Sapporo City, Japan, and studied the relationships of these compounds between blood and breast milk for these women plus 30 primiparous mothers in whom these data had been previously reported. The present study is one of the few studies in which the concentration distributions of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs have been investigated in blood and breast milk collected from the same mothers. The arithmetic mean TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of these 119 subjects were 8.2, 2.9, 5.1, and 0.4 pg TEQ g(-1)lipid, respectively, and 4.8, 2.0, 4.0, and 0.4 pg TEQ g(-1)lipid, respectively, with the total TEQ concentrations of these dioxin-like compounds being 7.0-36 (mean: 17, median: 14) and 5.7-41 (mean: 11, median: 10) pg TEQ g(-1)lipid, respectively. The sums of the concentrations of 56 non-dioxin-like PCB congeners that were measured in the subjects' blood and breast milk were 43-445 (mean: 120, median: 106) and 34-366 (mean: 90, median: 81) ng g(-1)lipid, respectively, indicating that the total TEQ concentration and the total concentration of 56 non-dioxin-like PCB congeners in the maternal blood were notably higher than those in the breast milk. Statistically significant correlations were observed between maternal age and the total TEQ concentration of PCDDs, PCDFs, and dioxin-like PCBs or the total concentration of 56 non-dioxin-like PCB congeners in maternal blood, and significant correlations were also observed between maternal age and the total TEQ concentration of these dioxin-like compounds or the total concentration of 56 PCB congeners in breast milk. The total TEQ concentration of PCDDs, PCDFs, and dioxin-like PCBs in maternal blood showed a close correlation to that in subjects' breast milk, and there was also good correlation between the total concentration of 56 non-dioxin-like PCB congeners in maternal blood and that in subjects' breast milk. Pearson and Spearman correlation analyses showed a relationship between the total TEQ concentration of PCDDs, PCDFs, and dioxin-like PCBs and the total concentration of 56 non-dioxin-like PCB congeners in maternal blood, and also showed an association between the total TEQ concentration of these dioxin-like compounds and the total concentration of 56 PCB congeners in breast milk. The concentration of hexaCB-153 in maternal blood showed significant correlations to the total TEQ concentration of PCDDs, PCDFs, and dioxin-like PCBs or the total concentration of 56 non-dioxin-like PCBs in that sample. Moreover, the concentration of hexaCB-153 in breast milk also showed significant correlations to the total TEQ concentration of these dioxin-like compounds or the total concentration of 56 PCB congeners in that sample. These findings suggested that hexaCB-153 may be an indicator of total TEQ concentrations of PCDDs, PCDFs, and dioxin-like PCBs and total concentrations of 56 non-dioxin-like PCB congeners in blood and breast milk of primiparous mothers.
Asunto(s)
Benzofuranos/análisis , Leche Humana/química , Bifenilos Policlorados/análisis , Dibenzodioxinas Policloradas/análogos & derivados , Polímeros/análisis , Adulto , Benzofuranos/sangre , Benzofuranos/química , Femenino , Humanos , Exposición Materna , Bifenilos Policlorados/sangre , Bifenilos Policlorados/química , Dibenzodioxinas Policloradas/análisis , Dibenzodioxinas Policloradas/sangre , Dibenzodioxinas Policloradas/química , Polímeros/químicaRESUMEN
Effects of hypoxic solution (O(2) tension, 161 +/- 11 mmHg) on electrical responses of the membrane (slow waves), intracellular Ca(2+)-responses measured by Fura-2 fluorescence (Ca-transients) and isometric mechanical responses (phasic contraction) were observed in circular smooth muscles isolated from the guinea-pig stomach antrum. In normoxic solution (O(2) tension, 362 +/- 28 mmHg), muscle cells generated slow waves spontaneously, and switching to hypoxic solution caused an increase in frequency and decrease in duration of slow waves, with no significant change in the resting membrane potential. Hypoxia also reduced the amplitude and duration and increased the frequency of Ca-transients. The increase in frequency of slow waves by hypoxia was prevented by cyclopiazonic acid (CPA) but not by carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), potassium cyanide (KCN) or low-Ca solution. The reduction by hypoxia of the duration of slow waves was prevented by CCCP or KCN but not by CPA or low-Ca solution. Hypoxia resulted in an increase in frequency and decrease in amplitude of phasic contractions, and the changes were prevented by CPA but not by CCCP. These results suggested that in antrum smooth muscle tissues, the increase in frequency of spontaneous activity by hypoxia is related to the enhanced function of the CPA-sensitive internal Ca-stores in pacemaker cells, while the inhibition in amplitude of phasic contractions by hypoxia may be mainly related to the decrease in Ca(2+) release from the CPA-sensitive internal stores in smooth muscle cells. It is concluded that in hypoxic solution, the function of internal Ca(2+) stores is enhanced in ICC-MY and is inhibited in smooth muscle cells in the guinea-pig stomach antrum.
Asunto(s)
Hipoxia/fisiopatología , Miocitos del Músculo Liso/fisiología , Antro Pilórico/fisiología , Animales , Calcio/administración & dosificación , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Carbonil Cianuro m-Clorofenil Hidrazona/farmacología , Fenómenos Electrofisiológicos/efectos de los fármacos , Fura-2 , Cobayas , Indoles/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Cianuro de Potasio/farmacología , Antro Pilórico/efectos de los fármacosRESUMEN
To elucidate the exposure levels of polychlorinated biphenyls (PCBs) for Yusho patients, we conducted a congener-specific analysis of polychlorinated biphenyls (PCBs) in blood collected from 242, 237, 300, and 96 Yusho patients during medical check-ups performed from 2004 to 2007, respectively, and in samples from 74, 113, 125, and 148 Yusho-suspected persons during those same years, respectively, and compared the individual congener concentrations of PCBs among the groups of Yusho patients, Yusho-suspected persons, and normal controls with the concentrations previously reported. Among the 209 PCB congeners, 8 congeners of mono-ortho PCBs and 56 congeners of non-dioxin-like PCBs were identified in the blood of Yusho patients and Yusho-suspected persons. Among the PCB congeners measured in the present study, hexaCB-153, hexaCB-138, heptaCB-180, and heptaCB-182/heptaCB-187 showed high ratios to total concentrations of 64 PCB congeners detected in the blood of Yusho patients and Yusho-suspected persons from 2004 to 2007, and the profiles of the major congeners were the same as those obtained in normal controls. With respect to the minor congeners of PCBs, several differences were observed among the three groups. The sums of the concentrations of 64 PCB congeners in the blood of Yusho patients from 2004 to 2007 were 645, 760, 667, and 510 ng g(-1) lipid for each year, respectively, and the concentrations were 1.5, 1.8, 1.5, and 1.2 times higher than those of normal controls for each year, respectively. Those of the Yusho-suspected persons were approximately 0.8, 1.1, 0.9, and 1.0 times higher than those of normal controls for each year, respectively. The ratios of heptachlorinated biphenyls (heptaCBs) to the total concentrations of 64 PCB congeners in the blood of Yusho patients and Yusho-suspected persons from 2004 to 2007 tended to be slightly higher than those in the normal controls. From the results comparing the concentrations of 64 PCB congeners in the blood between Yusho patients and normal controls, the concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 for Yusho patients were 3.4, 3.8, 3.9, and 3.8 times, respectively, 3.9, 4.1, 3.9, and 4.4 times, respectively, 3.6, 3.9, 5.0, and 4.1 times, respectively, and 2.3, 2.5, 2.7, and 2.9 times higher than those of the normal controls for each year from 2004 to 2007, respectively. These results indicated that Yusho patients still have higher concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 in their blood than do unaffected people, even though over 35 years have passed since the outbreak of Yusho. These four congeners can therefore be considered to be the most important congeners for evaluating the PCBs exposure of Yusho patients.
Asunto(s)
Dioxinas/envenenamiento , Contaminación de Alimentos , Bifenilos Policlorados/sangre , Bifenilos Policlorados/envenenamiento , Anciano , Humanos , Persona de Mediana Edad , Examen FísicoRESUMEN
Dioxins are known as endocrine disrupters and widespread environmental contaminants. They are bioaccumulated in the human body. In this study, we determined concentrations of dioxins (PCDD, PCDF, Non-ortho PCB and Mono-ortho PCB) in eighteen umbilical cords provided by twelve mothers of Yusho patients and twelve umbilical cords provided by ten mothers of normal controls. The average concentrations of PCDD, PCDF, Non-ortho PCB, Mono-ortho PCB and total dioxins (PCDD/ F + Dioxin-like PCB) in the umbilical cords of Yusho patients and normal controls were 0.55, 4.55, 0.08, 0.08 and 5.26 pg-TEQ/g, respectively, and 0.50, 0.11, 0.03, 0.02 and 0.66 pg-TEQ/g, respectively. Total dioxins and PCDF concentrations in the umbilical cords of Yusho patient were about 8 and 40 times higher than those in the umbilical cords of normal controls, respectively. The average concentration of 2,3,4,7,8-PeCDF in the umbilical cords of Yusho patients was 10 pg/g. We couldn't detect 2,3,4,7, 8-PeCDF in the umbilical cords of normal controls. We suspected the 2,3,4,7,8-PeCDF concentrations in the mothers' blood were related to the 2,3,4,7,8-PeCDF concentrations in umbilical cords.
Asunto(s)
Dioxinas/análisis , Dioxinas/envenenamiento , Contaminación de Alimentos , Bifenilos Policlorados/envenenamiento , Cordón Umbilical/química , Femenino , Humanos , EmbarazoRESUMEN
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.
Asunto(s)
Aspergillus oryzae , Benzofuranos/metabolismo , Suplementos Dietéticos , Dioxinas/envenenamiento , Contaminantes Ambientales/metabolismo , Contaminación de Alimentos , Oryza , Bifenilos Policlorados/envenenamiento , Dibenzodioxinas Policloradas/análogos & derivados , Animales , Dibenzofuranos Policlorados , Fibras de la Dieta/uso terapéutico , Femenino , Fermentación , Humanos , Masculino , Persona de Mediana Edad , Dibenzodioxinas Policloradas/metabolismo , Ratas , SpirulinaRESUMEN
We conducted a congener-specific analysis of polychlorinated biphenyls (PCBs) in blood collected from 242 Yusho patients (mean: 65.5 years, median: 67.0 years) and 74 Yusho-suspected persons (mean: 54.7 years, median: 55.0 years) in 2004, and compared each congener concentrations of PCBs among the groups of Yusho patients, Yusho-suspected persons, and normal controls (mean: 68.1 years, median: 67.0 years) with the concentrations previously reported. Among the 209 PCB congeners, 8 congeners of mono-ortho PCBs and 56 congeners of non-dioxin-like PCBs were identified in the blood of Yusho patients and Yusho-suspected persons. Among the PCB congeners measured in the present study, hexaCB-153, hexaCB-138, heptaCB-180, and heptaCB-182/heptaCB-187 showed high ratios to total concentrations of 64 PCB congeners detected in the blood of Yusho patients and Yusho-suspected persons, and the congener profiles were the same as those obtained in normal controls. The sums of the concentrations of 64 PCB congeners in the blood of Yusho patients and Yusho-suspected persons were 40-3032 (mean: 645, median: 536) and 20-1418 (mean: 355, median: 317) ng g(-1) lipid, respectively, and the concentrations were 50% higher and 20% lower than those of normal controls, respectively. The relative contribution ratios of the concentrations of the triCBs, tetraCBs, and pentaCBs to the total concentrations of 64 PCB congeners in the blood of Yusho patients were slightly lower than those of Yusho-suspected persons and normal controls, and the ratios of nonaCBs and decaCB-209 concentrations were nearly the same among the Yusho patients, Yusho-suspected persons, and normal controls. However, the ratios of the concentrations of hexaCBs, heptaCBs, and octaCBs to the total concentrations of 64 PCB congeners in the blood of Yusho patients tended to be slightly higher compared to those of the Yusho-suspected persons and normal controls. From the results comparing the concentrations of 64 PCB congeners in the blood between Yusho patients and normal controls, the concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 of the Yusho patients were 3.4, 3.8, 3.9, and 3.8 times higher than those of the normal controls, respectively, indicating that even now, 35 years after exposure, Yusho patients still have a higher concentration of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 in their blood than do unaffected people. These four congeners may be considered the most important congeners for evaluating the PCBs toxicity of Yusho patients.
Asunto(s)
Contaminantes Ambientales/sangre , Bifenilos Policlorados/sangre , Distribución por Edad , Anciano , Contaminantes Ambientales/química , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Bifenilos Policlorados/química , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/sangre , Dibenzodioxinas Policloradas/química , Factores de TiempoRESUMEN
We conducted congener-specific analysis of non-dioxin-like polychlorinated biphenyls (non-dioxin-like PCBs) in blood collected in February 2004 from 127 elderly residents living in Nakagawa Town, Fukuoka Prefecture, Japan. The present study is one of the few studies in which 56 non-dioxin-like PCBs congeners were measured in human blood. Of the 127 elderly residents, 51 were men (mean: 68.1 years) and 76 were women (mean: 68.1 years). Among 197 non-dioxin-like PCB congeners, 56 were identified in the blood of elderly residents. The arithmetic mean total concentrations of 56 non-dioxin-like PCBs congeners in the blood of elderly men and women in Nakagawa Town were 419 (median: 378) and 363 (median: 323)ngg(-1)lipid, respectively, and the concentrations were in the range of 172-1102 and 119-1226ngg(-1)lipid, respectively, indicating that the total concentrations in elderly men are significantly higher than those in elderly women. The contamination of non-dioxin-like PCBs in the blood of elderly men and women in Fukuoka Prefecture was found to have decreased compared to past levels. The ratios of hexachlorinated biphenyls (hexaCBs) to the total concentrations of 56 non-dioxin-like PCBs congeners in the blood of elderly men and women were 44.6% and 45.6%, respectively, which was particularly high compared with those of other congeners. 2,2',4,4',5,5'-HexaCB (#153) among hexaCBs congeners, the most abundant congener in the blood of elderly men and women, contributed approximately 23.0% and 23.5% to the total concentrations of 56 non-dioxin-like PCBs congeners, respectively. Furthermore, 2,2',3,4,4',5'-hexaCB (#138), 2,3,3',4',5,6-hexaCB (#163)/2,3,3',4',5',6-hexaCB (#164), 2,2',3,4,4',5,5'-heptaCB (#180), and 2,2',3,4,4',5,6'-heptaCB (#182)/2,2',3,4',5,5',6-heptaCB (#187) also showed high ratios to the total concentrations of 56 non-dioxin-like PCBs congeners detected in the blood of elderly men and women. A statistical examination of the relationship between the total concentrations of 56 non-dioxin-like PCBs congeners in blood and the age of elderly residents who were over 60 years indicated statistically significant correlations between the total concentrations of these PCBs congeners and the age of elderly women. However, similar correlations were not observed in elderly men. The results of the present study have indicated the current levels of non-dioxin-like PCBs in the blood of elderly men and women in Fukuoka Prefecture, Japan and can be used as baseline data for those over age 60.
Asunto(s)
Contaminantes Ambientales/sangre , Contaminantes Ambientales/química , Bifenilos Policlorados/sangre , Bifenilos Policlorados/química , Anciano , Femenino , Humanos , Japón , Lípidos/sangre , MasculinoRESUMEN
We conducted a congener-specific analysis of non-dioxin-like polychlorinated biphenyls (non-dioxin-like PCBs) in blood collected between July 2002 and July 2004 from 195 pregnant women living in Sapporo City of Hokkaido Prefecture, Japan. The present study is one of the few studies in which full congener concentrations of non-dioxin-like PCBs have been measured in the blood of pregnant women. Of the 195 pregnant women, 101 were primipara (mean: 28.8 years, median: 28.0 years) and 94 were multipara (mean: 32.3 years, median: 33.0 years). Among the 197 non-dioxin-like PCB congeners, 58 congeners were identified in the blood of pregnant women. The arithmetic mean total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers in Sapporo City were 42.2-329.3 (mean: 114.5, median: 98.6) and 31.5-258.0 (mean: 100.3, median: 91.4)ngg(-1)lipid, respectively. The results show that the contamination of non-dioxin-like PCBs in the blood of women has decreased compared to past levels in other domestic areas, in which the subject age was similar to that in this study. The results of the present study indicate that current levels of non-dioxin-like PCBs in the blood of Japanese women and can be used as baseline data for future temporal trends. The sums of the ratios of the concentrations of hexaCBs and heptaCBs to the total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers were 78.5% and 77.7%, respectively. The hexaCBs ratios in the blood of primiparous and multiparous mothers were 45.4% and 44.7%, respectively. HexaCB-153 among hexaCBs congeners, the most abundant congener in the blood of primiparous and multiparous mothers, contributed approximately 22.0% and 21.8% to the total concentrations of 58 non-dioxin-like PCBs congeners that were measured in the blood, respectively. Among the non-dioxin-like PCB congeners measured in the present study, hexaCB-138, heptaCB-170, heptaCB-180, and heptaCB-182/heptaCB-187 also showed high ratios to total concentrations of 58 non-dioxin-like PCB congeners detected in the blood of primiparous and multiparous mothers. With regard to the relationship between the total concentrations of 58 non-dioxin-like PCB congeners in maternal blood and the number of deliveries or the age of primiparous and multifarious mothers, the total levels of these PCB congeners tended to decreases with increases in the number of deliveries and significantly increased with increasing maternal age in both groups. Furthermore, significant correlations were observed between the total concentrations of these PCB congeners in blood and the age of primiparae and multiparae. The concentrations of hexaCB-153 in the blood of primiparous and multiparous mothers showed a close correlation to the total concentrations of these PCBs, suggesting that hexaCB-153 could be an indicator of total concentrations of non-dioxin-like PCB congeners in the blood of pregnant women.
Asunto(s)
Contaminantes Ambientales/sangre , Contaminantes Ambientales/química , Bifenilos Policlorados/sangre , Bifenilos Policlorados/química , Adolescente , Adulto , Distribución por Edad , Monitoreo del Ambiente , Femenino , Humanos , Japón , Persona de Mediana Edad , Paridad , EmbarazoRESUMEN
We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs), and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) in paired samples of blood and breast milk collected from 60 mothers in Sapporo City, Hokkaido Prefecture, Japan. The present study is one of the few studies in which PCDDs, PCDFs, and dioxin-like PCBs have been measured in blood and breast milk collected from 60 same mothers. Of these 60 mothers, 30 were primipara (mean: 30.1 years, median: 28.0 years) and 30 were multipara (mean: 32.2 years, median: 32.5 years). The arithmetic mean TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of the primiparous mothers were 9.0, 3.3, 5.7, and 0.4 pg TEQ g(-1) lipid, respectively, and 5.2, 2.2, 4.5, and 0.4 pg TEQ g(-1) lipid, respectively, with the total TEQ concentrations of these dioxin-like compounds being 9.3-42.9 (mean: 18.4, median: 17.3) and 7.0-41.1 (mean: 12.3, median: 11.4) pg TEQ g(-1) lipid, respectively. In the case of multiparous mothers, the arithmetic mean TEQ concentrations of these dioxin-like compounds in blood and breast milk were 7.1, 2.7, 5.3, and 0.4 pg TEQ g(-1) lipid, respectively, and 3.9, 1.7, 3.8, and 0.4 pg TEQ g(-1) lipid, respectively, with the total TEQ concentrations being 3.4-28.1 (mean: 15.5, median: 13.9) and 2.7-20.0 (mean: 9.8, median: 9.2)pg TEQ g(-1) lipid, respectively. The total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk of primiparous mothers in Sapporo City appeared to be generally lower than those recently surveyed throughout the greater area of Japan. Significant correlations were observed between age and the total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of primiparae and multiparae, and significant correlations were also observed between age and the total TEQ concentrations of these dioxin-like compounds in the breast milk of primiparae and multiparae. The total TEQ concentrations of PCDDs, PCDFs, and dioxin-like PCBs in the blood of primiparous mothers showed a close correlation to those in their breast milk and also showed good correlations between the total TEQ concentrations of these dioxin-like compounds in the blood of multiparous mothers and those in their breast milk. The result of a comparison of the arithmetic mean concentrations of each congener of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in blood and breast milk indicated that the transfer of octachlorodibenzo-p-dioxin (OCDD) from the blood to the breast milk was lower than those of other congeners. In contrast, among mono-ortho PCBs congeners, the arithmetic mean concentrations of 2,3',4,4',5-pentachlorobiphenyl (PentaCB) (#118) and 2,3,3',4,4'-PentaCB (#105) in the breast milk were slightly higher than those in the blood, which suggested that breast-fed infants may be at higher risk from mono-ortho PCBs.