Mortality of short-term workers in two international cohorts.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

Exposure to styrene and mortality from nervous system diseases and mental disorders.

Chronic low-dose exposure to solvents has been associated in epidemiologic studies with chronic neurotoxicity, but the evidence is not consistent. Styrene causes acute disturbances in the central and peripheral nervous systems. To determine if exposure to styrene may contribute to chronic diseases of the central nervous system, the authors examined mortality from nervous system diseases, mental disorders, and suicide in relation to styrene exposure in an international historical cohort study. The cohort involved 35,443 workers employed during 1945-1991 in the reinforced plastics industry, where high exposures to styrene occur. Indicators of exposure were reconstructed through job histories and environmental and biologic monitoring data. Poisson regression was used for internal comparisons. Mortality from diseases of the central nervous system (27 deaths) increased with time since first exposure, duration of exposure, average level of exposure, and cumulative exposure to styrene. A quadratic model described best the dose-response shape for cumulative exposure and duration of exposure with the highest risks at around 300 ppm-years and 5 years, respectively, and a subsequent decrease in risk in the highest exposure categories. Mortality from epilepsy increased monotonically with all styrene exposure indicators, while associations for degenerative diseases of the central nervous system were generally weaker. Mortality from mental disorders and suicide decreased with increasing duration of exposure and cumulative exposure, while there was no trend with time since first exposure and average exposure to styrene. These findings suggest that, in addition to the known acute effects, exposure to styrene may contribute to chronic diseases of the central nervous system.

Exposure to styrene and mortality from nonmalignant respiratory diseases.

A cohort of 34,560 men and 6128 women employed in 660 European factories manufacturing reinforced plastic products, followed up originally to assess the risk of cancer, was used to assess the risk of non-malignant respiratory diseases associated with exposure to styrene. Mortality from pneumonia was associated with intensity of exposure to styrene, but this may have been due to chance. Mortality from bronchitis, emphysema, and asthma was not associated with styrene exposure.

Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system.

OBJECTIVES: A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. METHODS: The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. RESULTS: Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. CONCLUSIONS: In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.

Parietaria judaica-specific T-cell clones from atopic patients: heterogeneity in restriction, V beta usage, and cytokine profile.

The pollen of Parietaria spp. is one of the most clinically relevant sources of allergens in the Mediterranean area. CD4+ T-lymphocyte clones specific for Parietaria allergens were isolated from peripheral blood of atopic donors, and their phenotype, HLA restriction, V beta usage, and cytokine profile were determined. All the T-cell clones expressed the alpha/beta T-cell receptor and were induced to express CD40 ligand after activation with phorbol-myristate-acetate plus ionomycin. When the proliferative response to three chromatographic fractions of the extract was analyzed, distinct reactivity patterns were found. Interestingly, most of the clones responded to the fraction that was the most enriched for the major allergen Par j 1. The clones were either HLA-DR- or HLA-DQ-restricted and did not show any preferential usage of T-cell receptor V beta segments. Five of the 17 clones tested produced only IL-4 and no interferon-gamma, thus displaying a TH2 phenotype. The other clones displayed a TH0 phenotype in that they produced both IL-4 and interferon-gamma. These results show that in atopic patients T-cell response against Parietaria judaica allergen involves different T-cell subsets in terms of restriction, V beta usage, and cytokine profile.

Hepatitis autoinmune: 8 años de experiencia / Autoimmune hepatitis

Apresenta la experiencia de 8 años en el diagnóstico yseguimiento de 90 pacientes con hepatitis autoinmune. Las edades estaban comprendidas entre 21 meses y 14 años, perteneciendo 69 al sexo femenino y 21 al masculino. El comienzo de la enfermedad fue en la mayoría de los casos semejante a una hepatitis aguda, evolucionando 2 de ellos a una forma fulminante. Desde el punto de vista humoral, presentaban hipergamaglobulinemia, predominio del anticuerpo SMA positivo (88 pacientes). El tratamiento instituido en la mayoría de los pacientes fue la asociación de prednisona y azatioprina, lográndose el control de la enfermedad en el 62 por ciento de los casos. Un grupo de 31 pacientes, con manifestaciones de cirrosis avanzada (29 casos) o fallo hepático fulminante (2 casos), no se beneficiaron con el mencionado tratamiento, falleciendo 18 niños (20 por ciento), 11 recibieron un trasplante hepático y 2 se encuentran en lista de espera. Se destaca la necesidad del diagnóstico y tratamiento precoces de esta enfermedad evolutiva y fatal librada a su evolución espontánea

Hepatitis autoinmune: 8 años de experiencia / Autoimmune hepatitis

Apresenta la experiencia de 8 años en el diagnóstico yseguimiento de 90 pacientes con hepatitis autoinmune. Las edades estaban comprendidas entre 21 meses y 14 años, perteneciendo 69 al sexo femenino y 21 al masculino. El comienzo de la enfermedad fue en la mayoría de los casos semejante a una hepatitis aguda, evolucionando 2 de ellos a una forma fulminante. Desde el punto de vista humoral, presentaban hipergamaglobulinemia, predominio del anticuerpo SMA positivo (88 pacientes). El tratamiento instituido en la mayoría de los pacientes fue la asociación de prednisona y azatioprina, lográndose el control de la enfermedad en el 62 por ciento de los casos. Un grupo de 31 pacientes, con manifestaciones de cirrosis avanzada (29 casos) o fallo hepático fulminante (2 casos), no se beneficiaron con el mencionado tratamiento, falleciendo 18 niños (20 por ciento), 11 recibieron un trasplante hepático y 2 se encuentran en lista de espera. Se destaca la necesidad del diagnóstico y tratamiento precoces de esta enfermedad evolutiva y fatal librada a su evolución espontánea (AU)

Use of monoclonal antibodies in the standardization of Parietaria judaica allergenic extracts.

Two monoclonal antibodies (MoAb) specific for Parietaria judaica allergenic components were selected on the basis of their capability to recognize either the Parietaria judaica major allergen (MoAb 1A6/1D1) or several other allergenic components (MoAb 1A4/2F8) except the major allergen. These two antibodies, either individually or combined, were used to develop an ELISA-inhibition system using a reference Parietaria judaica extract (in-house Reference preparation, IHR). The assays performed with these reagents were firstly standardized by testing the IHR several times. A good reproducibility, evaluated both at the level of 50% inhibition values, and in terms of analysis of the variance of the slopes of the regression curves, was obtained. Subsequently, the potency of several Parietaria judaica extracts, either obtained by manufacturing companies or produced in other laboratories, was evaluated by these tests. Data obtained by interpolation with the IHR values and expressed in terms of arbitrary units (AU) were compared with those obtained by classical human IgE inhibition, performed with sera from allergic patients. Results indicate that the monoclonal antibodies produced in our laboratory can be successfully employed, either individually or combined, in the standardization of allergenic preparations in addition to, and possibly replacing, the classical IgE-based standardization procedures which require human specimens often available in limited amounts only.

[Air pollution and health risk communication]. / L'inquinamento atmosferico e la comunicazione del rischio per la salute.

The risk communication processes concerning atmospheric pollution and health effects in Modena, Reggio Emilia and Bologna, are described from the public health service point of view. The description includes the chronological developments, the principal events which influenced, or have been influenced by these risk communication processes, their most significant and critical aspects. Finally the air quality evaluation and its impact on risk communication is discussed.

[Goal-oriented projects of the Emilia Romagna region]. / I progetti finalizzati della Regione Emilia Romagna.

The Region of Emilia Romagna, on the basis of a 1983 specific regional law, funded two triennal plans of applied health researches. The fundamental criteria and the characteristics of these two plans are described. A particular attention is devoted to the projects concerning environmental and occupational health. The role of the local occupational health services in performing research activities and in using the results of the research projects are also described.

Cancer mortality in a historical cohort study of workers exposed to styrene.

OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

Constitutive and inducible profile of glutathione S-transferase subunits in biliary epithelial cells and hepatocytes isolated from rat liver.

The constitutive and inducible cytosolic glutathione S-transferase (EC 2.5.1.18) subunit compositions of parenchymal cells (hepatocytes) and biliary epithelial cells (BEC) from rat liver have been quantitatively analysed using reverse-phase h.p.l.c. Hepatocytes, analysed in the absence of non-parenchymal cells, expressed constitutively the following subunits, in order of their concentration: 3, 4, 2, 1a, 1b, 8, 6 and 10. BEC express constitutively only four of the GST subunits expressed by hepatocytes and these are, in order of their concentration: subunits 2, 7, 4 and 3. Notable differences from hepatocytes are that BEC completely lack the Alpha-class subunits 1a and 1b that are major subunits in hepatocytes, Mu-class subunits make up a very low proportion of the total, and the Pi-class subunit 7 is a major subunit in BEC, whereas it is essentially absent from hepatocytes. For the first time, the effects of the inducing agents phenobarbitone (PB), beta-naphthoflavone (beta-NF) and ethoxyquin (EQ) have been characterized in a comprehensive and quantitative manner in both cell types. PB, beta-NF and EQ increased total GST protein in hepatocytes by approx. 2-fold, 3-fold and 4-fold respectively. Subunits significantly induced in hepatocytes were (in order of fold-induction): by PB, 1b > 8 > 3 > 2 > 4; by beta-NF, 1b > 8 > 2 > 3 > 4; and by EQ, 7 > 1b > 10 > 8 > 3 > 2 > 1a > 4. In BEC, neither PB nor beta-NF had significant effects on the total amount of GST protein, although PB did significantly induce subunit 3 at the expense of other subunits. EQ increased total GST protein nearly 5-fold in BEC, subunits 7 and 3 being induced dramatically above constitutive levels.

Glutathione-S-transferase, alcohol dehydrogenase and aldehyde reductase activities during diethylnitrosamine-carcinogenesis in rat liver.

Several enzymes metabolize the toxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. During carcinogenesis induced by diethylnitrosamine in rat liver, an increase in aldehyde dehydrogenase, in comparison with normal liver, has already been shown. This paper demonstrates that, although to a lesser extent than aldehyde dehydrogenase, aldehyde reductase and glutathione-S-transferase also increase during carcinogenesis. Of the latter two enzymes, aldehyde reductase increases more markedly in a progressive fashion during the months of development of nodules and hepatoma. The increase of enzymes able to metabolize 4-hydroxynonenal, as well as other aldehydes, is certainly important in protecting tumour cells against cytotoxic effect of aldehydes.

Biological monitoring of styrene in the reinforced plastics industry in Emilia Romagna, Italy.

Biological monitoring of styrene exposure among workers in the reinforced plastics industry is widely implemented in the region of Emilia Romagna, Italy. More than 18,000 urine samples measurements of the main metabolites of styrene, mandelic (MA) and phenylglyoxylic acid, were retrieved for the period 1978-1990, and 4689 values of MA in postshift urine samples were analyzed for various variables thought to influence styrene exposure. The job performed was found to be the most important predictor of styrene exposure. Hand laminators had the highest exposure (mean MA 682 mg/g creatinine); spray laminators showed lower values (404 mg/g), while levels in semiautomatic process operators (243 mg/g) were only slightly higher than in nonprocess workers (186 mg/g). The use of ventilation resulted in lower exposure, but differences in average values were not particularly wide. Exposure decreased weakly during the study period in all work categories, but the percentage of measurements exceeding the current biological limit value (900 mg/g creatinine, 1300 mg/l corrected for density) is still very high (20% of measurements among hand laminators in 1990). These results indicate that the control measures implemented are only partially effective for the prevention of styrene exposure.

Cancer mortality in an international cohort of workers exposed to styrene.

Increased risks for leukaemia and lymphoma have been suggested in studies of workers exposed to styrene in the rubber and plastics industry. A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden and the United Kingdom involving 40,683 workers employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories, environmental and biological monitoring data and production records of the plants in the study. Cause-specific national death rates were used as the reference. Among exposed workers, no excess was observed for mortality from all causes (2195 deaths, standardized mortality ratio [SMR], 95; 95% confidence interval [CI], 91-99), from all neoplasms, from lung cancer or from other major epithelial cancers. Mortality from neoplasms of the lymphatic and haematopoietic tissues was not elevated (50 deaths; SMR, 96; CI, 71-126) and was not consistently associated with length of exposure. The rate of mortality from leukaemias and lymphomas increased with time since first exposure. Among subjects who had been exposed for more than one year, a two-fold risk was observed 20 years after first exposure (eight deaths; SMR, 197; CI, 85-387). These results are inadequate to exclude the possibility that styrene causes leukaemia and lymphoma.

Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis.

Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis.

Lipid peroxidation in rat AH-130 hepatoma cells enriched in vitro with arachidonic acid.

Tumor cells generally display low lipid peroxidation. A low content of polyunsaturated fatty acids in membrane phospholipids is a possible cause of their decreased susceptibility to lipid peroxidation. To investigate the importance of substrate availability in eliciting lipid peroxidation and to study cell viability in conditions of stimulated lipid peroxidation, AH-130 hepatoma cells were enriched with arachidonic acid. The enriched hepatoma cells showed increased mortality correlated with the increased incorporation of arachidonic acid in membrane phospholipids. When 0.5 mM arachidonic acid was added to hepatoma cells, this fatty acid reached a percentage content similar to that found in hepatocytes. Hepatoma cells enriched with this concentration were further incubated to determine their susceptibility to lipid peroxidation; mortality increased in parallel with increased thiobarbituric acid-reactive substance production. The highest mortality was in hepatoma cells treated with ascorbate/FeSO4. Mortality in normal cells was low, although they had a high production of thiobarbituric acid-reactive substances. The high capability of normal cells to metabolize the products of lipid peroxidation might explain the different viabilities of normal cells and hepatoma cells. It may therefore be possible to modify the composition of fatty acids of hepatoma cells in order to sensitize them to the toxic effect of prooxidant agents.

Comparative subcellular distribution of benzaldehyde and acetaldehyde dehydrogenase activities in two hepatoma cell lines and in normal hepatocytes.

The NAD- and NADP-dependent aldehyde dehydrogenase (ALDH) activities were evaluated in two rat hepatoma cell lines, namely the well-differentiated MH1C1 line and the less differentiated HTC line. Each activity was determined in parallel in isolated rat hepatocytes, for comparison. The aliphatic aldehyde acetaldehyde (ACA) and the aromatic aldehyde benzaldehyde (BA) were used as substrates. With the first substrate the ALDH activities found in the crude cytoplasmic extracts were lower in hepatoma cells than in normal hepatocytes, especially when measured with NADP as coenzyme (ACA/NADP). Otherwise, with benzaldehyde as substrate the NAD-dependent enzyme activity (BA/NAD) was increased about 9-fold in HTC cells over hepatocytes and decreased in MH1C1 cells, while the NADP-dependent (BA/NADP) activity was increased 38- and 2.5-fold in HTC and MH1C1 cell lines, respectively. Studies on the subcellular distribution of these enzyme activities showed that the activity measured with acetaldehyde and NAD (ACA/NAD) was almost equally distributed between the cytosol and the subcellular particles in the three cell populations, but the ACA/NADP activity was shifted towards the cytosolic compartment in hepatomas, especially in HTC cells. The BA/NAD and BA/NADP ALDH activities found in the organelles of hepatoma cells were markedly reduced in comparison with hepatocytes, in favour of the cytosol. The most striking difference between the normal and the transformed cells was the 94-fold increase over hepatocytes of the BA/NADP activity, found in the cytosolic fractions of HTC cells. MH1C1 cells showed a less pronounced (7.5-fold) enhancement of this tumour-associated specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)