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Biomedical subjects

K Donaldson

Publications and source records attributed to K Donaldson.

189 records · Page 11Linked to original sources
PubMed1980

The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats.

Four groups of rats were treated by inhalation with the UICC preparations of amosite or chrysotile in order to explore the effects of intermittent high dust concentrations (peak dosing). For each of the 2 asbestos types one group of rats was treated for 5 days each week, 7 h a day, for 1 year. Two other groups were treated with amosite or chrysotile at 5 times the previous dose for 1 day each week for 1 year. Results showed that the lung dust levels of both chrysotile or amosite in the lungs of rats after the 12-month inhalation period were similar regardless of whether "peak" or "even" dosing had been used. During the following 6 months, asbestos was cleared from the "peak" chrysotile group more slowly than the "even" chrysotile group but clearance from the "peak" amosite group was faster than that found after "even" dosing with amosite. Levels of early peribronchial fibrosis were generally lower for the "peak" dosing groups than for "even" dosing although levels of interstitial fibrosis were slightly higher following "peak" dosing. The incidence of pulmonary neoplasms did not differ between the "peak"-dosing and "even"-dosing experiments. These findings therefore give no indication that short periods of high dust exposure in an asbestos factory would result in a significantly greater hazard than would be indicated by the raised overall dust counts for the day in question.

Animals↗
PubMedDate not supplied

Comparative aspects of plasma antioxidant status in sheep and goats, and the influence of experimental abomasal nematode infection.

This paper provides, for the first time, comparative data on the plasma antioxidant status of two ruminant species, namely sheep and goats. In addition, the influence of experimental infection with Teladorsagia circumcincta on antioxidant status in the same two species is compared and contrasted. In general terms, antioxidant status was significantly higher in uninfected kids than in lambs. Differences in protein sulphydryl groups and vitamin E concentrations were particularly noteworthy; trends were similar, however, for albumin, vitamin A and total antioxidant capacity (TAC). Parasitological results, based on worm burden, faecal egg counts and peripheral blood eosinophil numbers, confirmed that goat kids were more susceptible than lambs to experimental T. circumcincta infection. "Trickle infection" had a variable impact on both total and individual antioxidant status; particularly during the early weeks, the trend was for reduced values in lambs and increased values in kids, as compared with uninfected controls. Subsequent challenge infection was associated with a transient decrease in TAC and albumin in trickle-infected animals of both species, and in appropriate control animals. The observed differences in plasma antioxidant capacity between sheep and goats may have important implications in terms of the comparative resilience of sheep and goats to parasite infection.

Abomasum↗
PubMedDate not supplied

Nonneoplastic lung responses induced in experimental animals by exposure to poorly soluble nonfibrous particles.

The intent of this article is to review the comparative nonneoplastic pathological responses (inflammation, fibrosis, and epithelial proliferation) of rats, hamsters, mice, and monkeys to low-toxicity dusts (TiO(2), carbon black, talc, coal-mine dust, and diesel particulate). The paucity of information on some of these comparisons and the important information on other dusts (e.g., silica) that illuminate this question have necessitated inclusion of a number of papers that go beyond these nontoxic dusts.

Air Pollutants↗
PubMedDate not supplied

Mechanistically identified suitable biomarkers of exposure, effect, and susceptibility for silicosis and coal-worker's pneumoconiosis: a comprehensive review.

Clinical detection of silicosis is currently dependent on radiological and lung function abnormalities, both late manifestations of disease. Markers of prediction and early detection of pneumoconiosis are imperative for the implementation of timely intervention strategies. Understanding the underlying mechanisms of the etiology of coal workers pneumoconiosis (CWP) and silicosis was essential in proposing numerous biomarkers that have been evaluated to assess effects following exposure to crystalline silica and/or coal mine dust. Human validation studies have substantiated some of these proposed biomarkers and argued in favor of their use as biomarkers for crystalline silica- and CWP-induced pneumoconiosis. A number of "ideal" biological markers of effect were identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor-alpha (TNF-alpha) (monocyte release), interleukin-8 (IL-8) (monocyte release), reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil release), 8-isoprostanes (serum), total antioxidant levels measured by total equivalent antioxidant capacity (TEAC), glutathione, glutathione peroxidase activity, glutathione S-transferase activity, and platelet-derived growth factor (PDGF) (serum). TNF-alpha polymorphism (blood cellular DNA) was identified as a biomarker of susceptibility. Further studies are planned to test the validity and feasibility of these biomarkers to detect either high exposure to crystalline silica and early silicosis or susceptibility to silicosis in gold miners in South Africa.

Air Pollutants, Occupational↗
PubMedDate not supplied

Reduction of the proteolytic activity of neutrophils by exposure to cigarette smoke in vitro.

Human peripheral blood neutrophils were exposed in vitro, in a tonometer, to two different fractions of cigarette smoke-designated particulate phase and vapor phase. The proteolytic activity of the cells following exposure was assessed by measuring their elastase release and ability to degrade fibronectin. At levels of smoke exposure that were physiologically attainable, neither smoke fraction caused an increase in elastase release or fibronectin degradation. In most experiments, fibronectin proteolysis was suppressed by smoke exposure--an effect that was reversible on treatment with phorbol myristate acetate. These data provide evidence that the proteolytic activity of neutrophils is not enhanced by a direct effect of cigarette smoke on these cells.

Carboxyhemoglobin↗
PubMedDate not supplied

Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro.

Tumor necrosis factor (TNF) is a cytokine released predominantly by monocytes/macrophages that has been shown to modulate a variety of different immune and metabolic functions. To understand the regulatory mechanisms of TNF in governing responses in the pleural cavity following deposition of fibrous dust in the airspace of the lung, we studied the capability of leukocytes, lavaged from the pleural cavity, to release TNF in culture. TNF production by lavaged pleural leukocytes was measured using the L-929 TNF-sensitive cell line, after intratracheal instillation of crocidolite asbestos. A high level of TNF activity was found in the supernatants of normal, unstimulated pleural leukocytes; the addition of 100 ng/ml lipopolysaccharide to the culture increased the activity up to threefold. Following intratracheal instillation of 5 mg crocidolite asbestos, the pleural leukocytes secreted less TNF than the control. With increasing mass of intratracheally instilled asbestos, there was a dose-dependent reduction in TNF release. Changes in the population of the pleural leukocytes or their number could not be related to variation in TNF activity. These results suggest that exposure of rat lungs to crocidolite asbestos by intratracheal instillation affects the response of pleural leukocytes without causing changes in the population. Such changes in the bronchoalveolar space may be related to the pleural pathology found in asbestos-exposed individuals.

Animals↗
PubMedDate not supplied

Enhancement of the macrophage oxidative burst by immunoglobulin coating of respirable fibers: fiber-specific differences between asbestos and man-made fibers.

The ability of long amosite asbestos fibers (LFA), vitreous fibers (MMVF 21 and CODE 100/475), and ceramic fibers (silicon carbide and RCF 1) to stimulate superoxide production in isolated rat alveolar macrophages is examined. The cells were exposed to both naked fibers (uncoated) and fibers coated with rat immunoglobulin (IgG), a normal component of lung lining fluid. The affinity for IgG of the various fibers was assessed by quantifying the binding of 125I-labeled IgG onto the fiber surface. Naked fibers stimulated a modest release of superoxide anion from alveolar macrophages, which was not obviously dose dependent. When IgG was adsorbed onto fibers of MMVF 21 and RCF 1, there was a dramatic increase in superoxide release, which correlated well with their high affinity for IgG.IgG-adsorbed code 100/475 and silicon carbide whiskers (SiCW) stimulated only modest superoxide release, and the fibers showed a correspondingly poor affinity for the opsonin. Conversely, the adsorbed fibers of LFA, generated a dramatic increase in superoxide release from the macrophages, despite a relatively poor adsorption of IgG. This study demonstrates the potential for components of the lung lining fluid to modify the response of alveolar macrophages to respirable natural and man-made fibers. It also draws attention to fiber-specific differences in adsorptive capacity and subsequent biological activity between these fiber types in vitro and, by implication, in vivo.

Animals↗