Concentrations of lead in blood, hair and saliva of German children living in three different areas of traffic density.

Lead contents in hair, whole blood and saliva were determined for 245 healthy children (121 male, 124 female, age: 8-10 years) from three residential areas of Düsseldorf (North-Rhine-Westphalia, Germany) with different traffic densities. The geometric mean for the lead content in hair was found to be 0.87 microg/g (range: 0.2-9.9 microg/g) for the entire test group. While the levels of lead in hair in the suburban population were significantly lower than in the two city centre populations, no significant difference concerning the lead content in hair could be detected in the latter. The geometric mean for lead concentration in whole blood amounted to 25.0 microg/l (range: 8.0-154 microg/l). There was no significant difference between the sub-groups. The lead concentrations found in saliva were rather low (range: < 1.5-47.0 microg/l). Of the values, 89% were below the detection limit of 1.5 microg/l. Due to reduced levels of lead in fuel, the present study exposes that the amount of lead in the children examined has further decreased compared to preceding surveys. The correlation between the lead content in hair and the road traffic density was not corroborated by the findings with regard to amounts of lead found in blood, indicating that residual lead from fuel does not result in a substantial burden of lead found in the whole body. In contrast to levels of lead found in blood, levels of lead found in hair may be influenced more by environmental conditions. Saliva is not a suitable material for biological monitoring with respect to lead exposure in children.

Mercury concentrations in urine, scalp hair, and saliva in children from Germany.

Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between <0.1 and 5.3 microg/l [geometric mean (GM) 0.26 microg/l or 0.25 microg/g creatinine; median for both, 0.22 in microg/l and microg/g, respectively]. Using multiple linear regression analysis, two predictors have been found accounting for 25.3% of the variance of mercury levels in urine: the number of teeth with amalgam fillings (23.2%) and the number of defective amalgam fillings (2.1%). The mercury content in hair ranged from <0.06 to 1.7 microg/g (GM 0.18 microg/g; median 0.18 microg/g). The frequency of fish consumption, the smoking habits of the parents, and the age of the children accounted for 20.4% of the variance of mercury levels in hair. The correlation between the hair mercury content and urine mercury concentration was low (r=0.297). Mercury levels in saliva ranged between <0.32 and 4.5 microg/l (median 0.16 microg/l). The mercury concentration in saliva was below the limit of quantification of 0.32 microg/l in more than 70% of the samples. Mercury analysis in urine is suitable to estimate mercury exposure due to amalgam fillings, whereas hair mercury better reflects mercury intake by fish consumption. Up to now, saliva does not seem to be a suitable tool to monitor the mercury burden, at least not at low exposure levels.

Cytokines detectable in saliva of children as appropriate markers of local immunity of the oral cavity--an approach for the use in air pollution studies.

The objective of this study was the detection of proinflammatory markers in saliva to be involved in local immunity of the oral cavity. Therefore saliva of 167 schoolchildren aged 8-10 years were investigated for the presence of interleukin-8 (IL-8), tumour necrosis factor alpha (TNF alpha) and soluble tumour necrosis factor receptor type II (sTNFRII). In saliva of schoolchildren sufficient quantities of IL-8 (302.3-4208.6 pg/ml), TNF alpha (0.3-40.6 pg/ml) and sTNFRII (17.6-931.3 pg/ml) were detectable. IL-8, TNF alpha and sTNFRII revealed significant correlations with each other. Results suggest an immunoregulatory mechanism of IL-8, TNF alpha and TNF-receptor to be of special concern in host defence as well as in maintaining homeostasis of local immunity within the oral cavity. Saliva provides an ideal medium for the detection of proinflammatory markers of the oral cavity with respect to mucosal and granulotype origin and may be employed in air pollution epidemiology, especially with regard to children.

Dietary intake of lead, cadmium, copper and zinc by children from the German North Sea island Amrum.

The dietary intake of metals was studied in seven male and seven female children at the age of 1.5 to 5.3 years living in a remote area of Germany, the North Sea island Amrum. The dietary intake of lead and cadmium was measured by a seven-day-duplicate study using atomic absorption spectrometry. The dietary intake of copper and zinc were calculated from food diaries. The median lead and cadmium intakes were 2.1 micrograms/(kgbw x week) [range: 0.63-5.1 micrograms/(kgbw x week)] and 2.7 micrograms/(kgbw x week) [range: 1.7-4.4 micrograms/(kgbw x week)]. The median daily intake of copper and zinc were 1.1 mg/d (range: 0.54-2.5 mg/d) and 5.7 mg/d (range: 2.7-14 mg/d). Compared to the provisional tolerable weekly intake (PTWI) of 25 micrograms/(kgbw x week) proposed by the WHO the dietary intake of lead was low. The median amounted to 8.5% and the maximum to 20% of the PTWI. The cadmium intake was comparatively high. The median amounted to 39% and the maximum to 63% of the PTWI [7 micrograms/(kgbw x week)]. The median intake of copper was in the range of the values recommended by the German Society of Nutrition (0.7-1.0 mg/d and 1.0-1.5 mg/d for children at the age of 1-< 4 years and 4-< 7 years). Twenty-three percent of the calculated intakes were below these values. The median intake of zinc however did not reach the recommended dietary intake of 7 and 10 mg/d for children at the age of 1-< 4 years and 4-< 7 years.

Prolonged reduction of salivary immunoglobulin A (sIgA) after a major academic exam.

OBJECTIVE: In a previous study we observed a continuous reduction of salivary IgA concentration ([sIgA]) during a period of academic stress. This reduction of sIgA concentration exceeded the stress period by at least 1 week. The present study aimed to replicate and extend our previous finding. In particular, we wanted to examine the time of recovery of [sIgA] alterations associated with academic stress. METHOD: Twenty-seven participants in a major medical exam and 27 controls not participating in any exam during the study provided daily saliva samples (immediately after awakening), from the 6th day prior to their last exam until the 14th day afterwards, for analysis of salivary IgA. Data were averaged for the last weeks of exams and the first and second week after exams, respectively. RESULTS: A prolonged reduction of sIgA in exam students as compared to controls was observed. Fourteen days post-stress sIgA concentrations of exam students were still significantly lower than control levels (P=0.004). No recovery was observable. At the same time exam students and controls did not differ in terms of self-reported stress and recovery. CONCLUSIONS: Psychological and immunological stress effects may be dissociated, the latter considerably exceeding the stress period. A closer look at the temporal dynamics of stress-induced immune alterations might increase our understanding of psychoimmuno relationships.

After-effects of stress on crevicular interleukin-1beta.

BACKGROUND: In a previous study, we found stress to increase crevicular interleukin-1beta (Il-1beta) secretion induced by supragingival plaque. While in that study, stress and plaque were presented concomitantly, we now wondered whether a consecutive presentation of these 2 factors would still exert stress effects. METHOD: 39 medical students participated in the study; 18 took part in a major exam while the remaining 21 served as controls. From the day after the last exam, students neglected oral hygiene in 2 antagonistic quadrants for 21 days (experimental gingivitis), while they maintained perfect hygiene at the remaining sites. Crevicular fluid samples were taken at days 0, 5, 8, 15, 18, and 21 of experimental gingivitis. RESULTS: A significant effect of pre-exposure to academic stress on crevicular Il-1beta concentration was found (area under the curve: p=0.042), the effect size, however, being smaller than in our previous study when stress and plaque were presented concomitantly. CONCLUSIONS: It is concluded that pre-exposure to stress may persistently alter the immunological effects of microbial challenge to the periodontium.

Induction of mitotic cell division distrubances and mitotic arrest by pyrethroids in V79 cell cultures.

Five pyrethroids (fenvalerate, deltamethrin, cypermethrin, permethrin, cyfluthrin) differing in their chemical purity were investigated on their cytotoxic effects, especially on their ability to induce mitotic cell division disturbances using Chinese hamster lung cells of line V79. The colony forming ability (CFA) resulted in distinct differences of the cytotoxic effect of the tested pyrethroids, whereby permethrin was found to be most toxic. With the exception of fenvalerate all tested pyrethroids gave rise to inhibition of cell cycle progression as shown by G2/M-arrest of synchronized V79 cells by flow cytometry as well as by the increase of the mitotic index as evaluated by light microscopy. The mitotic arresting activity could be attributed to the occurrence of abnormal mitotic figures such as initial and full C-metaphases. The results however indicate, that pyrethroids per se do not contribute to the cytotoxic effects but that other factors such as chemical impurities, source as well as manufacturing process and isomer composition may be responsible for the observed cytotoxic effects.

Metabolism of (S)-bioallethrin and related compounds in humans.

Chrysanthemate insecticides like (S)-bioallethrin, natural pyrethins, and related pyrethroids are subjected to extensive hydrolytic and oxidative degeneration by the mammalian metabolism, leading to a complex series of metabolites partially conjugated and finally eliminated in the urine. The major oxidation products of chrysanthemic acid, cis-(E)- and trans-(E)-chrysanthemumdicarboxcylic acid (cis-(E) and trans-(E)-CDCA), were synthesized and their structures were established by nuclear magnetic resonance spectrometry (H1-NMR) and mass spectrometry (MS). Diastereoselective separation was by high performance liquid chromatography (HPLC) and capillary gas chromatography (GC). An analytical method for extraction and identification of CDCA from human urine was developed. Quantitation was by gas chromatography and electron-impact mass spectrometry (GC/MS). The limit of detection was 20 microg/l for cis-(E)-CDCA and 10 microg/l for trans-(E)-CDCA. To test the applicability of the presented method, urine samples of humans exposed to (S)-bioallethrin were investigated. Urinary peak excretion of trans-(E)-CDCA occurred within 24 h after exposure.

The influence of individual susceptibility in pyrethroid exposure.

The aim of this study was to find a suitable biomarker for pyrethroid adverse effects. It was shown that there is a correlation between the half-life time (t(1/2)) of pyrethroids in plasma and the clinical findings. We hypothized that this finding indicates an interindividual different amount of total esterase activity or even a polymorphism. By in vitro experiments it was demonstrated that pyrethroids are cleaved by carboxylesterases. After it turned out that carboxylesterase activity in human plasma is too low for detection, a method for specific determination of carboxylesterase activity in human isolated lymphocytes was developed. As a substrate for carboxylesterase activity, cyfluthrin was added to the lymphocyte suspension. As a proof for cyfluthrin degradation by carboxylesterases the produced hydrocyanic acid was determined by GC/MS. First hints for interindividual differences in carboxylesterase activity in lymphocytes were found.

Immunological parameters in humans exposed to pesticides in the agricultural environment.

Immune parameters were examined in 224 sera of non-exposed controls and in 304 sera of pesticide applicators in the agricultural environment. In comparison to the control group pesticide applicators showed significant increased odds ratios for neopterin and soluble tumor necrosis factor receptor (sTNF RII) and a decreased odds ratio for immunoglobulin M. Obtained results indicate an enhanced macrophage activation and an impaired humoral defense. These alterations have been found to correlate with exposure duration in the group of pesticide applicators in agriculture. For subjects who worked in indoor pest control an inverse correlation for sTNF RII with exposure duration was obtained indicating impairment of cell mediated immune function. It can be concluded that exposure to pesticides in the agricultural environment may contribute to modulation of the immune system. Since immune modulating agents can potentially lead to adverse health consequences the involvement of immune biomarkers in pesticide-related health studies seems to be of considerable value for risk assessment studies.

Increase of crevicular interleukin 1beta under academic stress at experimental gingivitis sites and at sites of perfect oral hygiene.

This study analyses the effects of academic stress on crevicular interleukin-1beta(I1-1beta) both at experimental gingivitis sites and at sites of perfect oral hygiene. I1-1beta is thought to play a predominant role in periodontal tissue destruction. 13 medical students participating in a major medical exam (exam group) and 13 medical students not participating in any exam throughout the study period (control group) volunteered for the study. In a split-mouth-design, they refrained from any oral hygiene procedures in two opposite quadrants for 21 days (experimental gingivitis) while they maintained perfect hygiene levels at the remaining sites. Crevicular fluid was sampled for further I1-1beta analysis at teeth 5 and 6 of the upper jaw at days 1, 5, 8, 11, 14, 18 and 21 of the experimental gingivitis period. Exam students showed significantly higher I1-1beta levels than controls both at experimental gingivitis sites (area under the curve, exam group: 1240.64+/-140.07; control group: 697.61+/-111.30; p=0.004) and at sites of perfect oral hygiene (exam group: 290.42+/-63.19; control group: 143.98+/-42.71; p = 0.04). These results indicate that stress might affect periodontal health by increasing local I1-1beta levels especially when oral hygiene is neglected.

[Effect of microbial aerosols on the human]. / Wirkung von mikrobiellen Aerosolen auf den Menschen.

Based on numerous publications dealing with the effects of microbial emissions on workers in waste processing plants and on few papers concerning the assessment of the environmental health relevance of microbial aerosols on people living in the vicinity of composting facilities, the current state of the art in this field is presented. With regard to occupational exposure the possible health effects like infections, toxicity and allergies are specified. Since to date only few studies have been made of populations exposed to microbial aerosols in ambient air, the environmental health aspects are reviewed in the context of a study of three compost plants in Hesse, where ambient air measurements as well as epidemiological investigations were carried out. Final recommendations are given and the research needs regarding the environmental health significance of microbial aerosols are formulated.

Soluble tumor necrosis factor receptor (sTNF RII) in sera of children and traffic-derived particulate air pollution.

Tumor necrosis factor receptor (sTNF RII) was determined in sera of 160 healthy schoolchildren of the city of Düsseldorf, Germany, living in areas with different traffic density. According to the frequency distribution a higher prevalence of children with increased sTNF RII values (> 3000 pg/ml) were found for a high traffic area as compared to a low traffic area. Based on sTNF RII values above the 75% percentile of children from the low traffic area, the group of children from the high traffic area revealed a significant increased odds ratio of 2.5. Concerning traffic-derived particulate air pollution an association between the concentration of fine particles (PM2.5) and sTNF RII serum levels could be observed for both areas. Furthermore, sTNF RII values gave a significant positive correlation with C3c, an activation product of the complement component C3. C3c has been shown to be a sensitive indicator of the non-specific humoral defence in response to air pollution. Therefore, the results suggest that traffic-derived fine particles may upon inhalation trigger immune modulation via the activation of macrophages and enhanced cytokine production.

Enterotoxin and toxic shock syndrome toxin-1 production of methicillin resistant and methicillin sensitive Staphylococcus aureus strains.

In this study the production of enterotoxin A-D and toxic shock syndrome toxin-1 (TSST-1) of 181 methicillin resistant (MRSA) and 100 methicillin sensitive (MSSA) Staphylococcus aureus first isolates from different patients was investigated. All the MRSA- and MSSA isolates in the study were collected in a period between 1993 and 1995 from specimens sent from 11 different acute care hospitals in the greater Düsseldorf area. As far as possible the isolates were matched according to ward and hospital. The isolates were collected in the same time period and matched for specimen from which isolated. Furthermore, only first isolates were analysed in both groups. No significant difference in the production of toxin of any type between MRSA and MSSA could be detected (51 and 40% respectively). When the individual toxins were analysed, again no significant difference between MRSA and MSSA was demonstrable (enterotoxin production by MRSA 40% and MSSA 36%, and TSST-1 16% and 8% respectively). Despite this, a slight tendency for MRSA to produce enterotoxin A and B and for MSSA to produce enterotoxin C was observed. In addition, generation of TSST-1 by both groups was independent of enterotoxin A-D production. Interestingly, no increase in the proportion of TSST-1- or enterotoxin-producing MRSA and MSSA isolates was observed in strains isolated from blood cultures from patients with a clinical diagnosis of sepsis. Genotypical pulsed-field-gel-electrophoresis (PFGE) and phenotypical (bacteriophage typing, lysotyping) characterization of the 181 MRSA isolates resulted in 28 different PFGE patterns (of which 19 were toxin producers) and 22 lysotyping groups (18 of which produced toxin). In summary, the investigated clinical S. aureus isolates showed no difference in their ability to produce toxin and this was independent of their sensitivity to methicillin.

Methicillin resistant Staphylococcus aureus strains in the greater Düsseldorf area.

Over a period of three years the incidence of methicillin resistant Staphylococcus aureus (MRSA) isolates in 11 hospitals in the greater Düsseldorf area was observed. From a total of 7,814 S. aureus isolates, 489 (6.3%) were methicillin resistant. From 198 different patients, MRSA first isolates and 291 second isolates could be cultured. Methicillin resistance among all S. aureus isolates from 11 hospitals in the greater Düsseldorf area, ranged from 0.5 to 7.8% dependant on the size of the hospital. The highest incidence (7.8%) was found in a 1,500 bed hospital and the lowest incidence in a smaller 200 bed hospital (0.5%). With respect to the distribution among clinical departments the highest incidence of MRSA isolates was found on intensive care units and surgical wards, 25.5% and 13.0% respectively. The commonest specimen from which the MRSA isolates were cultured were respiratory secretions (17.6%) followed by central venous catheter tips (12.8%). In terms of the drug resistance pattern: all isolates were resistant to the aminoglycosides and gyrase inhibitors, whereas between 80% and 90% were sensitive to fusidic acid, chloramphenicol and pyrimethamine-sulfamethoxazole. All the strains were sensitive to the glycopeptide antibiotics, vancomycin and teicoplanin. Strain typing of 181 available first isolates (from a total of 198 first isolates) by PFGE and phage lysotyping produced identical results in more than 90% of all cases. Twenty-eight different MRSA strain types were identified by PFGE and in total 23 lysotypes could be determined. During the period of investigation an increased incidence of MRSA on an intensive care unit was observed, in which a total of 204 MRSA (42% of the total number) were isolated. The strain typing using both methods showed that on that ICU eight different MRSA types were involved in this outbreak. A hygiene plan was implemented on the unit with considerable success in reducing the incidence and spread of MRSA.

[Insertion possibility of 16S-23S space amplification and random amplified polymorphic DNA analysis for typing of methicillin-resistant Staphylococcus aureus strains in the context of nosocomial infections]. / Einsatzmöglichkeiten der 16S-23S-Spacer-Amplifikation und der "Random Amplified Polymorphic DNA"--Analyse zur Typisierung Methicillin-resistenter Staphylococcus aureus-Stämme im Rahmen nosokomialer Infektionen.

Within the scope of the present study n = 183 MRSA isolates from the extended area of Düsseldorf and n = 93 international MRSA strains from seven different countries were typed by pulsed-field gel electrophoresis and two PCR methods (RAPD and 16S-23S-spacer amplification). The isolates could be subdivided into 30 different types by PFGE, into 21 by means of RAPD and 18 by 16S-23S-spacer amplification. PFGE had the highest discriminatory potential, however, a combined use of the three typing methods allows a more detailed differentiation even of those isolates with identical PFGE pattern. Both amplification procedures were rapid, easy in handling with reproductable results. For a temporary epidemiological analysis within 24 hours, both amplification methods could be combined. In case the investigated isolates were still suspected of showing a "clonal identity", they should be analysed by additional PFGE (lasting about four days). Although the international isolates were chosen by random selection, several MRSA strains with identical pattern could be found in different countries of the world. Some RAPD-, spacer- and PFGE pattern were constant over many years. This reflects a high genetic stability of single strains.

Biological monitoring of pyrethroids in blood and pyrethroid metabolites in urine: applications and limitations.

The objective of this study was to perform biological monitoring of subjects who are occupationally exposed to pyrethroids. The study group consisted of 30 pest control operators exposed to cyfluthrin, cypermethrin or permethrin. After exposure, 24-h urine samples were collected and 20 ml of blood was drawn. The pyrethroid metabolites cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, 3-phenoxybenzoic acid and fluorophenoxybenzoic acid were determined in the urine samples (limit of detection: 0.5 micrograms/l) by GC MS and the pyrethroids in plasma (limit of detection: 5 micrograms) GC-ECD. The concentrations of metabolites in the urine of the pest control operators ranged between < 0.5 micrograms/l and 277 micrograms/l urine. The concentrations of cyfluthrin, cypermethrin and permethrin in the plasma were below the limits of detection (< 5 micrograms/l). To test if the metabolites are specific for pyrethroid exposure, they were determined in the urine of non-exposed subjects (n = 40). In no case could pyrethroid metabolites be detected. A cyfluthrin elimination experiment showed that cyfluthrin metabolites are eliminated following first-order kinetics (t 1/2 = 6.4 h). Storage experiments demonstrate that frozen urine samples (-21 degrees C) show no significant losses of metabolites within a year. In contrast, pyrethroids stored in plasma are susceptible to further biodegeneration.