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Biomedical subjects

P J Borm

Publications and source records attributed to P J Borm.

At least 19 recordsLinked to original sources

Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica.

Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.

Animals

Evaluation of urinary excretion of 1-hydroxypyrene and thioethers in workers exposed to bitumen fumes.

Biological monitoring of exposure to bitumen fumes during road-paving operations was carried out. In order to evaluate the biological uptake of the workers, the nonselective urinary thioether assay and a selective method for the determination of urinary 1-hydroxypyrene were used. Urinary thioether data of exposed workers were higher than those of nonexposed subjects. The effect of smoking, however, was stronger than the effect of occupational exposure. Levels of 1-hydroxypyrene in road-paving workers were significantly higher than those in control subjects. The 1-hydroxypyrene level was also influenced by smoking habits, but the effect of occupational exposure was stronger. Our present data suggest that enhanced urine levels of both thioethers and 1-hydroxypyrene in bitumen workers may indicate an increased genotoxic risk. Furthermore, our results demonstrate the applicability of the 1-hydroxypyrene assay after occupational exposure to petroleum-based products.

Adult

A survey of static and dynamic work postures of operating room staff.

Work in health care units is associated with considerable physical strain and many musculoskeletal complaints. Most investigations have concentrated on the work of general hospital nurses; little is known about the physical stress load on other health care workers. We therefore carried out an ergonomic study amongst operating room staff in order to (i) determine the work (posture) stress load on this particular group of health care workers and the effect of static posture on this stress, (ii) identify activities involving poor work postures, and (iii) determine differences between specialties in regard to work posture stress load. The work postures and related work activities of four different groups of staff in operating rooms (surgeons, assistant anaesthesists, instrumentation nurses and circulating nurses) were recorded and evaluated using the specified Ovako Working posture Analysing System (OWAS). Observation during the course of 18 daily surgical programmes (total number of observations: 3714) in the specialties general surgery and ear-nose-throat (ENT) surgery revealed that the work-load according to OWAS for circulating nurses and assistant anaesthesists was not harmful. Some work postures seen among instrumentation nurses and surgeons, however, need improvement. The work posture stress load in these groups is mainly due to the high prevalence of static work postures during the activities "surgery" (surgeons) and "assisting surgery" (instrumentation nurses). Significant differences in ergonomic stress load were observed between general surgeons and ENT surgeons. This survey in operating theatres relates work postures to basic activities and can be used as a starting point from which to improve work conditions in order to reduce or eliminate physical complaints among operating room staff.

Ergometry

Molecular basis for differences in susceptibility to coal workers' pneumoconiosis.

It is generally accepted that there are differences among workers in susceptibility towards the effects of mineral dusts such as silica, coal dust and asbestos. Basic research continues to find new factors involved in the process of pulmonary fibrosis caused by these minerals. In this paper, two hypotheses implicitly generated by recent findings were tested in two case-control studies among coal miners: generation of tumour necrosis factor (TNF) by blood monocytes of miners with coal workers' pneumoconiosis (CWP) and serum type III procollagen peptide (PIIIP) in CWP. Our data indicate that both parameters can be used as biological markers for early diagnosis of CWP. A follow-up study is described in which the predictive power of increased TNF release and serum PIIIP as risk factor to develop lung fibrosis will be assessed.

Adult

Composition and health hazards of water-based construction paints: results from a survey in the Netherlands.

Water-based construction paints may have beneficial effects toward man's occupational and general environment when compared to traditional paints that contain large amounts of organic solvents. The aim of this study was to describe the health hazards of the application of these alternative paints. The composition of these paints was obtained by a questionnaire survey among the main producers and importers in The Netherlands. Physicochemical parameters and toxicity data of the constituents were used to estimate occupational and environmental health hazards. Mucous membrane of skin irritation and sensitization are predicted to be the most frequently occurring health hazards after contact with these paints during professional or do-it-yourself application. Health hazards from environmental pollution may be irritation of the mucous membranes when the indoor environment is painted and fish mortality due to slowly degradable polyacrylate binders. The health hazards can be reduced by replacing some toxic compounds with less toxic ones and by hygienic (ventilation, skincare, no cleaning of application materials under the tap) measures.

Animals

Plasticisers, another burden for asthmatics?

The widely used plasticiser di(2-ethylhexyl)phthalate (DEHP) has been reported to have some toxicological effects on pulmonary tissue. Inhalation of DEHP may cause pulmonary edema and bronchial asthma. Moreover intravenous injection of DEHP induces pulmonary inflammation and hemorrhage of the lungs. We now report that DEHP might cause bronchial hyperresponsiveness. The metabolite of DEHP mono(2-ethylhexyl)phthalate (MEHP) induces in vitro a dose-dependent increase in -log EC50 for methacholine dose response curves in rat tracheal tissue. Moreover MEHP induces a decrease in maximal effect of the methacholine dose response curve. We concluded that DEHP due to the formation of MEHP in vivo, may cause bronchial hyperresponsiveness.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Setting acceptable exposure limits for toluene diisocyanate on the basis of different airway effects observed in animals.

Little epidemiological data are available to enable the development of a dose-response relationship for the effects of isocyanates, powerful sensitizing agents in humans. Remarkably, most classes of effects have been reproduced in some animal models and parallels between animals and man are impressive. In this paper animal data concerning different effects of TDI on the respiratory system were used to calculate acceptable exposure levels for humans. Animal data on respiratory irritation, sensitization, airway hyperresponsiveness, and gradual loss of pulmonary function are discussed. Two different approaches for extrapolation to man were applied to these data. The two models used to extrapolate animal data to man gave similar results. The extrapolations lead to acceptable exposure varying from 6 to 46 ppb. Most international acceptable levels for occupational airborne TDI exposure are within this range. Interestingly, the lowest standard is obtained using the data on respiratory irritation. It is, however, concluded that there is no critical (adverse) effect to define acceptable toluene diisocyanate exposure since the data were obtained from different studies and the accuracy of the applied extrapolation approach might depend on the biological effect considered. We recommend prior testing of "alternative" diisocyanates in one of the animal models described and calibrated for TDI.

Administration, Inhalation

Observations of working postures in garages using the Ovako Working posture Analysing System (OWAS) and consequent workload reduction recommendations.

The working postures of mechanics (n = 84) in 42 garages were observed using the Ovako Working posture Analysis System (OWAS). During observation, both working postures and work activities were recorded. A computer program was developed for the data analyses. Using this program it is possible to calculate the working posture load for each work activity and the contribution of a specific activity to the total working posture load. This is a substantial extension of the original OWAS method. Five out of 19 observed postures of the body members were classified as Action Category 2, which suggests they were slightly harmful to the musculoskeletal system and likely to cause discomfort. Of the so-called typical working postures, 31.9% was classified in Action Category 2, suggesting that during a substantial part of the working day typical working postures occur which are at least slightly harmful to the musculoskeletal system. Moreover, those work activities principally causing the workload to fall in OWAS' higher Action Categories were identified. For each of these three work activities an alternative work method was observed. The data show that in all three work activities the use of a vehicle lift reduces the number of poor working postures thereby reducing the load on the musculoskeletal system.

Accidents, Occupational

Simulation of nitrous oxide concentrations in operating and recovery rooms.

A model was developed to predict nitrous oxide (N2O) concentrations in operating (OR) and recovery rooms. The model incorporates general ventilation characteristics, percentage recirculation and the rate at which N2O is emitted into the OR (emission) for the calculation of environmental exposure. A workplace study was carried out during which N2O concentrations were measured continuously and coupled to anaesthetic activities (type and duration), air-change rate and percentage of recirculated air. The data from this study were used to calculate N2O emission. Subsequently, the model was used to predict the effect of technical measures to reduce emissions on mean environmental exposure. After implementation of the control measures an intervention study was made to check whether the reduction in exposure was predicted by our simulation model. Subsequently the 'validated' simulation model was used: (i) to calculate the exposure for different percentages of recirculation and different air-change rates, and (ii) to estimate N2O levels in another situation, i.e. an operating room in an outpatients clinic. In short, our study shows how modelling can help both occupational hygiene and hospital management to control exposure to anaesthetic gases and to design or adapt ventilation systems of operating rooms and recovery rooms.

Computer Simulation

Monitoring of nitrous oxide in operating rooms: identification of sources and estimation of occupational exposure.

In an academic hospital, nitrous oxide (N2O) levels were measured continuously and detailed workplace observations made in three different operating rooms for 18 days. The study was designed to determine the exposure of different categories of staff to nitrous oxide, to localize and quantify the emissions, and to predict and validate the effect of corrective measures. Nitrous oxide levels appeared to be highly time and place dependent; all staff, except for surgeons, were exposed to N2O levels (8-hour time-weighted average) above 25 parts per million. The most important contributor to total release of N2O was the ventilator (about 70%), especially during artificial respiration of the patient. A simulation model was developed and used to predict the effect of technical improvement of the ventilators and use of scavenging during anesthesia (total 58% reduction of release). The model shows that under these conditions, without altering room ventilation rates, room air circulation can be increased up to 50% without exceeding the proposed threshold limit value (25 parts per million). Measurement of N2O levels after intervention showed a reduction in the area surrounding the ventilator of about 80%, thereby reducing occupational exposure of all staff to below 18 parts per million.

Air Pollutants, Occupational

Blood anti-oxidant parameters at different stages of pneumoconiosis in coal workers.

The pneumoconioses are associated with chronic inflammatory processes during which increased amounts of reactive oxygen species are formed in the lower respiratory tract. To characterize the effect(s) of these processes on the defense system against free radicals, we studied 91 individuals with long-term occupational exposure to coal mine dust. Thirty-one subjects were classified with radiological evidence to be pneumoconiotics, while 58 control miners had no pulmonary disorders. We measured antioxidant parameters in red blood cells, considering the latter to reflect the oxidative stress in the lung. Glutathione levels were significantly decreased (p = 0.04) in red blood cells of miners with coal workers' pneumoconiosis with radiograph classification 0/1 to 2/1, while in miners with classification 3/2 to 3/3, the plasma iron concentrations were significantly decreased (p = 0.04). Moreover, some factors of the anti-oxidant system (superoxide dismutase, catalase, glutathione peroxidase) were correlated in the diseased but not in the control miners. Taken together, all data support the role of the erythrocyte as a circulating anti-oxidant carrier and also that changes in red blood cell anti-oxidant factors reflect the oxidative stress imposed by the pneumoconiotic (inflammatory) processes in the lung.

Adult

Epidemiologic studies of inorganic dust-related lung diseases in The Netherlands.

The results of two epidemiologic investigations on dust-related lung diseases are presented. The two studies had different aims and designs. A cross-sectional study was done to investigate the silicosis prevalence in Dutch fine ceramic workers. In the small ceramic workshops in the Gouda region, simple pneumoconiosis is still commonly present (13.3%), whereas the silicosis prevalence in the highly mechanized industries is low (1.7%). Furthermore, heavy smoking seems to enhance the risk for silicosis after long-term exposure to quartz. A case-control study was performed to analyze the relation between dust exposure in the fine ceramic and coal mining industries and lung cancer. No relation between a work history in the dusty trades and lung cancer emerged, and a correlation with a specific histologic tumor cell type could not be demonstrated. Apparently, workers in the Dutch fine ceramic or coal mining industry have no increased risk of developing lung malignancies.

Case-Control Studies

Molecular epidemiology of coal worker's pneumoconiosis: application to risk assessment of oxidant and monokine generation by mineral dusts.

It is generally accepted that fibrotic lung diseases are mediated by macrophage-derived cytokines and growth factors. Basic research continues to find new factors involved in these disease processes to incorporate into new hypotheses. Two hypotheses implicitly generated by recent findings were tested in an epidemiologic approach among workers in coal mines. This approach is described as molecular epidemiology and is exemplified by two studies focused on different mechanistic aspects of coal workers' pneumoconiosis (CWP): antioxidants in red blood cells of miners with CWP and generation of tumor necrosis factor (TNF) by blood monocytes of miners with CWP. Most findings in the antioxidant study may merely be reflections of pulmonary inflammatory processes. Some data in the TNF study indicate, however, that TNF release is a risk factor for the development of lung fibrosis after prolonged exposure to coal mine dust.

Adult

Increases in endogenous antioxidant enzymes during asbestos inhalation in rats.

Although the pathogenesis of asbestos-induced pulmonary damage is still not completely understood, an important role has been attributed to active oxygen species. In the present paper we present results of a study investigating the effect of crocidolite asbestos inhalation on different lung antioxidant enzymes in rats. During the development of pulmonary fibrosis induced by crocidolite asbestos, lung superoxide dismutase, catalase and selenium-dependent glutathione peroxidase activities increased, indicating an adaptive response to increased pulmonary oxidant stress. However, this adaptive response obviously is not sufficient to protect the lung from asbestos-induced pulmonary damage. Considering the role of active oxygen species in both the fibrotic process and tumor promotion, it is hypothesized that antioxidants may also protect the lung from chronic asbestos-induced pulmonary damage such as bronchogenic carcinoma.

Animals

In vitro effect of toluene diisocyanate on beta adrenergic and muscarinic receptor function in lung tissue of the rat.

To investigate the role of pharmacological mechanisms in toluene diisocyanate (TDI) induced occupational asthma, the effects of TDI on rat trachea ring and lung parenchymal strip were studied in vitro. The most prominent effect observed was a stimulation of metacholine (1 microM) induced contraction of the tracheal ring by 1 microM TDI (added in dimethy sulphoxide). The results were less pronounced when TDI was added from a stock solution prepared in water, which is possibly due to (co)polymerisation. It is concluded that the pharmacological effect of TDI may result from an autonomic imbalance between cholinergic and beta-adrenergic neural control.

Animals