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H. C. Hopf - One of the best experts on this subject based on the ideXlab platform.
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Cranial nerve function in workers exposed to polychlorinated dioxins and furans.
Acta neurologica Scandinavica, 2002Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:OBJECTIVE: To look for possible effects of polychlorinated dioxins and furans (PCDD/F) on cranial nerve function. MATERIAL AND METHODS: Clinical and neurophysiological examinations [visual and brainstem auditory evoked potentials (VEP and BAEP), blink reflex] in 121 PCDD/F exposed workers of one pesticide producing plant. RESULTS: BAEP abnormalities were more frequent in workers with Chloracne (6 of 33 workers, 18.2%) than in those without Chloracne (7 of 84, 8.3%), but this was not statistically significant (chi2: 2.33). VEP abnormalities were seen in one worker with and two without Chloracne. Clinically visual functions were normal except in one worker, who was amaurotic since birth. Blink reflex abnormalities without corresponding clinical findings were observed in two patients without Chloracne. CONCLUSION: Severe exposure to PCDD/F is not followed by clinical signs of cranial nerve dysfunction but may create an increased risk for abnormal BAEP findings, which were more than twice as common in workers with Chloracne. Although this difference did not reach statistical significance, it cannot exclude a toxic effect of PCDD/F, as statistical significance is difficult to achieve with such small numbers of workers. In none of the workers, BAEP abnormalities were accompanied by clinical signs of hearing dysfunction.
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increased risk of sensory neuropathy in workers with Chloracne after exposure to 2 3 7 8 polychlorinated dioxins and furans
Acta Neurologica Scandinavica, 1999Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:Objective - The existence of a peripheral neuropathy after exposure to polychlorinated dioxins (PCDD) is still discussed, as studies concerning dioxin effects on the peripheral nervous system are rare and contradictory. Material and methods - Clinical and neurophysiological examinations (motor conduction velocity of the peroneal nerve, sensory conduction velocities of the sural and ulnar nerves) were made in 156 dioxin exposed workers (42 with, 114 without cloracne) from one pesticide producing plant. Because of known risk factors for peripheral neuropathy, 7 workers with and 28 without cloracne were excluded from further analysis. Results - Workers with Chloracne had a significantly higher exposure against PCDD as documented by back calculated lipid levels. They complained significantly more often of sexual impotence (28.6% compared to 5.8% of workers without Chloracne, P<0.001), had significantly more frequent clinical signs of a sensory neuropathy (=abnormal sensory findings plus deep tendon reflex abnormalities) restricted to the legs (17.1% compared to 1.2%, P<0.001), had significantly more frequent ≥2 neurophysiologic abnormalities (34.3% compared to 14.0%, P<0.025), and had significantly lower mean amplitudes of the motor compound muscle potential of the peroneal nerve. Conclusion - PCDD has a mild toxic effect on the peripheral nervous system manifesting as mild sensory neuropathy of the legs in a minority of the most severely exposed persons.
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Increased risk of sensory neuropathy in workers with Chloracne after exposure to 2,3,7,8-polychlorinated dioxins and furans.
Acta neurologica Scandinavica, 1999Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:Objective - The existence of a peripheral neuropathy after exposure to polychlorinated dioxins (PCDD) is still discussed, as studies concerning dioxin effects on the peripheral nervous system are rare and contradictory. Material and methods - Clinical and neurophysiological examinations (motor conduction velocity of the peroneal nerve, sensory conduction velocities of the sural and ulnar nerves) were made in 156 dioxin exposed workers (42 with, 114 without cloracne) from one pesticide producing plant. Because of known risk factors for peripheral neuropathy, 7 workers with and 28 without cloracne were excluded from further analysis. Results - Workers with Chloracne had a significantly higher exposure against PCDD as documented by back calculated lipid levels. They complained significantly more often of sexual impotence (28.6% compared to 5.8% of workers without Chloracne, P
Andrea Baccarelli - One of the best experts on this subject based on the ideXlab platform.
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Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects.
Toxicology, 2006Co-Authors: Cliona M. Mchale, Andrea Baccarelli, Angela C. Pesatori, Luoping Zhang, Alan Hubbard, Xin Zhao, Martyn T. Smith, Maria Teresa LandiAbstract:Abstract Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (Chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7 ppt, respectively); the second compared subjects who developed Chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on Chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between Chloracne case–control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted.
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Health status and plasma dioxin levels in Chloracne cases 20 years after the Seveso, Italy accident
The British journal of dermatology, 2005Co-Authors: Andrea Baccarelli, Angela C. Pesatori, D. Consonni, P. Mocarelli, Donald G. Patterson, N. E. Caporaso, Pier Alberto Bertazzi, M T LandiAbstract:Summary Background The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of Chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. Objectives Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of Chloracne cases; (b) TCDD-Chloracne exposure–response relationship; and (c) factors modifying TCDD toxicity. Methods From 1993 to 1998, we recruited 101 Chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography/mass spectrometry. Results Plasma TCDD was still elevated (> 10 ppt) in 78 (26·6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of Chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with Chloracne [odds ratio (OR) = 3·7, 95% confidence interval (CI) 1·6–8·8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7·4, 95% CI 1·8–30·3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of Chloracne (OR = 9·2, 95% CI 2·6–32·5). Conclusions Dioxin toxicity in Chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results.
Frank Thömke - One of the best experts on this subject based on the ideXlab platform.
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Cranial nerve function in workers exposed to polychlorinated dioxins and furans.
Acta neurologica Scandinavica, 2002Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:OBJECTIVE: To look for possible effects of polychlorinated dioxins and furans (PCDD/F) on cranial nerve function. MATERIAL AND METHODS: Clinical and neurophysiological examinations [visual and brainstem auditory evoked potentials (VEP and BAEP), blink reflex] in 121 PCDD/F exposed workers of one pesticide producing plant. RESULTS: BAEP abnormalities were more frequent in workers with Chloracne (6 of 33 workers, 18.2%) than in those without Chloracne (7 of 84, 8.3%), but this was not statistically significant (chi2: 2.33). VEP abnormalities were seen in one worker with and two without Chloracne. Clinically visual functions were normal except in one worker, who was amaurotic since birth. Blink reflex abnormalities without corresponding clinical findings were observed in two patients without Chloracne. CONCLUSION: Severe exposure to PCDD/F is not followed by clinical signs of cranial nerve dysfunction but may create an increased risk for abnormal BAEP findings, which were more than twice as common in workers with Chloracne. Although this difference did not reach statistical significance, it cannot exclude a toxic effect of PCDD/F, as statistical significance is difficult to achieve with such small numbers of workers. In none of the workers, BAEP abnormalities were accompanied by clinical signs of hearing dysfunction.
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increased risk of sensory neuropathy in workers with Chloracne after exposure to 2 3 7 8 polychlorinated dioxins and furans
Acta Neurologica Scandinavica, 1999Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:Objective - The existence of a peripheral neuropathy after exposure to polychlorinated dioxins (PCDD) is still discussed, as studies concerning dioxin effects on the peripheral nervous system are rare and contradictory. Material and methods - Clinical and neurophysiological examinations (motor conduction velocity of the peroneal nerve, sensory conduction velocities of the sural and ulnar nerves) were made in 156 dioxin exposed workers (42 with, 114 without cloracne) from one pesticide producing plant. Because of known risk factors for peripheral neuropathy, 7 workers with and 28 without cloracne were excluded from further analysis. Results - Workers with Chloracne had a significantly higher exposure against PCDD as documented by back calculated lipid levels. They complained significantly more often of sexual impotence (28.6% compared to 5.8% of workers without Chloracne, P<0.001), had significantly more frequent clinical signs of a sensory neuropathy (=abnormal sensory findings plus deep tendon reflex abnormalities) restricted to the legs (17.1% compared to 1.2%, P<0.001), had significantly more frequent ≥2 neurophysiologic abnormalities (34.3% compared to 14.0%, P<0.025), and had significantly lower mean amplitudes of the motor compound muscle potential of the peroneal nerve. Conclusion - PCDD has a mild toxic effect on the peripheral nervous system manifesting as mild sensory neuropathy of the legs in a minority of the most severely exposed persons.
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Increased risk of sensory neuropathy in workers with Chloracne after exposure to 2,3,7,8-polychlorinated dioxins and furans.
Acta neurologica Scandinavica, 1999Co-Authors: Frank Thömke, D. Jung, R. Besser, R. Röder, J. Konietzko, H. C. HopfAbstract:Objective - The existence of a peripheral neuropathy after exposure to polychlorinated dioxins (PCDD) is still discussed, as studies concerning dioxin effects on the peripheral nervous system are rare and contradictory. Material and methods - Clinical and neurophysiological examinations (motor conduction velocity of the peroneal nerve, sensory conduction velocities of the sural and ulnar nerves) were made in 156 dioxin exposed workers (42 with, 114 without cloracne) from one pesticide producing plant. Because of known risk factors for peripheral neuropathy, 7 workers with and 28 without cloracne were excluded from further analysis. Results - Workers with Chloracne had a significantly higher exposure against PCDD as documented by back calculated lipid levels. They complained significantly more often of sexual impotence (28.6% compared to 5.8% of workers without Chloracne, P
Nai-jun Tang - One of the best experts on this subject based on the ideXlab platform.
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Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of Chloracne patients exposed to dioxins.
Toxicology letters, 2011Co-Authors: Jing Liu, Chun-mei Zhang, Li Dong, Wei Han, Pieter-jan Coenraads, Xi Chen, Nai-jun TangAbstract:Objective: Chloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced Chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of Chloracne related to dioxin exposures. Methods: Epidermal tissues of twelve Chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively. Results: p-EGFR and p-MAPK were found in all Chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all Chloracne lesions, but none in controls (P = 0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the Chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum. Conclusions: The results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of Chloracne related to dioxin exposures. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin-exposed humans with Chloracne.
Toxicology letters, 2008Co-Authors: Nai-jun Tang, Chun-mei Zhang, Li Dong, Li-jun Zhao, Jing Liu, Pieter-jan Coenraads, Xi Chen, Wen-guo WeiAbstract:Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause Chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated Chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through Chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue of Chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of Chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of Chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to Chloracne. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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Role of mitogen-activated protein kinase pathway in Chloracne
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational di, 2008Co-Authors: Chun-mei Zhang, Nai-jun Tang, Li Dong, Li-jun Zhao, Wen-guo Wei, Wan-qi Zhang, Peng Zhang, Wei HanAbstract:OBJECTIVE To investigate the role of mitogen-activated protein kinase (MAPK) signal transduction pathway in Chloracne. METHODS Immunohistochemical technique was used to detect the expression of phosphorylated epidermal growth factor receptor (p-EGFR) and p-MAPK proteins in the epithelium of Chloracne group and control group. RESULTS p-EGFR and p-MAPK was found in all Chloracne tissues, whereas no expression of p-EGFR and p-MAPK protein was found in control group. In the skin of Chloracne patients, p-EGFR was mainly distributed in the membrane and the cytoplasm, especially in the vicinity of membrane; major positive signal of p-MAPK was in core and serosity. CONCLUSION EGFR and MAPK phosphorylation is found in Chloracne tissues. MAPK signal transduction pathway is one important molecular mechanism of Chloracne.
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Blood lipid concentrations of dioxins and dibenzofurans causing Chloracne.
The British journal of dermatology, 1999Co-Authors: Pieter-jan Coenraads, K Olie, Nai-jun TangAbstract:Chloracne is caused by exposure to certain halogenated polycyclic hydrocarbons such as polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). In chronic exposure it is not known what level of intoxication, represented by the level in blood lipids, is sufficient to cause Chloracne. Blood levels of the congeners of PCDD/Fs were determined in four groups of humans. One group had clinically visible Chloracne due to exposure in a hexachlorobenzene workshop of a large chemical factory. A second group was exposed in the same workshop, but had no skin changes. There were two control groups: one non-exposed group of maintenance workers from the same chemical factory, and one group of healthy individuals living elsewhere. Blood levels were converted to toxicity equivalents of tetrachlorodibenzo-p-dioxin (TCDD). In the Chloracne group blood levels in toxicity equivalents (TEQs) ranged from 1168 to 22,308 pg/g blood lipid. In the exposed without Chloracne this ranged from 424 to 662 pg/g. It is concluded that the level to develop Chloracne is between 650 and 1200 pg/g TEQ. The contribution of TCDD was rather small, and the main causative congeners were the hexachlorinated dibenzodioxins and dibenzofurans (HxCDD/Fs); lipid-based blood levels in absolute amounts that may cause Chloracne are in the range of 2-3.5 ng/g HxCDD, and 2-5 ng/g HxCDF.
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Chloracne. Some recent issues.
Dermatologic clinics, 1994Co-Authors: Pieter-jan Coenraads, Abraham Brouwer, Kees Olie, Nai-jun TangAbstract:Chloracne is an acneiform skin eruption that is still the most sensitive indicator of systemic poisoning caused by chemicals belonging to the group of chlorinated polycyclic aromatic hydrocarbons. Generally these chemicals are known as dioxins, dibenzofuranes, and PCBs. The cause of Chloracne is probably interference of these chemicals with vitamin A metabolism in the skin, resulting in disturbances of the epithelial tissues of the pilosebaceous duct. A study of workers in a factory where Chloracne is endemic is described. The product manufactured, pentachlorophenol, a wood preservative, was found to be contaminated with dioxins (congeners of TCDD) and dibenzofuranes. Blood levels of these chemicals in affected workers are given, along with supporting evidence of disturbances in vitamin A (retinoid) metabolism as demonstrated in skin biopsies.
Angela C. Pesatori - One of the best experts on this subject based on the ideXlab platform.
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Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects.
Toxicology, 2006Co-Authors: Cliona M. Mchale, Andrea Baccarelli, Angela C. Pesatori, Luoping Zhang, Alan Hubbard, Xin Zhao, Martyn T. Smith, Maria Teresa LandiAbstract:Abstract Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (Chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7 ppt, respectively); the second compared subjects who developed Chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on Chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between Chloracne case–control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted.
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Health status and plasma dioxin levels in Chloracne cases 20 years after the Seveso, Italy accident
The British journal of dermatology, 2005Co-Authors: Andrea Baccarelli, Angela C. Pesatori, D. Consonni, P. Mocarelli, Donald G. Patterson, N. E. Caporaso, Pier Alberto Bertazzi, M T LandiAbstract:Summary Background The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of Chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. Objectives Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of Chloracne cases; (b) TCDD-Chloracne exposure–response relationship; and (c) factors modifying TCDD toxicity. Methods From 1993 to 1998, we recruited 101 Chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography/mass spectrometry. Results Plasma TCDD was still elevated (> 10 ppt) in 78 (26·6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of Chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with Chloracne [odds ratio (OR) = 3·7, 95% confidence interval (CI) 1·6–8·8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7·4, 95% CI 1·8–30·3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of Chloracne (OR = 9·2, 95% CI 2·6–32·5). Conclusions Dioxin toxicity in Chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results.