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Biomedical subjects

C E Cross

Publications and source records attributed to C E Cross.

At least 19 recordsLinked to original sources
PubMed1992

Interaction of nitrogen dioxide with human plasma. Antioxidant depletion and oxidative damage.

Nitrogen dioxide (NO2.) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO2. caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of alpha-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation, alpha-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of alpha-tocopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and alpha-tocopherol may be important agents protecting against NO2. in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO2..

Adult↗
PubMed1992

Superoxide formed from cigarette smoke impairs polymorphonuclear leukocyte active oxygen generation activity.

Reactive free radicals contained in cigarette smoke (CS) and compromised phagocytic antimicrobial activities including those of polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of severe CS-related pulmonary disorders. In CS-exposed buffer solutions, O2-. was the predominant generated reactive oxygen species, as demonstrated by lucigenin-amplified chemiluminescence and electron spin resonance (ESR) spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). When PMNs were incubated in this buffer, phorbol 12-myristate 13-acetate (PMA)-stimulated active oxygen production and coupled O2 consumption were strongly impaired without appreciably affecting PMN viability (1-min exposure inhibited active oxygen production by 75%). Superoxide dismutase (SOD) totally protected and an iron chelator, diethylenetriaminepentaacetic acid (DETAPAC), also protected the CS-exposed PMNs, suggesting that generated O2-. was an initiating factor in the impairment and OH. generation was a subsequent injurious factor. Pretreatment of PMNs with antioxidants such as alpha-tocopherol and dihydrolipoic acid (DHLA) was partially protective. The results suggest that (i) O2-. is probably generated in the upper and lower respiratory tract lining fluid when they come in contact with CS; (ii) such generated O2-. can primarily impair PMN capabilities to generate reactive oxygen species; and (iii) since these effects may contribute to the pathogenesis of CS-related lung diseases, prior supplementation with antioxidants such as alpha-tocopherol or DHLA might be successful in preventing these deleterious effects.

Animals↗
PubMed1992

Modification of plasma proteins by cigarette smoke as measured by protein carbonyl formation.

Exposure of human plasma to gas-phase (but not to whole) cigarette smoke (CS) produces oxidative damage to lipids [Frei, Forte, Ames & Cross (1991) Biochem. J. 277, 133-138], which is prevented by ascorbic acid. The ability of CS to induce protein damage was measured by the carbonyl assay and by loss of enzyme activity and protein -SH groups. Both whole and gas-phase CS caused formation of carbonyls in human plasma, which was partially inhibited by GSH but not by ascorbic acid or metal-ion-chelating agents. Isolated albumin exposed to CS showed much faster carbonyl formation (per unit protein) than did whole plasma; damage to isolated albumin was partially prevented by chelating agents. Isolated creatine kinase (CK) lost activity upon exposure to CS much faster than did CK in plasma. Direct addition to plasma of mixtures of some or all of the aldehydes reported to be present in CS caused protein carbonyl formation and inactivation of CK, but neither occurred to the extent produced by CS exposure.

Adult↗
PubMed1992

Oxidative damage to plasma constituents by ozone.

The reaction of ozone (O3) with human blood plasma was studied to help understand possible events that could occur in the respiratory tract. Uric acid (quantitatively the most important scavenger) and ascorbic acid were oxidized quickly, protein-SH groups were lost more slowly, and there was no loss of bilirubin or alpha-tocopherol. There was little formation of lipid hydroperoxides and no detectable formation of 4-hydroxynoneal, hexanal or nonanal, or changes in lipoprotein electrophoretic mobility. Uric acid in human upper airway secretions may play a significant role in removing inhaled O3. Oxidative damage to lipids must not be assumed to be the key mechanism of respiratory tract O3 toxicity.

Adult↗
PubMed1992

Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow.

Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs.

Analysis of Variance↗
PubMed1992

Oxidative damage to human plasma proteins by ozone.

Exposure of human plasma to ozone produces oxidative protein damage, measured as protein carbonyl formation. Isolated human albumin or creatine phosphokinase are oxidized much faster than are total proteins. Consideration must be given to proteins as targets of oxidative injury by ozone in vivo.

Adult↗
PubMed1991

Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid.

Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low-density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins.

Adult↗
PubMed1991

Laser Doppler velocimetry of tracheal blood flow in sheep.

A laser-Doppler velocimetry (LDV) apparatus was adapted to assess sheep airway blood flow. The LDV signal obtained was compared to microsphere determinations of blood flow to tracheal tissues utilizing 15 microns radioactive microspheres injected before and after intubation and anesthesia, during hemorrhagic hypotension, and after reinfusion-resuscitation. During hemorrhagic hypotension, airway wall blood flow decreased to 16% of control by the microsphere method and to 30% by LDV. After reinfusion-resuscitation, airway wall blood flow increased over control values 40% and 33% by the two methods, respectively. Although at low flows LDV values were greater than microsphere determinations, the overall LDV recordings correlated with airway microsphere flow determinations of tracheal wall blood flow (R = 0.85) and tracheal mucosa flow (R = 0.81), but not with tracheal muscularis flow (R = 0.32). With certain but significant limitations, such as calibration in absolute units, stability of position placement, motion artifacts, and the effects of mechanical irritation-induced hyperemia, LDV represents a relatively noninvasive means for qualitatively evaluating changes in the microcirculatory blood flow of airway mucosa.

Animals↗
PubMed1991

Cytologic, microbiologic, and biochemical analysis of bronchoalveolar lavage fluid obtained from 24 healthy cats.

Twenty-four healthy cats underwent bronchoscopy and bronchoalveolar lavage to determine the normal cytologic environment of the lower respiratory tract of cats. Initial screening to ensure the health of the study population included complete histories, physical examinations, thoracic radiography, CBC, serologic tests for feline leukemia virus, feline immunodeficiency virus, and occult heartworm, and sugar and Baermann fecal flotation. In 18 cats, protected catheter brush samples of airway secretions from the lavaged lung segment were taken for culture of aerobic and anaerobic bacteria and mycoplasma. Bronchial lavage fluid (5 sequential 10-ml aliquots of normal saline solution) was pooled and filtered with cotton gauze. The unspun sample was used for determination of a total nucleated cell count. Lavage fluid was cytocentrifuged and 500 cells/slide were scored for determination of the cellular differential. Activity of lactate dehydrogenase and concentrations of total protein and IgG within the supernatant were measured, and assays were performed to detect the presence of IgA and IgM. Complete histologic evaluation of the lavaged lung of each of 6 random-source cats was performed after differential cell counting revealed 18% eosinophils within bronchoalveolar lavage fluid recovered from this group. Alveolar macrophages were the predominant cells encountered; however, a quarter of all cells recovered were eosinophils. A significant relationship was not found between the abundance of eosinophils in the lavage fluid, and either isolation of aerobic bacteria, high total nucleated cell counts, total protein concentrations, or activity of lactate dehydrogenase. Histologic evaluation of the lungs of 5 of 6 random-source cats revealed normal lungs in 2 cats, and minimal abnormal change in 3 others. Evaluation of the lungs from 1 random source cat revealed acute, mild eosinophilic bronchiolitis. We conclude that large numbers of eosinophils may be retrieved from the bronchoalveolar lavage fluid of healthy cats.

Animals↗
PubMed1990

Acute ozone exposure increases bronchial blood flow in conscious sheep.

This study was initiated to determine the effects of ozone (O3) on sheep airway blood flow. Twenty-three nasally intubated sheep were exposed to filtered air (n = 5), 1 ppm O3 (n = 4), 2 ppm O3 (n = 5), 3 ppm O3 (n = 5), and 4 ppm O3 (n = 4) for 3 h. Bronchial artery flow (Qbr) was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored during the period of the exposures. Exposure to 3 and 4 ppm O3 resulted in a significant increase in Qbr (103 and 204% change, respectively) without affecting any of the other cardiopulmonary parameters measured. These results indicate that O3 induces a dose dependent increase in Qbr which is the result of a vasodilation of the bronchial vasculature which is not dependent upon changes in blood gases or upstream driving pressure.

Administration, Intranasal↗
PubMed1990

Expression of mucin synthesis and secretion in human tracheobronchial epithelial cells grown in culture.

The effects of culture conditions on growth and differentiation of human tracheobronchial epithelial (HTBE) cells have been defined. Epithelial cells were dissociated from tissues by protease treatment and were plated on tissue culture dishes in F12 medium supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, cholera toxin, bovine hypothalamus extract, and retinol. HTBE cells did not express any mucociliary function (ciliogenesis or mucin secretion) on tissue culture plastic, but they could be passaged 3 to 5 times with a total of 10 to 25 population doublings. Cells from early passages re-express both these functions when transplanted to tracheal grafts. When tissue culture plates were coated with collagen film or collagen gel substrata, cell attachment and proliferation were stimulated. However, the expression of mucous cell function in culture occurred only when cells were plated on collagen gel substrata and vitamin A (retinol) was present in the medium. Mucous cell differentiation under optimal conditions was defined by ultrastructural studies, by immunologic studies with mucin-specific monoclonal antibodies, and by carbohydrate and amino acid compositional analyses of mucin-like glycoproteins purified from culture medium. These results demonstrate for the first time that HTBE cells can express mucin synthesis and secretion under appropriate culture conditions.

Amino Acids↗
PubMed1990

Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome.

Oxidative stress has been implicated in the adult respiratory distress syndrome (ARDS). In this study, we determined the levels of selected antioxidants in the plasma of 25 patients with ongoing ARDS and 16 healthy control subjects. We also examined these plasmas and pulmonary edema fluid of ARDS patients for lipid hydroperoxides. Both ascorbate and ubiquinol-10 concentrations in ARDS plasma were significantly lower than in normal plasma. alpha-Tocopherol concentrations, when standardized to total plasma cholesterol, were not lower in ARDS patients than in normal subjects. A pattern of antioxidant levels virtually identical to that observed in ARDS plasma was obtained after in vitro incubation of healthy plasma with stimulated polymorphonuclear leukocytes: very low ascorbate, decreased ubiquinol-10, and unchanged alpha-tocopherol concentrations. Nanomolar concentrations of lipid hydroperoxides were found in pulmonary edema fluid of ARDS patients, but not in plasma, nor in the plasma of healthy individuals, when a sensitive and selective chemiluminescence assay for hydroperoxides was used. ARDS patients also showed significant decreases in plasma levels of cholesterol esters in conjunction with discoidal high-density lipoprotein profiles, indicating a decrease in lecithin-cholesterol acyltransferase activity. We conclude that ARDS is associated with oxidative stress, possibly exerted by oxidants released from activated phagocytic leukocytes, and major changes in plasma cholesterol metabolism.

Adult↗
PubMed1989

Ozone-induced accelerated lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the lungs of unanesthetized sheep exposed to varying concentrations of O3 for 4 h in a whole-body exposure chamber. Four sheep exposed to 1 ppm O3 had a monoexponential T50 of 274 +/- 81 min (SD), not significantly different from sham exposures (316 +/- 150); 5 sheep exposed to 2 ppm had a T50 of 234 +/- 101 min, not significantly different from sham exposures (364 +/- 131 min). Five additional unanesthetized sheep exposed to 2 ppm for 4 h via a nasotracheal tube had a T50 of 192 +/- 55 min, significantly different from sham exposures (300 +/- 96 min). The results show that the effect of oxidant pollutants on the permeability of alveolobronchiolar epithelium may be assessed in conscious sheep.

Aerosols↗
PubMed1988

Lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the whole lung in a group of 9 sheep. Submicronic aerosol droplets were delivered to unsedated sheep held in a sling-like frame. Best fits for clearance curves to single- and biexponentials were calculated. The monoexponential T50 for the aerosol clearance was 293 min +/- 74 SD. Background correction was found to have a minimal effect (approx. 10%). Biexponential fitting only marginally improved correlations in the 8 healthy sheep, but in one additional animal with clinical evidence of pneumonia, clearance was faster and biexponential fitting was substantially better. These clearance values in conscious sheep are longer than previous findings with 99mTc-DTPA in anesthetized sheep. There appears to be a wide variation of radioaerosol 99mTc-DTPA lung clearances among different species, sheep exhibiting a comparatively prolonged clearance profile.

Administration, Inhalation↗