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Biomedical subjects

R Slade

Publications and source records attributed to R Slade.

At least 19 recordsLinked to original sources
PubMed1997

Mouse strain differences in ozone dosimetry and body temperature changes.

Strain differences in susceptibility to inhaled ozone (O3) have been observed in mice, with C57BL/6J (B6) mice reported to be more sensitive than C3H/HEJ (C3) mice when exposed to equal concentrations of O3. To determine whether differences in the delivered dose of O3 to the lung could help explain these differences, C3 and B6 mice were exposed to 18O-labeled ozone (18O3), and the resulting 18O concentrations in pulmonary tissues were monitored as an indicator of O3 delivered dose. Body core temperatures (Tco) of similarly treated mice were measured during O3 exposures (using surgically implanted temperature probes) in an effort to correlate lung O3 dose to changes in basal metabolism. Immediately after exposure to 18O3, C3 mice had 46% less 18O (per mg dry wt) in lungs and 61% less in tracheas than B6 mice. Nasal 18O tended to be lower in the C3 mice, but these differences were not significant. Although both strains responded to the O3 exposure with significant decreases in Tco, C3 mice had a 70% greater mean temperature x time product decrease during the exposure than B6 mice. These results suggest that the strain differences in O3 susceptibility may be due to differences in O3 dose to the lung, which may be related to differences in the ability of the mice to lower their Tco in response to O3 exposure.

Animals↗
PubMed1997

Dietary restriction mitigates ozone-induced lung inflammation in rats: a role for endogenous antioxidants.

Studies were undertaken to determine whether dietary restriction protects against acute pulmonary oxidant challenge. Male F344 rats were fed NIH-31 diet either ad libitum or at restricted levels equal to 75% that of ad libitum intake. After 3 wk of dietary adaptation, animals were exposed by inhalation to 2.0 ppm ozone (O3) for 2 h or chamber air and evaluated for cellular and biochemical indices of pulmonary toxicity. Compared to air controls, bronchoalveolar lavage fluid (BALF) from O3 exposed ad libitum fed rats contained increased protein (145 versus 380 microg/ml), PMN infiltration (0 versus 11%) and fibronectin (45 versus 607 U/ml). Diet restriction abrogated these indicators of pulmonary inflammation induced by ozone. Binding of 18O3 to BALF protein and cells was significantly decreased in diet restricted rats while BALF ascorbate and glutathione levels, but not alpha-tocopherol or urate, were elevated compared to ad libitum fed rats. Taken together, these results indicate that dietary restriction affords protection against O3-induced oxidant toxicity. Protection is mediated partially by increases in ascorbate in the fluid bathing the lung surface, thereby providing an antioxidant sink which minimizes the ability of O3 to reach biological targets.

Animals↗
PubMed1996

Ozone toxicity in the mouse: comparison and modeling of responses in susceptible and resistant strains.

Previous studies from this laboratory have demonstrated a concentration-related hypothermia and increases in bronchoalveolar lavage (BAL) fluid indexes of toxicity in the rat after exposure to environmentally relevant levels of ozone (O3). In similar studies with C57BL/6J (B6) and C3H/HeJ (C3) mice, other investigators have reported differential effects on BAL toxicity indexes between the two strains after O3 exposure. The present study investigated the relationship between the reported strain differences in BAL parameters in B6 and C3 mice exposed to O3 and the induced hypothermic response. Male 80-day-old mice (n = 94, 47/strain) were used for these studies. Subsets (n = 8/strain) of these animals were surgically implanted with radiotelemetry transmitters that permitted continuous monitoring of core body temperature and activity. All telemetry animals and an equal number of nontelemetry animals (n = 8/strain) were exposed to filtered air for 24 h followed by a 2-h exposure to 2 parts/million 16O3. With use of a similar protocol, groups of nontelemetry mice (n = 12/strain) were exposed to either filtered air or 2 parts/million 16O3 for 2 h. At 0 or 22 h postexposure, mice were anesthetized with halothane and intubated, and their lungs were lavaged with 37 degrees C saline. Although both strains of mice exhibited significant abrupt decreases in core body temperature on exposure to O3 and both recovered rapidly after cessation of the O3 exposure, the response of the C3 mice was more dynamic than that of the B6 mice. Similarly, both strains showed characteristic changes in biomarkers of O3 toxicity; however, the increases in BAL fluid protein and cells at 22 h postexposure were significantly greater and the percentage of neutrophils was significantly less in B6 mice than in C3 mice. It is possible that the strain differences in BAL constituents may be related to the differences in the hypothermic response.

Animals↗
PubMed1994

Ozone dose and effect in humans and rats. A comparison using oxygen-18 labeling and bronchoalveolar lavage.

In an effort to improve risk assessments for ozone (O3) we compared the incorporation of inhaled oxygen-18-labeled O3 (18O3) into the lungs of humans and laboratory rats. Cells and fluids obtainable through bronchoalveolar lavage (BAL) were examined after exposure to 18O3 to determine whether excess 18O concentrations (presumed to be reaction products of 18O3) could be detected and equated to the O3 dose to the lung. Three O3 effect measurements (increased BAL protein and neutrophils and decreased BAL macrophages) were also made in subjects or animals exposed in parallel to determine whether there was a correspondence between dose and effect measurements. Eight human male volunteers 18 to 35 yr of age were exposed to 18O3 (0.4 ppm for 2 h) with 15-min alternating periods of heavy treadmill exercise and rest. Rats (F344) were exposed identically, except without exercise. 18O3 was generated directly from pure 18O2. BAL cells and centrifugally separable surfactant material were freeze-dried and analyzed by mass spectrometer for excess 18O. Results showed that the exercising humans had four- to fivefold higher 18O concentrations in all of their BAL constituents than did the rats. The humans also had significant increases in all of the effects markers after 0.4 ppm O3, whereas the rats did not. Rats that were exposed to higher concentrations of 18O3 (2.0 ppm) had levels of 18O in BAL that were more comparable to but still lower than those of exercising humans. Changes in all of the effects markers in these rats were comparable or higher than in exercising humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Application of the EPR spin-trapping technique to the detection of radicals produced in vivo during inhalation exposure of rats to ozone.

Ozone is known to induce lipid peroxidation of lung tissue, although no direct evidence of free radical formation has been reported. We have used the electron paramagnetic resonance (EPR) spin-trapping technique to search for free radicals produced in vivo by ozone exposure. The spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was administered ip to male Sprague-Dawley rats. The rats were then exposed for 2 hr to either 0, 0.5, 1.0, 1.5, or 2.0 ppm ozone with 8% CO2 to increase their respiratory rate. A six-line 4-POBN/radical spin adduct signal (aN = 15.02 G and a beta H = 3.27 G) was detected by EPR spectroscopy in lipid extracts from lungs of rats treated with 4-POBN and then exposed to ozone. Only a weak signal was observed in the corresponding solution from rats exposed to 0 ppm ozone (air with CO2 only). The concentration of the radical adduct increased as a function of ozone concentration. After administration of 4-POBN, rats were exposed for either 0.5, 1.0, 2.0, or 4.0 hr to either 0 or 2.0 ppm ozone (with CO2). The radical adduct concentration of the ozone-exposed groups at exposure times of 2.0 and 4.0 hr was significantly different from that of the corresponding air control groups. A correlation was observed between the radical adduct concentration and the lung weight/body weight ratio. These results demonstrate that ozone induces the production of free radicals in rat lungs during inhalation exposure and that radical production may be involved in the induction of pulmonary toxicity by ozone. This is the first direct evidence for ozone-induced free radical production in vivo.

Administration, Inhalation↗
PubMed1991

Towards the selection of cattle for tick resistance in Africa.

Half-body tick collections and visual assessment of tick burdens were performed monthly over six months on 100 bulls at the Kenya National Boran Stud, Mutara Ranch, Kenya. Boophilus decoloratus predominated among several tick species infesting the animals. Burdens of B. decoloratus and total tick burdens were highly correlated. Rankings of relative tick resistance among bulls were consistent from month to month. Rankings based on visual assessment were very close to those based on actual tick burdens. Animals with thin skins appeared to carry fewer ticks, but tick burden bore no relationship to coat colour. The results suggest that simple visual inspection of total tick burdens may be a suitable basis for the selection of tick resistance in cattle.

Animals↗
PubMed1990

Gastrointestinal malignancies as a complication of chronic myeloid leukaemia.

A 70-year-old patient is presented who, after chemotherapy for chronic myeloid leukaemia, developed two separate gastrointestinal malignancies. His family history indicated a strong family tendency towards neoplasia, and it is speculated that this predisposition may have been potentiated by the chemotherapy or the leukaemic process itself. It is stressed that, in such cases of multiple malignancy, each condition should be treated on its own merits.

Adenocarcinoma↗
PubMed1989

Incorporation and disappearance of oxygen-18 in lung from mice exposed to 1 ppm 18O3.

In this study, 18O3 was used as a tracer for inhaled ozone in mice. The amount of ozone-derived oxygen (ODO) in the lungs was determined by measuring the amount of oxygen-18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung following exposure to 1 ppm 18O3 for less than or equal to 60 min. The rate of disappearance of ODO from the lungs was determined by quantifying the rate of decrease of oxygen-18 in excess of the natural abundance level in lung from mice exposed to 1 ppm 18O3 for 45 min. With exposure to 1 ppm 18O3. ODO accumulated in lung at a rate of 4.38 pmol/mg dry weight/min. Ozone-derived oxygen had a half-life in lung of approximately 6 hr. We estimate that a minimum of 44 pmol of O3 reacted with lung every minute of exposure to 1 ppm O3.

Animals↗
PubMed1989

Agranulocytosis caused by dapsone therapy for granuloma annulare.

Dapsone has been suggested as a useful drug in the treatment of granuloma annulare; however, adverse reactions include a potentially life-threatening agranulocytosis. We report the case of a 50-year-old woman in whom agranulocytosis and septicemia developed after 7 weeks of therapy with dapsone for granuloma annulare. Full recovery followed cessation of this drug, but caution is advised in prescribing dapsone for relatively benign skin conditions.

Agranulocytosis↗
PubMed1988

Detection of CCl4-induced oxidation of hepatic tissue in vivo by oxygen-18 tracing.

Oxidation of rat hepatic tissue was measured as incorporation of oxygen-18 (18O) from 18O2 following exposure to carbon tetrachloride (CCl4). Anesthetized rats were injected with CCl4 and allowed to breathe 18O2 for 1 hr, and then livers were homogenized, fractionated, and dried. The dried fractions were pyrolyzed to CO by an oxygen elemental analyzer, the CO was oxidized to CO2, and isotope ratio mass spectrometry was used to determine the abundance of 18O in the CO2. Rats that breathed 18O2 (21% in N2) for 1 hr had significant incorporation of 18O into lipids, solutes, and macromolecules of the liver. Injection with CCl4 increased incorporation of 18O into all liver fractions, although this increase was significant only in the lipid fraction. Rats pretreated with phenobarbital and then given CCl4 had significantly increased 18O in all liver fractions although it was greatest in the lipid fraction. About 5 mumol of 18O per gram of dry liver was incorporated in phenobarbital/CCl4-treated rats, of which 60% was in the water-soluble fraction, 17% in the lipids, and 16% in the macromolecules. Piperonyl butoxide administration abolished the CCl4-induced 18O incorporation. Thus, 18O incorporation appeared to provide a measure of oxidation in all tissue fractions following in vivo CCl4-induced liver injury.

Animals↗
PubMed1986

Nitrogen dioxide exposure and lung antioxidants in ascorbic acid-deficient guinea pigs.

We have previously found that ascorbic acid (AA) deficiency in guinea pigs enhances the pulmonary toxicity of nitrogen dioxide (NO2). The present study showed that exposure to NO2 (4.8 ppm, 3 hr) significantly increased lung lavage fluid protein (a sensitive indicator of pulmonary edema) only in guinea pigs fed rabbit chow (a diet not supplemented with vitamin C) for at least 7 days, at which time lung AA was about 50% of normal. The rabbit chow diet did not cause reduced body weight as did commercial synthetic scorbutic diets, even when they were supplemented with AA. After 14 days of feeding rabbit chow, lung AA was reduced to 15% of control. At this time, alpha-tocopherol (AT) in the same lungs was reduced to 85% of control, and lung nonprotein sulfhydryls (NPSH) were increased to 114% of control. Exposure of the guinea pigs to NO2 (4.5 ppm, 16 hr) increased wet lung weight and further altered the antioxidants in deficient (but not normally fed) animals in the following manner: NPSH content was increased to 130% of control, AT was decreased to 74% of control, and AA was increased from 15 to 50% of control. These findings suggest that depletion of AA in guinea pigs removes an important defense against NO2. The lung appears to be able to partially compensate for the dietary lack of antioxidant by accumulating AA from other tissues and by increasing NPSH concentrations. However, sufficient exposure to NO2 leads to oxidation of AT and pulmonary edema. Conditions in which NO2 produced edema were accompanied by only a slight consumption of AT, and no detectable oxidation of lung AA or NPSH.

Animal Feed↗
PubMed1986

Species comparison of acute inhalation toxicity of ozone and phosgene.

A comparison of the concentration-response effects of inhaled ozone (O3) and phosgene (COCl2) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl2 and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl2-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm O3 and above, while rabbits responded only at 2.0 ppm O3. Phosgene similarly affected mice, hamsters, and rats at 0.2 ppm and above, while guinea pigs and rabbits were affected at 0.5 ppm and above. Percent recovery of lavage fluid varied significantly between species, guinea pigs having lower recovery than other species with both gases. Lavage fluid recovery was lower following exposure to higher levels of O3 but not COCl2. Results of this study indicate that significant species differences are seen in the response to low levels of O3 and COCl2. These differences do not appear to be related in a simple manner to body weight.

Animals↗
PubMed1985

Comparison of lung antioxidant levels in humans and laboratory animals.

Basal lung concentrations of ascorbic acid (AA), nonprotein sulfhydryls (NPSH), and alpha-tocopherol (alpha-T) were determined in rabbits, guinea pigs, rats, hamsters, mice, domestic pigs and sheep, and in human lung samples obtained from cancer surgery patients. Significant differences were found among the laboratory animals: AA levels ranged from 25.6 mg% (mg/100 g wet weight) in hamsters to 41.7 mg% in mice, NPSH from 50.9 mg% in rats to 84.7 mg% in rabbits, and alpha-T from 1.01 mg% in hamsters to 2.74 mg% in rats. Porcine lung AA and NPSH concentrations approximated those of the laboratory animals and their alpha-T levels were the highest of all species studied. Sheep lung AA levels were comparable to those in the other species, although their NPSH and alpha-T levels appeared to be lower. Human lung concentrations of NPSH (5.2 mg%) and alpha-T (0.85 mg%) appeared low, whereas the mean AA concentration (22.1 mg%) was similar to that of laboratory animals. A partial correlation was found between AA and alpha-T levels and between NPSH and alpha-T levels in the 5 laboratory animal species.

Adult↗
PubMed1984

Glomerulonephritis, non-Hodgkin's lymphoma and leucocytoclastic vasculitis.

2 cases of active focal proliferative glomerulonephritis, lymphocytic malignant lymphoma and leucocytoclastic vasculitis are described. 1 presented with the nephrotic syndrome and progressive renal impairment, the other with acute renal failure. Cryoglobulins were detected in the serum of 1 patient, but not in that of the other. Initial renal and skin biopsies in the 2 patients were strikingly similar. As well as demonstrating glomerular lesions, the renal biopsies contained interstitial lymphomatous infiltrate which, in 1 case, was initially incorrectly interpreted and resulted in delay in specific treatment. Immunosuppressive therapy markedly improved renal function and induced remission of the vasculitis and lymphoma. Repeat renal biopsy in 1 case confirmed regression of the glomerulonephritis. A common immunological aetiology may explain the co-existence of these three conditions in the 2 patients.

Biopsy↗