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K Donaldson

Publications and source records attributed to K Donaldson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Free radical activity of synthetic vitreous fibers: iron chelation inhibits hydroxyl radical generation by refractory ceramic fiber.

Synthetic vitreous fibers are in widespread use but the parameters that dictate their carcinogenicity are still a matter of scientific debate. The free radical activities of a panel comprising an asbestos sample and five different respirable synthetic vitreous fiber samples were determined, to address the hypothesis that carcinogenic fibers have greater free radical activity than noncarcinogenic fibers. On the basis of recent inhalation studies, the six samples were divided into three carcinogenic fibers-amphibole asbestos, silicon carbide, and refractory ceramic fiber 1 (designated with the abbreviation RCF 1)-and three noncarcinogenic fibers--man-made vitreous fiber 10 (a glass fiber sample designated with the abbreviation MMVF 10), Code 100/475 glass fiber, and RCF4. All experiments were carried out with equal fiber numbers. Of the two assays of free radical activity used, the plasmid assay of DNA scission showed only amosite asbestos to have free radical activity, while the salicylate assay of hydroxyl activity showed that both amosite asbestos and RCF1 release hydroxyl radicals; silicon carbide fibers had no free radical activity in either of the assays. None of the noncarcinogenic fibers demonstrated free radical activity in either of the assays. The differences in the two assays in demonstrating free radical activity with RCF1 may be due to increased release of Fe from RCF1 under the more acid conditions of the salicylate assay, which was confirmed by the fact that soluble iron caused hydroxylation of salicylate. Presence of an iron chelator inhibited the ability of the RCF1 fibers to cause hydroxylation of salicylate, demonstrating that RCF1 generates hydroxyl radical by Fenton chemical reaction in the same way as amphibole asbestos.

Animals↗
PubMed1998

Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals.

Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rare. Additionally, ultrafine (uf) forms of these metals are used increasingly and there is little available information on their toxicity. Thus the inflammatory response following intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and sustained inflammation, cytotoxicity and increased epithelial permeability. The next most toxic material was DQ12 quartz, with Uf-Co being closely similar in ability to cause inflammation. Uf-TiO2 was more active than the saline control in all of the indices, but was the least toxic of the particles studied. The present study reveals that three ultrafine particles of the same diameter are dramatically different in their ability to cause inflammation. The three ultrafines were compared as to their ability to cause free-radical damage to supercoiled plasmid DNA, and the result of free-radical activity was found to be Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle types.

Animals↗
PubMed1998

Respirable fibres: surfactant coated fibres release more Fe3+ than native fibres at both pH 4.5 and 7.2.

Exposure to asbestos is associated with several lung diseases. The carcinogenic action of asbestos is not fully understood but oxidative stress is considered to play a role. Iron on the surface can lead to Fenton chemistry and the Haber Weiss reaction producing free radicals such as the hydroxyl radical, which is likely to be important. Little is known of the pathogenic action of man-made fibres. This study involved the use of a panel of man-made fibres, some of which were shown to be pathogenic and others shown to be non-pathogenic in recent animal studies. A short term assay measuring Fe3+ release from the fibres over a 20 hour time period, and also a longer study of 12 week, found that pathogenic and non-pathogenic fibres could not be differentiated according to Fe3+ release only. Iron release from native fibres was compared with that from surfactant-coated fibres, and in all cases surfactant coated fibres released more Fe3+ inferring that in vivo lung lining fluid coats native fibres and therefore affects the fibre surface chemistry and hence reactivity.

Animals↗
PubMed1998

The quartz hazard: a variable entity.

An IARC Working Group recently classified crystalline silica (quartz) into IARC's Group 1, i.e. a carcinogen. This classification is based on evidence of carcinogenicity in experimental animals and in humans. However, the evaluation stated that in making the overall evaluation, the Working Group noted that carcinogenicity to humans was not detected in all industrial circumstances studied and that carcinogenicity may be dependent on inherent characteristics of the crystalline silica or on external factors affecting its biological activity. The present review seeks to put the apparently conflicting findings of cancer incidence in quartz-exposed industries into a unifying thesis, based on mechanistic studies. These mechanistic studies have enabled the events leading from deposition of quartz to silicosis and cancer to be partially elucidated and have demonstrated that the biological effects of quartz can be understood in terms of surface reactivity. We particularly emphasise the ability of quartz to generate free radicals and cause oxidative stress and the fact that this could be modified by a range of substances that affect the quartz surface; some of these modifying substances could originate from other minerals. We therefore propose that the hazard posed by quartz is not a constant entity, but one that may vary dramatically depending on the origin of the silica sample or its contact with other chemicals/minerals within its complex constitution. The mechanistic data described here could assist in the interpretation of epidemiological studies and pose further hypotheses that could be tested in order to help resolve the quartz carcinogenesis anomaly. The data suggest that quartz cannot be death with as a single hazard entity, as is the case with most other chemicals.

Animals↗
PubMed1998

Constant temperature monitoring: a study of temperature patterns in the postanesthesia care unit.

Patients admitted to the PACU from the operating room exhibit fluctuations in core body temperature during the course of their stay in the PACU. Some patients present with normothermia and experience temperature decreases later in their stay. PACU policy does not dictate that temperatures be measured at a predetermined frequency in the absence of hypothermia; thus, it is possible that hypothermia may not be detected at its onset. The major purpose of this study was to describe the core body temperature patterns of postsurgical patients during the PACU stay. Secondary objectives were to (1) identify at which point in time patients become hypothermic and (2) describe length of stay in patients who develop hypothermia. Hypothermia was defined as a core tympanic temperature of less than 35.5 degrees C. A descriptive design was used using a convenience sample of 150 elective surgical patients over the age of 1 month who were normothermic on admission to the PACU. Data were analyzed using descriptive statistics. Concurrent tympanic and continuous axillary temperatures were monitored for comparison and trend monitoring. Temperatures showed clinically significant decreases into the hypothermic range (< 35.5 degrees C). Fifty-seven percent of the sample (n = 86) had temperatures that dropped after PACU admission and another 13% fell below 35.5 degrees C. Hypothermia occurred within the first 15 minutes of the PACU stay. The average length of stay for those that developed hypothermia was 1.83 hours. Monitoring temperatures more frequently will result in detecting hypothermia at its onset. Nurses may use the axillary device as a trend for continuous monitoring. Length of stay may be shortened if temperature management is embraced by the PACU nurse.

Adolescent↗
PubMed1998

Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells.

We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 microM), xanthine/xanthine oxidase (50 microM/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0. 008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O2) resulted in a time-dependent increase in GSH levels. gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 microM) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells.

Cell Line↗
PubMed1998

Lipopolysaccharide-induced alveolar epithelial permeability: the role of nitric oxide.

Intratracheal instillation of lipopolysaccharide (LPS) in the rat has been used as a model of acute lung inflammation. Among the early events in this process is a transient increase in airspace epithelial permeability which peaks 4 h after intratracheal instillation of LPS. The increased epithelial permeability is concomitant with the influx of neutrophils into the airspaces, peaking 8 h postinstillation. We have investigated the mechanism of this LPS-induced increase in epithelial permeability. The role of the neutrophil in LPS-induced epithelial permeability was assessed by pretreatment with neutrophil antibody to abolish neutrophil influx, which did not affect the increase in epithelial permeability. Because LPS instillation also induced increased tumor necrosis factor alpha (TNF-alpha) activity in bronchoalveolar lavage (BAL) fluid, and its release by cultured BAL leukocytes from treated animals, TNF-alpha antibody was coinstilled intratracheally with LPS in rats. TNF-alpha antibody eliminated TNF-alpha activity in BAL fluid, but had no effect on LPS-induced increased epithelial permeability. Increased levels of nitric oxide (NO), measured as nitrite, were also present in BAL fluid from LPS-treated rat lungs and LPS-elicited BAL leukocytes produced increased NO in culture. Treatment of rats with the specific NO synthase inhibitor L-NMMA significantly diminished the LPS-induced increased epithelial permeability. These data suggest that NO is involved in LPS-induced changes in epithelial integrity. However, other mechanisms should be evoked in addition to NO to explain completely the increased epithelial permeability produced by LPS.

Animals↗
PubMed1998

Hydrogen peroxide-induced epithelial injury: the protective role of intracellular nonprotein thiols (NPSH).

Injury to the alveolar region is a hallmark of the adult respiratory distress syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a characteristic of asthma. Reactive oxygen species have been implicated as mediators of lung injury in both of these conditions. We have investigated the relationship between intracellular nonprotein thiols (NPSH), and the release of the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury, following treatment of the human alveolar type II-like epithelial cell line (A549 cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen peroxide (H2O2). We have also assessed the protective effects of pre-incubation of both of these cells lines with H2O2 or enhancement of intracellular NPSH against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2 (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH in A549 cells, with a subsequent increase to above control values. 16HBE140- cells also showed a dose-dependent decrease in NPSH following exposure to H2O2. Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to H2O2 did not protect against H2O2-induced LDH release in this epithelial cell line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not intracellular reduced glutathione and resulted in total inhibition of H2O2-induced LDH release in both cell types. Pretreatment with reduced glutathione protected both cell types against the injurious effects of H2O2, whereas glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had no effect in 16HBE140- cells. Intracellular cysteine levels were increased in both cell lines following NAC exposure but not sufficiently to account for the increase in NPSH levels. These observations raise the possibility that a critical concentration of nonprotein thiols may be necessary to protect pulmonary epithelial cells against hydrogen peroxide-induced injury.

Acetylcysteine↗
PubMed1998

Introduction to the healing herbs.

For centuries, man has used plants for their healing properties. Today we refer to these plants as herbs. These plants play a principal part in all treatment modalities, both ancient and modern. The gentle, nourishing, and synergistic actions of herbal medicine make it an excellent treatment choice for all systems. Properties of ten commonly used herbs will be discussed. The herbs will be reviewed for their history, actions, indications and safety.

Humans↗
PubMed1997

Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins.

BACKGROUND: The fungus Aspergillus fumigatus, whose spores are present ubiquitously in the air, causes a range of diseases in the human lung. A small molecular weight (< 10 kD) heat stable toxin released from the spores of clinical and environmental isolates of A fumigatus within minutes of deposition in aqueous solution has previously been described. A key effect of the toxin was to inhibit the oxidative burst of macrophages as measured by superoxide anion release. It was hypothesised that the toxin was one of the commonly found A fumigatus hyphal toxins such as gliotoxin. This inhibitor may be an important factor which allows the fungus to colonise the lung. METHODS: The spore derived inhibitor was shown to inhibit the respiratory burst of rat alveolar macrophages, as measured by the generation of superoxide anion. Samples of the spore diffusate were subject to reversed phase high performance liquid chromatography (HPLC), thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), or organic extraction followed by TLC or HPLC to identify the presence of gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C. Commercially obtained preparations of the toxins gliotoxin, fumagillin and helvolic acid and extracts enriched for fumigaclavine-C and aurasperone-C were used as internal and external standards and in the respiratory burst measurements. RESULTS: Gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C were not detected in spore derived diffusate using PHLC or TLC. Using extraction procedures with solvents known to extract gliotoxin from A fumigatus culture supernatants, no gliotoxin was detected in the spore derived diffusate. Commercial gliotoxin, fumagillin, and helvolic acid or extracts enriched for fumigaclavine-C and aurasperone-C did not inhibit the oxidative burst of macrophages. CONCLUSIONS: The hypothesis that the spore derived toxin is one of the toxins derived from hyphae such as gliotoxin, helvolic acid, fumagillin, fumigaclavine-C, or aurasperone-C is not proved. The spore toxin may exert its effect through its ability to diffuse rapidly into the lung lining fluid, diminish the macrophage oxidative burst, and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects.

Animals↗
PubMed1997

Short-term inhalation and in vitro tests as predictors of fiber pathogenicity.

A wide range of fiber types was tested in two in vitro assays: toxicity to A549 epithelial cells, as detachment from substrate, and the production of the proinflammatory cytokine tumor necrosis factor (TNF) by rat alveolar macrophages. Three of the fibers were also studied in vivo, using short-term inhalation followed by a) bronchoalveolar lavage to assess the inflammatory response and b) measurement of cell proliferation in terminal bronchioles and alveolar ducts, using incorporation of bromodeoxyuridine (BrdU). The amount of TNF produced by macrophages in vitro depended on the fiber type, with the man-made vitreous fibers, and refractory ceramic fibers being least stimulatory and silicon carbide (SiC) whiskers providing the greatest stimulation. In the epithelial detachment assay there were dose-dependent differences in the toxicity of the various fibers, with long amosite being the most toxic. However, there was no clear relationship to known chronic pathogenicity. Fibers studied by short-term inhalation produced some inflammation, but there was no clear discrimination between the responses to code 100/475 glass fibers and the more pathogenic amosite and SiC. However, measurements of BrdU uptake into lung cells showed that amosite and SiC produced a greater reaction than code 100/475, which itself caused no more proliferation than that seen in untreated lungs. These results mirror the pathogenicity ranking of the fibers in long-term experiments. In conclusion, the only test to show potential as a predictive measure of pathogenicity was that of cell proliferation in lungs after brief inhalation exposure (BrdU assay). We believe that this assay should be validated with a wider range of fibers, doses, and time points.

Administration, Inhalation↗
PubMed1997

In vivo and in vitro proinflammatory effects of particulate air pollution (PM10).

Epidemiologic studies have reported associations between fine particulate air pollution, especially particles less than 10 mm in diameter (PM10), and the development of exacerbations of asthma and chronic obstructive pulmonary disease. However, the mechanism is unknown. We tested our hypothesis that PM10 induces oxidant stress, causing inflammation and injury to airway epithelium. We assessed the effects of intratracheal instillation of PM10 in rat lungs. The influx of inflammatory cells was measured in bronchoalveolar lavage (BAL). Airspace epithelial permeability was assessed as total protein in bronchoalveolar lavage fluid (BALF) in vivo. The oxidant properties of PM10 were determined by their ability to cause changes in reduced glutathione (GSH) and oxidized glutathione (GSSG). We also compared the effects of PM10 with those of fine (CB) and ultrafine (ufCB) carbon black particles. Six hours after intratracheal instillation of PM10, we noted an influx of neutrophils (up to 15% of total BAL cells) in the alveolar space, increased epithelial permeability, an increase in total protein in BALF from 0.39 +/- 0.01 to 0.62 +/- 0.01 mg/ml (mean +/- SEM) and increased lactate dehydrogenase concentrations in BALF. An even greater inflammatory response was observed after intratracheal instillation of ufCB, but not after CB instillation. PM10 had oxidant activity in vivo, as shown by decreased GSH in BALF (from 0.36 +/- 0.05 to 0.25 +/- 0.01 nmol/ml) after instillation. BAL leukocytes from rats treated with PM10 produced greater amounts of nitric oxide, measured as nitrite (control 3.07 +/- 0.33, treated 4.45 +/- 0.23 mM/1 x 10(6) cells) and tumor necrosis factor alpha (control 21.0 +/- 3.1, treated 179.2 +/- 29.4 unit/1 x 10(6) cells) in culture than BAL leukocytes obtained from control animals. These studies provide evidence that PM10 has free radical activity and causes lung inflammation and epithelial injury. These data support our hypothesis concerning the mechanism for the adverse effects of particulate air pollution on patients with airway diseases.

Air Pollutants↗
PubMed1997

Free radical activity of PM10: iron-mediated generation of hydroxyl radicals.

The purpose of this study was to test the hypothesis that particulate matter < or = 10 microns in aerodynamic diameter (PM10) particles have the ability to generate free radical activity at their surface. We collected PM10 filters from the Edinburgh, United Kingdom, Enhanced Urban Network sampling site, removed particles from the filter, and tested their ability to cause free radical damage to supercoiled plasmid DNA. We found that the PM10 particles did cause damage to the DNA that was mediated by hydroxyl radicals, as shown by inhibition of the injury with mannitol. The PM10-associated hydroxyl radical activity was confirmed using a high-performance liquid chromatography-based assay to measure the hydroxyl radical adduct of salicylic acid. Desferrioxamine abolished the hydroxyl radical-mediated injury, which suggests that iron was involved. Analysis of PM10 filters confirmed the presence of large amounts of iron and leaching studies confirmed that the PM10 samples could release substantial amounts of Fe(III) and lesser amounts of Fe(II). To investigate the size of the particles involved in the hydroxyl radical injury, we centrifuged the suspension of PM10 to clarity, tested the clear supernatant, and found that it had all of the suspension activity. We conclude, therefore, that the free radical activity is derived either from a fraction that is not centrifugeable on a bench centrifuge, or that the radical generating system is released into solution.

Air Pollutants↗
PubMed1997

Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors.

We studied asbestos, vitreous fiber (MMVF10), and refractory ceramic fiber (RCF1) from the Thermal Insulation Manufacturers' Association fiber repository regarding the following: free radical damage to plasmid DNA, iron release, ability to deplete glutathione (GSH), and activate redox-sensitive transcription factors in macrophages. Asbestos had much more free radical activity than any of the man-made vitreous fibers. More Fe3+ was released than Fe2+ and more of both was released at pH 4.5 than at pH 7.2. Release of iron from the different fibers was generally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stress, as revealed by depletion of intracellular GSH. Amosite asbestos upregulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the only fiber to enhance activation of the transcription factor nuclear factor kappa B (NF kappa B). The use of cysteine methyl ester and buthionine sulfoximine to modulate GSH suggested that GSH homeostasis was important in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of transcription factor activation and therefore gene expression in alveolar macrophages. Although this was not related to iron release or ability to deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.

Animals↗
PubMed1997

Monocyte analysis in chronic myelomonocytic leukaemia.

It is suggested that monocytes in patients with chronic myelomonocytic leukaemia (CMML) or chronic myeloid leukaemia (CML) with monocytosis have morphological/functional abnormalities which cause inaccurate counting in automated analysers. In this study, monocytes in 21 normal and 14 CMML blood samples were subjected to morphological analysis and were counted by the manual reference method, three automated analysers and esterase staining. Morphological analysis showed no significant difference between control and CMML monocytes. The alpha-naphthyl acetate esterase scores, a measure of monocyte function, showed a reduction of 40% in CMML monocytes compared to controls. Counts by analysers showed that the Sysmex NE 8000 was the least accurate for CMML monocyte counts and that the Coulter STK-S and Sysmex SE 9000 gave results closer to the manually counted standards.

Humans↗
PubMed1996

Energy expenditure and symptom severity in men with heart failure.

Our results demonstrate a graded increase in resting metabolic rate based on symptom severity as reflected in the New York Heart Association classification. This finding supports the hypothesis that clinical severity of illness corresponds to the magnitude of the increase in resting energy demands.

Aged↗
PubMed1996

When is hypospadias not hypospadias?

Hypospadias is a deformity of urethral and penile development in the male. Some cases are secondary to more serious disorders of sexual differentiation. Simple clinical rules can sort the common morphological defect of hypospadias from the rarer but more dangerous diagnosis of intersex.

Disorders of Sex Development↗