Seated postural neck and trunk reactions to sideways perturbations with or without a cognitive task.

Driving on irregular terrain will expose the driver to sideways mechanical shocks or perturbations that may cause musculoskeletal problems. How a cognitive task, imposed on the driver, affects seated postural reactions during perturbations is unknown. The aim of the present study was to investigate seated postural reactions in the neck and trunk among healthy adults exposed to sideways perturbations with or without a cognitive task. Twenty-three healthy male subjects aged 19-36 years, were seated on a chair mounted on a motion system and randomly exposed to 20 sideways perturbations (at two peak accelerations 5.1 or 13.2m/s(2)) in two conditions: counting backwards or not. Kinematics were recorded for upper body segments using inertial measurement units attached to the body and electromyography (EMG) was recorded for four muscles bilaterally in the neck and trunk. Angular displacements (head, neck, trunk and pelvis) in the frontal plane, and EMG amplitude (normalised to maximum voluntary contractions, MVC) were analysed. The cognitive task provoked significantly larger angular displacements of the head, neck and trunk and significantly increased EMG mean amplitudes in the upper neck during deceleration, although 10% of MVC was never exceeded. A cognitive task seems to affect musculoskeletal reactions when exposed to sideways perturbations in a seated position.

Neck pain combined with arm pain among professional drivers of forest machines and the association with whole-body vibration exposure.

The purpose of this study was to investigate the existence of neck pain and arm pain among professional forest machine drivers and to find out if pain were related to their whole-body vibration (WBV) exposure. A self-administered questionnaire was sent to 529 forest machine drivers in northern Sweden and the response was 63%. Two pain groups were formed; 1) neck pain; 2) neck pain combined with arm pain. From WBV exposure data (recent measurements made according to ISO 2631-1, available information from reports) and from the self-administered questionnaire, 14 various WBV exposure/dose measures were calculated for each driver. The prevalence of neck pain reported both for the previous 12 months and for the previous 7 d was 34% and more than half of them reported neck pain combined with pain in one or both arms. Analysis showed no significant association between neck pain and high WBV exposure; however, cases with neck pain more often experienced shocks and jolts in the vehicle as uncomfortable. There was no significant association between the 14 WBV measures and type of neck pain (neck pain vs. neck pain combined with arm pain). It seems as if characteristics of WBV exposure can explain neither existence nor the type of neck pain amongst professional drivers of forest machines. The logging industry is important for several industrialised countries. Drivers of forest machines frequently report neuromusculoskeletal pain from the neck. The type of neck pain is important for the decision of treatment modality and may be associated with exposure characteristics at work.

Effects on leg muscular performance from whole-body vibration exercise: a systematic review.

The purpose of this study was to investigate the effects on leg muscular performance from whole-body vibration exercise. Literature search was performed on the databases Pubmed, Cinahl, ISI web of science (Sci-expanded, SSCI) and Embase (Rehab & Physical Med). Rating of 19 relevant studies was performed (14 on long-term exercise and five on short-term exercise) using a score system for the methodological quality. Several randomized-controlled trial studies of high to moderate quality show similar improvements from long-term regimen on muscular performance in the legs after a period of whole-body vibration exercise. As there were few studies on short-term exercise and as they had no control groups, the same convincing improvements regarding muscular performance were not achieved. Preliminarily, there is strong to moderate evidence that long-term whole-body vibration exercise can have positive effects on the leg muscular performance among untrained people and elderly women. There is no clear evidence for effects on muscular performance after short-term vibration stimuli.

Different toxic, fibrogenic and mutagenic effects of four commercial quartz flours in the rat lung.

There is still intensive debate on the variability in the biological activities of different quartz species. Therefore we examined in a rat lung model the inflammatory, fibrogenic and genotoxic characteristics of four commercial quartz flours. The samples, two with probably low activity and two with probably high activity were selected from a panel of 16 samples on the basis of in vitro investigations. Rats were exposed by a single intratracheal injection of 0.6, 1.2 and 2.4 mg quartz samples per lung or with 1.2 mg standard quartz DQ12. After 90 days the inflammatory response was measured in the bronchoalveolar lavage fluid, as well as the content of 8-oxoguanine in the DNA of the lung cells. Additionally mutated p53 protein was determined. The four quartz samples revealed specific differences in all parameters investigated. In good agreement with the in vitro results the two samples expected as lowly active showed only weak inflammatory and no genotoxic reactions in the rat lungs. In contrast the two samples suspected as highly reactive induced a pronounced inflammatory response and for one of the samples genotoxic effects could be proven. The results raised here show a broad spectrum of biological activities dependent on the type of quartz from almost inert to genotoxic and highly inflammatory.

Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated.

TiO(2) is considered to be toxicologically inert, at least under nonoverload conditions. To study if there are differences in lung effects of surface treated or untreated TiO(2) we investigated the inflammatory and genotoxic lung effects of two types of commercially available TiO(2) at low doses relevant to the working environment. Rats were exposed by instillation to a single dose of 0.15, 0.3, 0.6, and 1.2 mg of TiO(2) P25 (untreated, hydrophilic surface) or TiO(2) T805 (silanized, hydrophobic surface) particles, suspended in 0.2 ml of physiological saline supplemented with 0.25% lecithin. As control, animals were instilled with the vehicle medium only or with a single dose of 0.6 mg quartz DQ12. At days 3, 21, and 90 after instillation bronchoalveolar lavage was performed and inflammatory signs such as cells, protein, tumor necrosis factor-alpha, fibronectin, and surfactant phospholipids were determined. Additionally, 8 microm frozen sections of the left lobe of the lung were cut and stored at -80 degrees C. The sections were used for immunohistochemical detection of 8-oxoguanine (8-oxoGua) by a polyclonal antibody in the DNA of individual lung cells. In the quartz-exposed animals a strong progression in the lung inflammatory response was observed. Ninety days after exposure a significant increase in the amount of 8-oxoGua in DNA of lung cells was detected. In contrast, animals exposed to TiO(2) P25 or TiO(2) T805 showed no signs of inflammation. The amount of 8-oxoGua as a marker of DNA damage was at the level of control. The results indicate that both types of TiO(2) are inert at applicated doses.

Quartz exposure of the rat lung leads to a linear dose response in inflammation but not in oxidative DNA damage and mutagenicity.

Exposure to quartz and high concentrations of other poorly soluble particles can lead to the development of lung tumors in the rat. The mechanisms involved in particle-induced carcinogenesis seem to include inflammation-associated production of reactive oxygen species (ROS) and DNA damage. ROS induce 8-oxoguanine (8-oxoGua) and a panel of other oxidation products in DNA. In proliferating cells such DNA lesions can lead to various types of mutations, which might be critical for cancer-related genes with respect to tumor formation. Quartz is known to mediate the induction of 8-oxoGua in the nuclear DNA of lung cells when applied to the lung of rats. We have investigated the time- and dose-dependent biologic effects of quartz and, as a control, corundum, on cell proliferation and various pulmonary inflammation and toxicity markers in rat bronchoalveolar lavage fluid (BALF); on the induction of 8-oxoGua in the DNA of rat lung cells; and on the cellular levels of p53 wild-type and p53 mutant (mut) protein. Rats were exposed by intratracheal instillation to various amounts of quartz (0.3, 1.5, or 7.5 mg/rat) or corundum (0.3, 1.5, or 7.5 mg/rat) and measured at Days 7, 21, and 90 after exposure. Corundum had no adverse effects except a slight elevation of 8-oxoGua at a dose of 7.5 mg/rat. However, significant changes in the BALF were detected at all quartz doses. 8-oxoGua was significantly increased only at 1.5 and 7.5 mg quartz/rat. The amount of cells with detectable p53 wild-type protein levels was increased at 1.5 and 7.5 mg quartz/rat at 7 and 21 d. Elevated amounts of cells with enhanced p53 mut protein levels were measured at all time points after instillation of 7.5 mg quartz/rat.

Light and electron microscopic investigation of the lectin-binding pattern in the oxyntic gland region of bovine abomasum.

For the first time the expression of glycoconjugate residues in the oxyntic gland region of bovine abomasum has been investigated by means of lectin histochemistry. For light microscopic investigations, a battery of ten lectins, Con A, PSA, UEA I, WGA, LEA, SNA, RCA120, MPA, DBA and SBA was used. For electron microscopic examinations, WGA and RCA120 were utilized. The staining pattern of the lectins in all exocrine cell types of the oxyntic gland region is described. Compared to the results of monogastric species our study reveals some similarities, but just as many differences in the composition of glycoconjugate residues in bovine exocrine cell types. Typical for surface mucous cells is the amount of L-fucose, N-acetyl glucosamine residues and Galbeta1, 4GlcNAc sequences in the secretory granules. SNA could serve as a marker for surface mucous cells, because this lectin exclusively stains the plasma membrane and the secretory granules of surface mucous cells and the extracellular mucus. L-fucose and N-acetyl glucosamine are typical for the secretory granules of mucous neck cells. In addition, the secretory granules show the highest amount of N-acetyl galactosamine residues of all exocrine cells, so that DBA and SBA are recommended as marker lectins for mucous neck cells. Most lectins strongly stain the intracellular membrane system of oxyntic cells. The cocktail of glycoconjugates in the vicinity of the HCI production site provide protection against chemical injury. In chief cells only the apical plasma membrane is more or less labeled with all lectins apart from SNA. Specific marker lectins for oxyntic cells or chief cells of the bovine have not been characterized.

Significant differences in the cellular and molecular reactions of rat and hamster lung after quartz exposure.

Exposure of rats to high doses of quartz and other insoluble isometric particles can produce lung tumors. In contrast, after exposure of such particles in hamsters no tumor outcome has been observed. Recent studies have demonstrated that the tumorigenic effect of particles is closely linked to the induction of inflammatory processes and the subsequent formation and persistence of mutagenic oxidative DNA-modifications. Species-specific differences in sensitivity to particles should therefore be reflected in the molecular reaction of the lung cells. We exposed rats and hamsters to two different doses of quartz (0.3 mg, 1.2 mg/100 g body weight) by intratracheal instillation and characterized the dose-related pattern of pulmonary inflammation (neutrophil recruitment, TNF), toxicity (protein content, surfactant phospholipids), antioxidant defence (glutathione content), mutagenicity (8-oxoguanine, p53) and proliferation. Our results clearly demonstrate a significantly higher response of the rat to quartz exposure for all determined molecular and cellular parameters. Therefore the examination of these parameters in humans would contribute to the evaluation of the relevance of rats or hamsters as models to predict particle-induced human lung cancer risk.

Evidence of a no-effect level in silica-induced rat lung mutagenicity but not in fibrogenicity.

Exposure to silica can lead to fibrosis and the development of lung tumors in the rat. Based on these animal studies and on epidemiological data, silica has been classified as a human carcinogen. The initial mechanisms have not been finally clarified, but particle-induced tumor formation is at least closely associated with inflammation, the production of reactive oxygen species (ROS) and DNA damage. We investigated the dose-dependent effects of silica on the formation of the major DNA oxidation product 8-oxoguanine (8-oxo-Gua) in rat lung cells, on p53 (p53) and p53 mutant protein (p53 mut) synthesis, as well as on the amount of the surfactant phospholipids phosphatidylinositol (PI) and phosphatidylglycerol (PG) in the bronchoalveolar lavage fluids (BALF) as indicators of fibrotic processes in the lung. Rats were exposed by intratracheal instillation to various amounts of DQ12 quartz (0.15, 0.3, 0.6, 1.2, 2.4 mg/animal) and lungs were investigated after 21 and 90 days. PG decreased and PI increased quartz dose dependently. 8-oxoGua was significantly increased only after 1.2 and 2.4 mg quartz/animal. Cells expressing p53 protein were increased at 1.2 and 2.4 mg, p53 mutant protein only at 2.4 mg/animal. This indicates a no-effect level for mutagenicity at a low, but still fibrogenic quartz exposure.

Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study.

Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid.

DNA Damage and Inflammation in the Rat Quartz Model: Differences in Inflammatory Response and Formation of Oxidative DNA Adducts to High and Low Dose of DQ12 Quartz.

Chronic exposure to poorly soluble particles such as quartz and diesel soot produces dose-dependent inflammatory responses in the rat lung. It has been shown that the inflammation in the rat lung causes persistent oxidative DNA damage and mutations in proliferation-competent cells, which are thought to be critical for tumorigenesis. In measuring various inflammatory parameters to a multidose quartz exposure in parallel with the amount of 8-oxoguanine (8-oxoGua) on the cellular level in rat lung, mechanistic data for understanding the underlying processes could be gained. Rat lungs (female Wistar, 180-220 g/bodyweight) were instilled with quartz DQ12 (doses 0.3, 1.5, and 7.5 mg/animal; controls: corundum at the same doses and physiological NaCl) and analyzed 90 days after intratracheal instillation. The bronchoalveolar lavage (BAL) fluid was determined for inflammation markers (differential cell count, protein, lung surfactant lipids, and tumor necrosis factor alpha); tissue sections of lungs were investigated for the amount of 8-oxoGua on the cellular level using an antibody against 8-oxoGua. The results reflect different responses for quartz versus all controls and show a clear dose-response relationship. Quartz elicited inflammatory reponses determined in the BAL fluid even at the low dose (0.3 mg/animal). In contrast, the level of 8-oxoGua in the lung of animals exposed to 0.3 mg quartz was not statistically increased above controls, whereas doses of 1.5 mg and 7.5 mg caused significant elevations. The data obtained indicate a no-effect level for the persistence of the mutagenic DNA adduct 8-oxoguanine in the epithelial lung cells at a low-dose quartz exposure that is still inflammatoric and fibrogenic.

Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure.

Exposure of rats to quartz (or various other particles) can lead to the development of lung tumors. At the moment, the mechanisms involved in particle-induced tumor formation are not clarified. However, it is suggested that inflammation, in conjunction with the production of reactive oxygen species (ROS) and an enhancement of epithelial cell proliferation, may play a key role in the development of lung tumors. ROS induces 8-oxoguanine (8-oxoGua) and other mutagenic DNA oxidation products, which can be converted to mutations in proliferating cells. Mutation formation in cancer-related genes is a critical event with respect to tumor formation. In this study we investigated the effects of quartz (DQ12) and of the nontumorigenic dust corundum on the induction of 8-oxoGua in the DNA of rat lung cells, as well as on cell proliferation and pulmonary inflammation. Wistar rats were exposed by intratracheal instillation to quartz (2.5 mg/rat) or corundum (2.5 mg/rat) suspended in physiological saline; control animals exposed to physiological saline or left untreated. Measurements were carried out 7, 21, and 90 days after the exposures. 8-oxoGua levels were determined in lung tissue sections at the single cell level by immunocytological assay using a rabbit anti-8-oxoGua antibody. After exposure to quartz, 8-oxoGua levels were significantly increased at all time points of investigation. Additionally, we observed inflammation and an enhanced cell proliferation. Exposure to corundum had no adverse effects on the lung; neither increased 8-oxoGua levels nor enhanced cell proliferation or inflammation were detected. These observations support the suggestion that inflammation associated with increased 8-oxoGua levels in lung cells and increased cell proliferation is an important determinant for particle-induced development of lung tumors in the rat.

Age-dependency of surfactant phospholipids and surfactant protein A in bronchoalveolar lavage fluid of children without bronchopulmonary disease.

Whilst alterations in surfactant components of bronchoalveolar lavage fluid (BALF) have been described in a variety of pulmonary diseases in adults, no information is available on the surfactant composition in children beyond the neonatal period. In order to obtain reference values for the paediatric age group, we have studied phospholipid profiles of BALF in children without pulmonary disease. The study population consisted of 38 children aged 3-15 yrs (mean +/- SD 8 +/- 4 yrs) undergoing elective surgery for nonpulmonary illnesses. Surfactant composition was analysed by high pressure liquid chromatography using both an ultraviolet and a light-scattering detector. Total phospholipid concentration was higher in children under 8 yrs of age and decreased with age. In contrast, the total protein concentration remained constant throughout the age range. No age-related changes in the relative composition of phospholipid fractions could be observed. Surfactant protein A concentrations were highly variable in all age groups. This study provides the first data on surfactant components in bronchoalveolar lavage fluid of healthy children and will be the basis for future studies of children with pulmonary diseases.

Silicotic lymph node reactions in mice: genetic differences, correlation with macrophage markers, and independence from T lymphocytes.

Quartz was injected into a hind food of BALB/c and DBA/2 mice and on days 40, 90, and 180 the progressive response ensuing in the draining popliteal lymph node (PLN) was investigated by histopathology and immunohistopathology. The area of silicotic nodules (ASN) was measured by morphometry, and, by this parameter, strain BALB/c proved to be a high responder to quartz, and strain DBA/2 a low responder, albeit both strains showed a similar degree of reactive lymphoid hyperplasia in the draining PLN. Both strains also showed a similar quartz content in the draining PLN but in BALB/c mice quartz particles were concentrated in the ASN, whereas in DBA/2 mice they were evenly dispersed over the PLN. Because the silicotic response of athymic BALB/c nu/nu mice was even stronger than that of euthymic BALB/c mice, T cells are not required for the development of silicotic nodules. This fits the notion that quartz is not an antigen and that high and low responder strains are MHC-identical. Because quartz-treated BALB/c, but not DBA/2 mice, showed a persistent expression of the macrophage differentiation markers MRP8 and MRP14, phenotypically the observed strain difference in silicotic responsiveness seems to be expressed at the level of macrophages.

Advantages of Sirius Red staining for quantitative morphometric collagen measurements in lungs.

Sirius Red staining is presented as a method for collagen determination, enabling quantitative morphometric measurements to be performed in locally defined tissue areas. The advantage of this method is especially shown for alveolar lung tissue. By excluding the bronchial areas in the tissue sections, the differences in the degree of fibrosis proved to be more discrete after different loads of quartz dust than by any other method. The difference of 12 micrograms collagen measured colorimetrically represented a 1.2-fold increase. The collagen measured in the alveolar tissue by the morphometric method rose from 9.8 to 28.6%. This is a 2.9-fold increase, underlining the vast improvement in sensitivity. Thus, this method is specifically suitable for the evaluation of very small fibrotic lesions. The quartz doses given are particularly low compared to most other investigations. Histologic lung and lymph node sections from female Wistar rats injected intratracheally with differing quantities of quartz dust (0.03, 0.1, 0.5, 1.75 mg) were stained with Sirius Red, and the collagen fibers measured with a quantitative image analysis. The results for lymph nodes using different methods (wet weight determination, quantitative measurement of quartz typical areas, colorimetric and morphometric collagen determination) showed a high correlation at the different doses. This showed that the morphometric method is suitable for the quantitative measurement of collagen. Corresponding results were also found in the comparative lung tissue measurements (colorimetric and morphometric collagen determination). However, the morphometric method has the decisive advantage that measurements can be restricted to defined tissue areas and do not destroy the section.

Toxicological investigations on silicon carbide. 1. Inhalation studies.

The question of lung damage as a result of exposure to silicon carbide (SiC) was investigated by inhalation experiments to obtain information on the qualitative response of lung tissue to the test substance (SiC). For comparison, quartz, kaolinite, and tempered clay dusts were used. The indices for the effects of the dusts studied were organ weights, numbers of bronchoalveolar cells, lung surfactant phospholipid concentrations including subfractions, and lung clearance. Exposure to the test samples was carried out according to the Essen inhalation model in two independent series. The results of the two series were similar: Compared with sham controls, exposure to SiC did not affect the indices studied. Even at a low dose (a quarter of the SiC dose) quartz gave pronounced deviations in all indices. In particular, an increase in granulocytes indicated toxic properties of the dust. The long term elimination of quartz from the lung was worse than that of SiC. The kaolinite and tempered clay dusts were intermediate between SiC and quartz based on several of the indices studied. It is concluded that SiC is deposited practically inert in the lung.