Semi-volatile organic compounds in the air and dust of 30 French schools: a pilot study.

The contamination of indoor environments with chemical compounds released by materials and furniture, such as semi-volatile organic compounds (SVOCs), is less documented in schools than in dwellings-yet children spend 16% of their time in schools, where they can also be exposed. This study is one of the first to describe the contamination of the air and dust of 90 classrooms from 30 nursery and primary schools by 55 SVOCs, including pesticides, phosphoric esters, musks, polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), phthalates, and polybromodiphenylethers (PBDEs). Air samples were collected using an active sampling method, and dust samples were collected via two sampling methods (wiping and vacuum cleaning). In air, the highest concentrations (median >100 ng/m3 ) were measured for diisobutyl phthalate (DiBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and galaxolide. In dust, the highest concentrations (median >30 µg/g) were found for DEHP, diisononyl phthalate (DiNP), DiBP, and DBP. An attempt to compare two floor dust sampling methods using a single unit (ng/m²) was carried out. SVOC concentrations were higher in wiped dust, but frequencies of quantification were greater in vacuumed dust.

Volatile and semi-volatile organic compounds of respiratory health relevance in French dwellings.

Over the last decades, the prevalence of childhood respiratory conditions has dramatically increased worldwide. Considering the time spent in enclosed spaces, indoor air pollutants are of major interest to explain part of this increase. This study aimed to measure the concentrations of pollutants known or suspected to affect respiratory health that are present in dwellings in order to assess children's exposure. Measurements were taken in 150 homes with at least one child, in Brittany (western France), to assess the concentrations of 18 volatile organic compounds (among which four aldehydes and four trihalomethanes) and nine semi-volatile organic compounds (seven phthalates and two synthetic musks). In addition to descriptive statistics, a principal component analysis (PCA) was used to investigate grouping of contaminants. Formaldehyde was highly present and above 30 µg/m(3) in 40% of the homes. Diethyl phthalate, diisobutyl phthalate, and dimethylphthalate were quantified in all dwellings, as well as Galaxolide and Tonalide. For each chemical family, the groups appearing in the PCA could be interpreted in term of sources. The high prevalence and the levels of these compounds, with known or suspected respiratory toxicity, should question regulatory agencies to trigger prevention and mitigation actions.

[How molecular biology can improve the clinical diagnosis of gliomas?] / Comment la biologie moléculaire améliore le diagnostic clinique des gliomes?

Gliomas are the most common primary brain tumors and include different diagnoses associated with a different prognosis. Histology remains the gold standard for the diagnosis of these tumors. However, pathologists may encounter diagnostic difficulties due to tumor heterogeneity or to the small size of the samples. Recently, major advances in discovery of molecular alterations of these cancers have led to the development of new molecular markers, some with a diagnostic role, others with a prognostic impact and / or predictive of therapeutic response. The testing of different molecular alterations such as 1p / 19q codeletion, mutations of IDH genes, p16 deletion, EGFR amplification or MGMT promoter methylation has been included in the daily practice in order to confirm the diagnosis, assess the patient prognosis and guide treatment choices.

Les gliomes représentent les tumeurs cérébrales primitives les plus fréquentes et regroupent différentes entités au pronostic très différent. L'examen anatomopathologique est le gold standard pour le diagnostic de ces tumeurs. Cependant, les pathologistes peuvent rencontrer des difficultés diagnostiques dues, entre autres, à l'hétérogénéité tumorale ou à la petite taille des prélèvements. Nous avons assisté, ces dernières années, à des avancées majeures dans la découverte des altérations moléculaires de ces cancers, ce qui a mené au développement de nouveaux marqueurs moléculaires, certains avec un rôle diagnostique, d'autres avec un impact pronostique et/ou prédictif de la réponse thérapeutique. Dans la pratique quotidienne, il est donc devenu utile de tester la présence de différentes altérations moléculaires telles que la codélétion 1p/19q, les mutations des gènes IDH, la délétion du gène CDKN2A/p16, l'amplification du gène EGFR ou la méthylation du promoteur du gène MGMT, afin de confirmer le diagnostic, d'évaluer le pronostic des patients ainsi que d'orienter les choix thérapeutiques.

[Next generation sequencing]. / Une nouvelle technologie pour améliorer le diagnostic des cancers thyroïdiens.

Fine needle aspiration is the gold standard method to differentiate benign thyroid nodules from malignant. However, for 15 to 30% of the cases the cytological diagnosis is indeterminate, leading to surgery. Integration of new molecular markers is opening new perspectives in order to increase the diagnostic precision of thyroid nodules with an indeterminate cytology.

La méthode diagnostique de référence pour différencier les nodules thyroïdiens bénins des nodules malins est la ponction écho-guidée à l'aiguille fine. Cependant dans 15 à 30 % des cas le diagnostic cytologique est indéterminé, menant à une intervention chirurgicale. L'intégration de nouveaux marqueurs moléculaires nous ouvrent de nouvelles perspectives pour augmenter la précision diagnostique des nodules thyroïdiens de diagnostic cytologique indéterminé.

Measurements of semi-volatile organic compounds in settled dust: influence of storage temperature and duration.

Indoor dust samples cannot always be analyzed immediately after collection. However, little information is currently available on how storage conditions may affect measurements. This study was designed to determine how sample storage conditions may affect the concentration of semi-volatile organic compounds (SVOCs) in the dust. A composite dust was prepared using a Standard Reference Material (SRM 2585) with real indoor dust samples. The composite dust was stored in various types of packaging, at different temperatures (-18°C, 5°C, 20°C, and 35°C), and in different light conditions. The concentration of SVOCs was measured after various storage durations. No effect on SVOC concentrations was observed for the composite dust stored in an amber glass vial at -18°C for 36 months. At 5°C, 20°C, and 35°C, losses occurred for the more volatile compounds. The experimental storage conditions clearly showed that temperature and duration affected the concentrations of SVOCs in the composite dust. The type of packaging material (polyethylene zip bag or polyethylene garbage bag) did not seem to have a systematic effect on the preservation of SVOCs in the composite dust. Maximum storage duration times are proposed for each compound at various temperatures. For most compounds, samples can be stored for 2 months at 20°C. For samples that cannot be analyzed immediately, we recommend to store them in the dark at -18°C to ensure a good recovery of all tested compounds.

Pesticide exposure of non-occupationally exposed subjects compared to some occupational exposure: a French pilot study.

Data about non-dietary exposure to different chemical classes of pesticides are scarce, especially in France. Our objective was to assess residential pesticide exposure of non-occupationally exposed adults, and to compare it with occupational exposure of subjects working indoors. Twenty unexposed persons, five gardeners, seven florists and nine veterinary workers living in Paris area were recruited. Nineteen residences, two greenhouses, three florist shops and three veterinary departments were then sampled. Thirty-eight insecticides, herbicides and fungicides were measured in indoor air with an air sampler for 24 h, and on hands by wiping them with isopropanol-wetted swabs. After extraction, samples were analysed by gas and high-performance liquid chromatography. Seventeen different pesticides were detected at least once in indoor air and twenty-one on the hands. An average of 4.2+/-1.7 different pesticides was detected per indoor air sample. The organochlorines lindane, alpha-endosulfan and alpha-HCH were the most frequently detected compounds, in 97%, 69% and 38% of the samples, respectively. The organophosphates dichlorvos and fenthion, the carbamate propoxur and the herbicides atrazine and alachlor were detected in more than 20% of the air samples. Indoor air concentrations were often low, but could reach 200-300 ng/m(3) in residences for atrazine and propoxur. Propoxur levels significantly differed between the air of veterinary places and other places (Kruskal-Wallis test, p<0.05) and dieldrin levels between residences and workplaces (p<0.05). There was a greater number of pesticides on hands than in air, with an average of 6.3+/-3.3 different pesticides detected per sample, the most frequently detected being malathion, lindane and trifluralin, in more than 60% of the subjects. Maximal levels (up to 1000-3000 ng/hands) were observed either in the general population or in workers, depending on the pesticide. However, no significant difference was observed between workers and general population handwipe pesticide levels. As expected, gardeners were exposed to pesticides sprayed in greenhouses. Florists and veterinary workers, whose pesticide exposure had not been described until now, were also indirectly exposed to pesticides used for former pest control operations. Overall, general population was exposed to more various pesticides and at levels sometimes higher than in occupational places. The most frequent pesticides in residences were not the same as in US studies but levels were similar. These preliminary results need to be confirmed in a greater number of residences from different parts of the country, in order to better assess pesticide exposure of the general population and its influencing factors.

Insecticide urinary metabolites in nonoccupationally exposed populations.

The wide use of insecticides in agricultural and residential settings has resulted in environmental contamination, leading to increased concern about exposure of the population and possible chronic effects on health. This review summarizes the studies that have measured urinary metabolites to assess exposure of nonoccupationally exposed population to nonpersistent insecticides, organophosphates (OPs), carbamates, and pyrethroids. Electronic search yielded 36 different studies performed in a small number of countries for the last 20 years, most of them dealing with OP urinary metabolites. Dialkylphosphates, specific metabolites of OPs, and specific metabolites of pyrethroids or carbamates, have been investigated. Results indicate that a wide range of the population, adults as well as children, is exposed to OPs and to a lesser extent to pyrethroids and carbamates. Levels are one to several orders of magnitude lower than those in occupational studies. The contribution of the different sources of insecticide exposure remains uncertain. Food contamination, as well as environmental and residential contamination, appears to influence exposure, especially in the case of children. Residential use of insecticides, having pets, and living near gardens or fields have all been inconstantly related to higher urinary metabolite levels. Occupational exposure of the parents, especially of the agricultural workers, seems to be a predictive factor of higher exposure of their children. More studies investigating every source and pathway of exposure of randomized population samples and in other countries than the United States, in particular in developing countries, could improve our knowledge of factors influencing insecticide exposure of the population.

Phenotypic characteristics of rabbit intervertebral disc cells. Comparison with cartilage cells from the same animals.

STUDY DESIGN: Intervertebral disc cells were extracted from the surrounding matrix, and their metabolic activities and phenotypes were studied. OBJECTIVES: To compare the metabolic activities and phenotypes of cell populations extracted from the intervertebral discs of young rabbits with those of articular and growth plate chondrocytes from the same animals. SUMMARY OF BACKGROUND DATA: The phenotype of intervertebral disc cells has been poorly studied and still is debated. METHODS: The intervertebral discs as well as articular and vertebral growth plate cartilage of rabbits were digested enzymatically. The morphology of freshly isolated cells was examined. Their contents of collagen II and X mRNAs were determined by Northern blot analysis, and their sulfation activity by 35S-sulfate incorporation as chondrocytic markers. Cells were cultured at high density or low density and grown in primary culture. The stability of their phenotype was monitored by evaluating the collagen I and II mRNA ratio. The proteoglycans newly synthesized by the cells also were quantified, and their elution profile analyzed on Sepharose 2B columns. RESULTS: The anulus fibrosus cells were morphologically undistinguishable from articular chondrocytes. The nucleus pulposus contained mainly large vacuolated cells and a few smaller cells. All freshly extracted cells expressed different levels of collagen II mRNA. Anulus fibrosus and nucleus pulposus cells contained, respectively, 22% and 8% of collagen II mRNA compared with that found in articular or growth plate chondrocytes from the same animal. Only growth plate chondrocytes expressed collagen X. When anulus fibrosus cells were incubated for 48 hours at high density, they had collagen II mRNA contents similar to those of articular and growth plate chondrocytes, but synthesized five to six times fewer sulfated proteoglycans. When seeded at low density, anulus fibrosus cells divided more slowly than articular chondrocytes and incorporated four times fewer 35S-sulfate into proteoglycans. Their collagen II mRNA content was 2.75-fold lower than that of chondrocytes, and the procollagen alpha 1II/alpha 1I mRNA ratio was 3.1 for anulus fibrosus cells and 7 for chondrocytes. No collagen X mRNA was detected. When incubated for 48 hours at high density, the nucleus pulposus giant cells had four times less collagen II mRNA content than cartilage cells but synthesized the same amounts of sulfated proteoglycans. They did not divide during 21 days in culture and still contained collagen II mRNA but no collagen X mRNA. CONCLUSIONS: Findings showed that intervertebral disc cells all express cartilage-specific matrix proteins with quantitative differences, depending on their anatomic situation. It is suggested that anulus fibrosus cells are chondrocytic cells at a different stage of differentiation than articular and growth plate chondrocytes. The phenotype of nucleus pulposus cells still is unclear. They could be chondrocytic or notochordal. A definitive answer to this important question requires differentiating markers of notochordal cells.

Callus response to micromovement during elongation in the rabbit.

The purpose of this investigation was to determine whether induced micromovement during the elongation period could improve the consolidation of diaphyseal elongation obtained by callus distraction. Two series of paired rabbit hindlimbs were studied. The surgical procedure and the waiting period were identical. During elongation, one hindlimb was stimulated, and the other was the control. The consolidation period was 2 days. Reproducible tibial osteotomy and lengthening of the two tibiae was confirmed radiographically. The mineralized callus was quantified by dual-beam x-ray absorptiometry. The callus diameters were measured. Bones were axially compressed to failure. Callus volume, mineral quantity, mineral density, and resistance to failure were not different on the stimulated side compared with the unstimulated side, so micromovement applied during elongation had no effect on bone consolidation. For all tibiae, resistance to failure of the callus was significantly correlated to callus volume, to callus mineral content, and to callus mineral density.

Callus response to micromovement after elongation in the rabbit.

The purpose of this investigation was to determine whether induced micromovement could improve the consolidation of diaphyseal elongation by callus distraction. Two series of paired rabbit hindlimbs were studied. The surgical procedure, waiting period, and elongation period were identical. One hindlimb was then left under neutralization conditions, but the other limb was stimulated by axial micromovements. Reproducible tibial osteotomy and lengthening of the two tibiae were confirmed radiographically. The mineralized callus was quantified by dual-beam x-ray absorptiometry. The anteroposterior and lateral diameters of the callus were measured. A semiquantitative histologic study allowed the ratio between fibrous or cartilaginous callus or both and mineralized callus to be determined. Bones were axially compressed to failure. Callus volume, callus mineral content, callus mineral density, and mechanical forces required to failure were significantly superior on the stimulated side compared with the neutralized side, so micromovements applied after the end of elongation were beneficial for bone healing. Mechanical forces required to failure were significantly correlated to callus volume and callus mineral density.

Inhibition of chondrocyte cathepsin B and L activities by insulin-like growth factor-II (IGF-II) and its Ser29 variant in vitro: possible role of the mannose 6-phosphate/IGF-II receptor.

Lysosomal enzymes and IGF-II both bind to the mannose 6-phosphate (M6P)/IGF-II receptor. This receptor targets newly synthesized lysosomal enzymes to lysosomes. The functional meaning of IGF-II binding to this receptor is not well known. We have postulated that IGF-II, the Ser29 IGF-II variant (vIGF-II) and IGF-I on lysosomal cathepsin B and L activities from post-natal rabbit chondrocytes in vitro. This effect was compared with the ability of each peptide to stimulate chondrocyte-sulfated proteoglycan synthesis. The sulfating dose-response relationship of the IGF peptides corresponded to their relative binding affinities for the type I-IGF receptor (IGF-I > IGF-II > vIGF-II). The intracellular cathepsin B and L activities were inhibited in a time- and dose-dependent manner by IGF-II or vIGF-II. Maximal inhibition of cathepsin B and L activities (40 and 30% below controls, respectively) was found after an 8 h treatment with 100 ng/ml IGF-II or vIGF-II. By contrast, IGF-I up to 1 micrograms/ml or insulin up to 2 micrograms/ml had no inhibitory effect. The relative potency pattern corresponded to the binding profile of each ligand for the M6P/IGF-II receptor. A treatment of chondrocytes with IGF-I or insulin transiently increased the binding of radiolabelled IGF-II at the cell surface to approximately 120% of controls, whereas IGF-II or vIGF-II had no effect. Thus, it is unlikely that the inhibition of lysosomal enzyme activities by IGF-II peptides could result from a redistribution of M6P/IGF-II receptors from intracellular compartments to the plasma membrane. We hypothesize that internalized IGF-II peptides could occupy the intracellular M6P/IGF-II binding sites required for targeting of cathepsins B and L to lysosomes.

Possible application of urinary analysis to estimate dissolution of some man-made vitreous fibers.

A preliminary study at the institut National de l'Environnement Industriel et des Risques (INERIS) examined the dissolution of three man-made vitreous fiber samples (glasswool, rockwool, glass microfibers: JM 100) after intraperitoneal injections in male Wistar rats. The chemical composition of the original fibers was determined by inductively coupled plasma spectrometry (ICP). The urine of the rats was collected at fixed times between day 1 and day 204, and the ICP was used to look for elements known to be present in the original fibers. At day 204, a piece of omentum was removed at autopsy, ashed and analyzed by energy dispersive X-ray analysis (EDXA) to identify the elements remaining in the fibers. Silicon and aluminium were retained in the fibers from all samples at day 204. Losses in calcium, sodium, magnesium, and sulfur were observed, but these elements were not studied in the urine samples because they are naturally present in relatively high concentrations in rat cells and biological fluids. Although there was a loss of zinc from the glass microfibers, no corresponding difference was observed between the zinc levels excreted by the treated animals and by the controls. Similarly, despite the loss of manganese from the rockwool fibers at day 204, none was detectable in the urine samples. Titanium, present at the 0.3% level in rockwool, was not detectable by EDXA at day 204, but small quantities were detected in the first 2 weeks in the urine samples of rats treated with rockwool.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atmospheric asbestos pollution in the urban environment: Rome, Orbassano and a control locality (II)]. / L'inquinamento atmosferico da amianto nell'ambiente urbano: Roma, Orbassano e località di controllo (II parte).

To complete our previous study which evaluated by TEM the atmospheric concentrations of asbestos in the urban areas of Milan, Casale Monferrato, Brescia, Ancona, Bologna and Florence, the concentrations measured in Rome, Orbassano and in two mountain test locations, one with serpentine rock (Valle di Susa) and the other with granitic rock (Adamello), are now reported. Compared with the towns in northern Italy, which had already shown decreasing pollution levels from Casale Monferrato to Milan, Brescia, Ancona, Bologna and Florence, the levels measured in Rome were extremely low, about ten times lower than those measured in Florence, which were in turn ten times lower than those measured in Milan. In Orbassano the levels near serpentine quarries were slightly higher than the geologic background values. The geologic background level in Valle di Susa was approximately 1 fibre/litre (> 5 microns) and 2.5 fibres/litre (total fibres); asbestos fibres were totally absent in the mountain area with granitic rock. The clearly decreasing values of pollution starting from the northern cities down to Rome lead to the exclusion of motor vehicle traffic as one of the "primary" sources of fibre dispersion. In fact, traffic becomes significant in producing pollution only in the presence of other dispersion sources since it gives rise to "secondary" pollution consisting of ultra-thin fibres through grinding of coarse fibres dispersed from other sources and sedimented on the ground. The authors attribute the main responsibility in maintaining comparatively high concentrations of asbestos fibres in the urban areas of northern Italy to weathered asbestos-cement coverings which act as "primary" sources.

Bone and cartilage responsiveness to sex steroid hormones.

Gonadal steroids influence the skeletal growth and metabolism both during the pubertal growth spurt and in adulthood with aging. It is now generally agreed that sex steroid effect on skeletal tissues is due to indirect and direct actions. In this presentation, in vitro effects of sex steroids on cartilage cells are reported by comparison with those observed on bone cells.

Age-dependent responsiveness of rabbit and human cartilage cells to sex steroids in vitro.

Rabbit epiphyseal cartilage tissue has been shown to convert testosterone (T) to dihydrotestosterone (DHT). In this report, the metabolic conversion of T into DHT is shown to be age-dependent, being most active in cartilage from animal at the age of gonadal maturation. Human cartilage from newborn and prepubertal children is also shown to convert T into DHT and--to a lesser extent--to estradiol. Low concentrations of DHT and 17 beta-estradiol (E2) (10(-11)-10(-9) M) were also shown to stimulate in vitro cartilage cells from boys and girls respectively. As previously shown for cultured rabbit chondrocytes, the stimulating effects of both hormones on human chondrocytes was age-dependent. Cartilage cells derived from children up to one year old did not respond, while cells from boys and girls in the early phase of puberty responded best. These data indicate that human cartilage tissue in vivo, contains both 5 alpha-reductase and aromatase activities during post-natal skeletal growth. Androgens may act on cartilage after their metabolic conversion to estrogens. The mechanism of age-dependency of both cartilage androgen enzymatic activities and chondrocyte responsiveness to sex steroids in vitro remains to be explained.

Evidence for a direct in vitro action of sex steroids on rabbit cartilage cells during skeletal growth: influence of age and sex.

A direct effect of sex steroid hormones on in vitro cartilage cell metabolism was demonstrated. Cells were derived from rabbit fetuses on day 20 of gestation, and from male and female rabbits aged from 2 to 80 days. Testosterone (T), dihydrotestosterone (DHT), or 17 beta-estradiol (E2) (10(-9) -10(-9) M) were added to primary culture of epiphyseal articular chondrocytes. They showed an age-dependent stimulatory effect on [35S]sulfate incorporation into newly synthesized proteoglycans. In cultured rabbit fetal cartilage cells, the maximum active concentration of T and DHT was 10(-9) M with a 40% stimulating effect over control values. E2 was even more active with 80% stimulating effect when added at 10(-8) M. Chondrocytes from animals aged up to 5 days responded poorly and those from animals aged 5-30 days not at all. The response of cells from older animals varied with animal age and sex. T and DHT stimulated chondrocytes from males aged 32-55 days and females aged 40-52 days to about the same extent. E2 stimulated cells from animals of the same ages, but the response of female-derived cells was twice that of male-derived cells. The stimulating effect was dose dependent from 10(-11) to 10(-8) M and maximal at 10(-9) M for T and DHT and at 10(-8) M for E2. Puromycin completely abolished the effect.

Tendon adaptation to different long term stresses and collagen reticulation in soleus muscle.

Leg immobilization with or without soleus muscle denervation was studied in young rabbits. Muscle and tendon were maintained in extension, i.e., in the most lengthened position. Length measurements performed on sarcomeres, muscle fibers and tendon-plus-muscle complexes suggest the following progression in tendon growth rates: normal less than denervated-extended less than innervated-extended. Collagen reticulation was studied as a function of fiber location along these tendons by measuring hydrothermal isometric tension (HIT). Large variations were observed depending on fiber location, and significant modifications were induced by immobilization in extension. The results are discussed in relation to stress as a possible factor controlling collagen maturation in connective tissues.

Tendon adaptation to bone shortening.

The ability of tendon to adapt its length to imposed conditions was tested in rat soleus. Shortening of one tibia left tendon insertions intact, but reduced the distance between them. Tendon lengths were found to decrease after a short period of recovery (1 or 2 months) whether surgery was performed in young or adult animals. Comparison of tibia and tendon length correlation in control rats of different ages and in experimental animals showed that adaptation was more complete in young rats than in adult rats. A long period of recovery seemed to improve adaptation only in young rats. Hydrothermal isometric tension measurements indicated that collagen remodeling occurred during tendon adaptation to bone length, with the process being more marked at the muscle-tendon junction.