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Perchloroethylene exposure in 28 dry-cleaning establishments and in 25 homes occupied by dry cleaners in Modena, Italy, was investigated. Environmental air samples and alveolar air samples from dry cleaners (n = 60) and from their family members (n = 23) were collected. The degree of perchloroethylene on the dry-cleaning premises varied widely from establishment to establishment. Spot sampling ranged from 0.6 to 75 mg/m3, whereas sampling by personal passive dosimeters ranged from 2.6 to 221.5 mg/m3 (8-h time weighted average values). Perchloroethylene in alveolar air samples collected at the end of the work day correlated closely with the 8-h time weighted average values (r = .750, p = .001), and correlated also with alveolar air samples collected at home in the evening (r = .665, p = .001) and the following morning (r = .549, p < .001). Perchloroethylene levels inside the homes of dry cleaners appeared significantly higher than in 29 houses selected as controls (Mann Whitney U test, p < .001). Perchloroethylene in alveolar air samples collected at home suggests that nonoccupational exposure to perchloroethylene for family members of dry cleaners exists.

Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, and major changes in the concentration of liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator of the inflammatory response, together with IL-1 and tumor necrosis factor alpha (TNF-alpha). The purpose of this study was to unequivocally determine the role of IL-6 in these phenomena making use of IL-6-deficient mice that we have recently generated by gene targeting. We report here that in the absence of IL-6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection. The induction of acute phase proteins is dramatically reduced, mice do not lose body weight and only suffer from mild anorexia and hypoglycemia. In contrast, when systemic inflammation is elicited through the injection of bacterial lipopolysaccharide (LPS), these parameters are altered to the same extent both in wild-type and IL-6-deficient mice, demonstrating that under these conditions IL-6 function is dispensable. Moreover, we show that LPS-treated IL-6-deficient mice produce three times more TNF-alpha than wild-type controls, suggesting that increased TNF-alpha production might be one of the compensatory mechanisms through which a normal response to LPS is achieved in the absence of IL-6. We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis. Our results reinforce the idea that different patterns of cytokines are involved in systemic and localized tissue damage, and identify IL-6 as an essential mediator of the inflammatory response to localized inflammation.

The results of a study on Zn, Cu, Ca and Mg content in whole saliva and supernatant of young adults in relation to caries prevalence are reported. A total of 225 university students were selected for the study on the basis of voluntary participation. The salivary electrolytes showed a high intersubjective variability and females had significantly lower levels than males. In whole saliva, the trace elements were highly correlated, whereas the correlations were weaker in the supernatant. The ratio supernatant/whole saliva varied between subjects and according to the examined electrolytes. No association could be found between the measured trace elements and DMFT. When we analysed the relation with recent caries experience in the subgroup of subjects undergoing oral examinations for at least 1 year, we found evidence that the Zn/Cu molar ratios in whole saliva were significantly decreased in subjects with more than three decayed teeth compared with those with no caries (1.54 vs. 1.11, P < 0.05). No significant association was found when supernatant was analysed. We conclude that the electrolytes' levels in whole saliva might be more adequate than the levels in supernatant to evaluate the relationship with caries.

We have previously shown that chlorpromazine (CPZ) inhibits tumour necrosis factor (TNF) production and protects against endotoxic shock in mice. In this paper we investigated the effect of pretreatment with CPZ, 4 mg/kg i.p. 30 min before, compared with dexamethasone (DEX; 3 mg/kg) on the induction of other endotoxin (lipopolysaccharide; LPS)-induced cytokines in the serum of mice, i.e. interleukin-1 alpha (IL-1 alpha), IL-6 and IL-10, and TNF. We also studied the effect of CPZ on serum and spleen-associated TNF. Both DEX and CPZ inhibited TNF production, whereas induction of IL-1 and IL-6 was inhibited by DEX but not by CPZ. DEX did not affect IL-10, while CPZ potentiated its induction. CPZ also inhibited spleen-associated TNF induction in LPS-treated mice, suggesting an effect on the synthesis of TNF. CPZ inhibited TNF induction by Gram-positive bacteria (heat-killed Staphylococcus epidermidis) and by anti-CD3 monoclonal antibodies. Intraperitoneal administration of CPZ also inhibited the induction of brain-associated TNF induced by intra-cerebroventricular injection of LPS. Therefore, CPZ is a more specific inhibitor of TNF production than DEX; in particular, CPZ increased the induction of IL-10, which is a 'protective' cytokine known to inhibit LPS toxicity and TNF production. CPZ inhibited TNF production in vivo, irrespective of the TNF stimulus used to induce TNF. Finally, CPZ did not induce the 'rebound' effect of DEX that, when given 24 hr before LPS, potentiates TNF production, but it did inhibit TNF production after 24 hr.

Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24-48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.

A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cell is also important for interleukin-6 induction. All vaccines studied were very poor tumor necrosis factor inducers.

Cytokines play a pathogenetic role in a variety of infective and inflammatory diseases. In the present study, we had two objectives: (a) to define the kinetics of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI) in patients treated with early thrombolysis, and (b) to measure other cytokines, interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-alpha, but not IL-1 beta or IL-8, was present in plasma of 6 of 7 patients with severe AMI (Killip class 3 or 4). No TNF (< 50 pg/ml) was detected in a group of 11 patients with uncomplicated myocardial infarction (Killip class 1) or in control patients without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra) were also significantly increased in the group with severe AMI compared with those with uncomplicated AMI. Circulating TNF is increased only in AMI complicated by heart failure at hospital admission. This finding may have diagnostic and therapeutic relevance.

We investigated the pattern of down-regulation of cytokine production in endotoxin (lipopolysaccharide [LPS]) tolerance. A 4-day treatment with LPS (35 micrograms per mouse) was followed by a challenge on day 6 with one more injection of LPS. Circulating tumor necrosis factor (TNF) and interleukin-6 (IL-6) could not be induced (> 99% inhibition) by LPS in LPS-tolerant mice; colony-stimulating factor (CSF) was also down-regulated by more than 95%, whereas interferon (IFN) and IL-1 syntheses were only partially inhibited. To study the mechanism of cytokine down-regulation in tolerance, we attempted to reverse the tolerant state by pretreatment with phorbol 12-myristate 13-acetate (PMA) (4 micrograms per mouse) 10 min before the LPS challenge. PMA completely restored IL-6 production and partially that of CSF. PMA had no effect on IFN production and inhibited the induction of IL-1. TNF production was also not restored by PMA. To investigate the role of endogenously produced cytokines in the development of LPS tolerance, we administered IL-6, TNF, or IL-1 alpha, using the same treatment schedule as that for LPS. Whereas IL-6 had no effect, IL-1 alpha or TNF induced partial tolerance to LPS in terms of inhibition of LPS-stimulated TNF and IL-6 production. However, a full LPS-tolerant state could not be induced by administration of recombinant cytokines, suggesting the existence of additional mechanisms, such as a loss of LPS receptors or changes in release of soluble binding proteins.

Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and TNF, have been implicated in some ROI-mediated pathologies, including bleomycin toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no significant production of IL-8 protein was detected. However, PQ potentiated the production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide, LPS). This was paralleled by an increased production of chemotactic activity for neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8 mRNA by PQ was suppressed by IL-4 and by free radical scavengers (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed in the human pulmonary epithelial cell line A549 indicating that the effect of PQ was not specific for PBMC. These findings suggest that IL-8 might be involved in the pulmonary effects of PQ and that its production might be stimulated following an oxidative insult, and might clarify the pathogenetic mechanisms of adult respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.

We tested the effect of different inhibitors of cytochrome P450 on tumor necrosis factor (TNF) production. Metyrapone and SKF525A (100 and 50 mg/kg, ip, respectively) suppressed serum TNF induced by cotreatment with endotoxin (LPS), (2.5 micrograms/mouse). Inhibition was independent of endogenous corticosteroids since it was also observed in adrenalectomized mice. In vitro production of TNF by endotoxin-stimulated human monocytes was also inhibited by metyrapone and SKF525A. Since lipoxygenase (LO) inhibitors also block TNF production and metyrapone was reported to inhibit LO, we suggest that inhibition by metyrapone and SKF525A might be due to inhibition of either LO or a cytochrome P450 implicated in the oxidation of endogenous substrates involved in the inflammatory response.

We studied the effect of a 4-hr preexposure to LPS on the ability of human monocytes to respond to a subsequent stimulation with LPS in terms of cytokine production. LPS-preexposed monocytes did not produce TNF on LPS restimulation, but they retained the ability to produce IL-1 beta, IL-6, and IL-8. LPS-tolerant monocytes were still capable of producing TNF when restimulated with zymosan. Down-regulation of TNF by LPS tolerance was also evident at the mRNA level. To investigate the possible mechanisms underlying this phenomenon, we also studied the effect of LPS preexposure on membrane CD14, which was suggested to be an LPS receptor, and on intracellular cAMP, an inhibitor of TNF production. LPS induced a 50% decrease in CD14 expression. On the other hand, the increase in cAMP levels by LPS was not affected by preexposure to LPS. In conclusion, (a) TNF is more rapidly down-regulated than IL-1 beta, IL-6, and IL-8 during LPS tolerance in vitro; (b) early LPS tolerance is associated with decreased CD14, which might partially explain the decreased LPS response; and (c) a feedback mechanism controlling TNF synthesis, cAMP elevation, is not down-regulated in LPS tolerance.

Alveolar air samples were collected from 163 subjects at indoor swimming pools and from 77 nonexposed subjects. Chloroform was present in all samples collected from exposed subjects (median = 695.02 nmol/m3). It was found at very low levels in 53% of samples from nonexposed subjects. Alveolar air chloroform levels from people attending indoor swimming pools (mean value within each sampling session) were correlated with environmental air concentration (r = 0.907, p = .002). Analysis of variance showed that levels of chloroform in alveolar air depend on environmental air concentration, age, intensity of the sport activity, and kind of swimming. Chloroform levels in samples collected from competitive swimmers versus nonswimming visitors were different (F = 10.911, p = .001). Moreover, their pattern of swimming may affect chloroform concentration in alveolar air. The analysis of chloroform in alveolar air assesses indoor exposure in healthy subjects simply and at low cost.

Glucocorticoids are potent inhibitors of inflammation and endotoxic shock. This probably occurs through an inhibition of the synthesis of pro-inflammatory cytokines as well as of many of their toxic activities. Therefore, endogenous glucocorticoids (GC) might represent a major mechanism in the control of cytokine mediated pathologies. GC inhibit the synthesis of cytokines in various experimental models. Adrenalectomy or GC antagonists potentiate TNF, IL-1 and IL-6 production in LPS treated mice. GC inhibit the formation of arachidonic acid metabolites and the induction of NO synthase. They also inhibit various activities of cytokines including toxicity, haemodynamic shock and fever. Adrenalectomy sensitizes to the toxic effects of LPS, TNF and IL-1. On the other hand, GC potentiate the synthesis of several cytokine induced APP by the liver. Since many of these proteins have anti-toxic activities (antioxidant, antiprotease etc.) or bind cytokines, this might well represent a GC mediated protective feedback mechanism involving the liver. Not only do GC inhibit cytokines, but in vivo LPS and various cytokines (TNF, IL-1, IL-6) increase blood GC levels through a central mechanism involving the activation of the HPA. Thus, this neuroendocrine response to cytokines constitutes an important immunoregulatory feedback involving the brain.

The possible effects of moderate lead exposure on human growth and development are not well defined. This study was carried out in order to evaluate the relationship between somatic growth and lead exposure. 418 subjects (202 males and 216 females) aged 11-13 years in good health and living in an area of the northern region of Italy were submitted to the following determinations: blood lead levels (PbB), serum concentrations of gonadotropins (LH, FSH) and sex-steroid hormones (DHA-S, T, E2) and anthropometric measurements (stature and weight). The mean blood levels were 85.39 and 70.08 micrograms/1, respectively, for males and females. Significant and negative relationships were found between blood lead levels and stature in 13 years old males and 12 years old females (p = 0.009 and p = 0.006, respectively). Negative relationships between lead in blood and LH and FSH were found only in males with lead levels higher than 90 micrograms/1. Our findings seem to suggest that even for low lead exposure this metal may affect stature growth and gonadotropins levels.

We have measured the levels of zinc in serum (Zn-S) and in hair (Zn-H) in 391 adolescents, in good health, aged between 11 and 14 years. To evaluate the relationship between zinc status and sexual maturation we have analyzed, in the same subjects, the serum concentrations of the following hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone-sulphate (DHA-S), testosterone (T) and estradiol (E2). No significant relationship between zinc in the biological samples and the hormones measured in all subjects was observed; only in prepuberal females was a positive correlation found between Zn-S and E2. A significant relationship between Zn-S and LH was observed only for males with short stature or low weight (less than 25th percentile) (r = 0.359, p = 0.010; r = 0.47, p = 0.008, respectively). When prepuberal males with short stature were considered, a significant association between Zn-S and T appeared (r = 0.399, p = 0.006). In females with short stature (less than 25th percentile), partial correlation coefficients showed a significant association between FSH and zinc in hair (r = 0.435, p = 0.004), while in girls with low weight, FSH appeared positively related to zinc in hair (r = 0.470, p = 0.003) and negatively related to zinc in serum (r = -0.320, p = 0.050). Our results suggest that zinc plays an important role in the metabolism of hormones linked to sexual maturation.

This study evaluated swimmers and visitors who were exposed to chloroform (CHCl3) at three indoor swimming pools in Modena, Italy. Chloroform was measured in plasma samples of 127 subjects present at the pools and in 40 nonexposed subjects. The analyses were performed by head-space gas chromatography. Chloroform was present in all samples collected from the 127 subjects who attended the pools (median = 7.5 nmol/l; range = 0.8-25.1 nmol/l). Agonistic swimmers who trained for competitions showed a significantly higher mean value of plasma CHCl3 than nonagonistic swimmers and visitors. Plasma CHCl3 levels were significantly correlated with (a) CHCl3 concentrations in water and in environmental air, (b) the number of swimmers in the pools, and (c) the time spent swimming. Covariance analysis showed that plasma CHCl3 levels also depended on the intensity of the sport activity (total explained variance = 67.4%).

The Authors confirm the importance of fluoroprophylaxis in the prevention of Dental caries. They analyze the main methods of fluoroprophylaxis pointing out the systemic fluoroprophylaxis, effected by means of water fluoruration, as the best one for a valid prevention of dental caries on a large scale. In view of such a kind of fluoroprophylaxis in our country the Authors considered quite interesting to effect a research about the amount of fluoride in the waters of the district of Modena. The whole of results are reported.

Natural killer (NK) activities of fresh and IL-2-precultured peripheral blood mononuclear cells (PBMC) were investigated in 13 elderly subjects before and after thymopentin (TP-5) treatment and in 12 age-matched controls. The NK activity of fresh PBMC was found to be significantly higher in subjects given TP-5 at 50 mg s.c. three times per week for one month. Conversely, this type of treatment with TP-5 did not significantly modify the cytotoxic capacity of IL-2-precultured PBMC.

A case-control study was performed to assess whether cadmium is related to hypertension in a non-occupationally exposed population. 63 male subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 63 male normotensive controls individually matched for sex, age, body mass index, smoking habits and work activities. Cadmium in blood, zinc and copper in serum, the three elements in urine and hair, together with some biological parameters involved in pathogenesis of hypertension, were investigated. The mean Cd blood value in hypertensives (H) was 0.58 micrograms/L vs 0.44 micrograms/L in normotensives (N) (t = 2.03; p less than 0.05) with a greater difference in non-smokers (0.41 micrograms/L vs 0.25 micrograms/L) (t = 2.69, p less than 0.01). Furthermore, both systolic and diastolic blood pressure were significantly related to cadmium blood levels (r = 0.20 and 0.19 respectively, p less than 0.05). Smoking habit affected cadmium levels only in the blood, not in the other biological matrices examined. No significant difference of cadmium content in urine and hair was found between normotensives and hypertensives but Cd/Cu ratio in urine was significantly lowered in the second group.

The AA. have studied the weekly changes of haematic and urinary parameters of lead occupational exposure. For this aim, they have collected in 14 ceramic workers 3 blood samples for day and all urine samples for day and all urine samples from monday to friday. The PbB and FEP levels did not show significant variations during working week. The measurement of ALA in single urines shows that this parameter is characterized by remarkable fluctuations within the same day in all subjects examined. The correction of values by density gave negative results while the correction by creatinine decreases the daily fluctuations but only in some cases. The execution of test in urine of 24 hours seems to give the most reliable correlation with lead exposure levels because of its relative constancy during week.

Exposure to chloroform (CHCl3) in indoor swimming pool swimmers. CHCl3 presence has been evidenced many times in water and air of indoor pools as a consequence of water chlorination with sodium hypochlorite or other chlorinated disinfectants. In previous studies CHCl3 in environmental air appeared at a high concentration within one meter over the surface of the water and was correlated to the number of swimmers inside the pool. CHCl3 has also been evidenced in blood serum samples of people present at the swimming pool, at different levels depending on: the concentration in the environmental air, the intensity and the length of the sport activity and the number of swimmers in the pool. At the end of the swimming session CHCl3 concentration tends to lower quickly and usually is no longer detectable within half an hour. Other studies have evidenced CHCl3 in breath samples (alveolar air) of a volunteer subject who swam one hour every day in an indoor pool in Modena. The spirometric parameters of the same subject were evaluated in order to estimate his CHCl3 uptake during time spent at the swimming pool, both resting and swimming in different modes. In the present paper the A.A. report data about CHCl3 exposure, intake and uptake bin five agonistic swimmers (three males and two females), members of the same sport association, and regularly attending the same indoor swimming pool in Modena. The five subjects have been examined during four different sessions. Within every session the samples were collected in five different moments according to the following scheme: 1) Hygiene Institute: samples of blood, alveolar air, environmental air. 2) Swimming pool, after 1 hour sitting near the pool edge: samples of alveolar air, environmental air (within 1 m on the water surface). 3) Swimming pool, after 1 hour swimming: samples of blood, alveolar air, environmental air (within 1 m on the water surface). 4) Hygiene Institute, 1 hour after the end of the swimming time: samples of alveolar air, environmental air. 5) Hygiene Institute, 30 min after the previous sampling: samples of alveolar air, environmental air. Spirometric parameters have been evaluated in every subject, after resting and swimming (point 2 and 3). CHCl3 uptake has been calculated using the following formula: U = V(CI--CA)t where: U = uptake (microgram/h) V = pulmonary ventilation (l/min) CI = inspired (environmental) concentration (microgram/m3) CA = alveolar concentration (microgram/m3) t = exposure time (min) CHCl3 levels after swimming always appeared quite high; however low levels were evidenced also before exposure (point 1).(ABSTRACT TRUNCATED AT 400 WORDS)

There is a general agreement that children are a population at increased risk with respect to lead and cadmium exposure and to adverse health effects resulting from increased exposure. Different biological indicators such as blood hair and teeth have been used to evaluate lead and cadmium exposure in humans. However, up to date, it has not been established which is the best indicator to provide an assessment of internal exposure. The aim of the present study was to examine the levels of lead and cadmium in hair, blood and teeth of children living from birth in an industrialized area near Modena. The relationship between these indicators of exposure and children characteristics such as sex, weight, height, blood pressure and smoking habits of parents was also examined. 142 children (71 males and 71 females) representing 20.8% of those aged 6-7 years living in Sassuolo (Modena) have been included in the study. The geometric means of lead in blood, hair and teeth were 11.2 micrograms/dl, 7.24 micrograms/g and 6.16 micrograms/g, respectively. Hair lead were significantly related to both blood and teeth values (r = 0.226, p = 0.007 and r = 0.186, p = 0.027, respectively). Mean cadmium concentrations were 0.47 mu/l in blood, 0.17 micrograms/g in hair and 47.9 ng/g in teeth and no significant correlation was observed between the three biological matrixes examined. Significant correlations were found between lead and cadmium in both hair (r = 0.427, p = 0.000) and teeth (r = 0.224, p = 0.007). In addition, for lead content in teeth, a significant difference between boys and girls was observed; females showed higher values than males (6.77 micrograms/g vs 5.61 micrograms/g; t = 2.23 p = 0.028). Taking into account the individual characteristics of children, a negative relationship was found between Pb levels in teeth and height (r = -0.217, p = 0.024). Systolic blood pressure values were positively associated to cadmium hair levels in males but not in females (r = 0.281; p = 0.053). From the results of the present study it appears that blood, hair and teeth provide different information to predict lead and cadmium exposure of children. Hair seem to be a useful global indicator of total environmental pollution.

This study surveyed 237 schoolchildren in a lead-polluted industrial area in northern Italy to assess the relationship between various biological indicators (lead in blood, hair and teeth, and delta-aminolevulinic dehydratase [ALA-D] activity) and some neuropsychological functions, assessed by a battery of five psychometric tests. The geometric means of lead measured in blood, hair and teeth were 10.99 micrograms/dl, 6.79 micrograms/g and 6.05 micrograms/g, respectively. Mean ALA-D activity was 51 mU/ml RBC. By analysis of covariance, after regressing out the variance accountable to confounding variables (age, sex, occupation/education of parents), Total and Verbal WISC-R IQ and Toulouse Pieron test results were significantly affected by the levels of lead in teeth. ALA-D values also appeared to be related to WISC-R IQ results (Total, Verbal and Performance).