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Biomedical subjects

A F Tryka

Publications and source records attributed to A F Tryka.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxin shock.

The role of the polymorphonuclear leukocyte in the development of acute lung injury has been the subject of much controversy. Experimental lung injury is associated with peripheral leukopenia and the intrapulmonary sequestration of leukocytes. We have previously shown that ibuprofen, a nonsteroidal anti-inflammatory drug, can improve the hemodynamic alterations of canine endotoxin shock. Ibuprofen has also been found to decrease leukocyte adherence. We investigated the dose response of ibuprofen on the increased neutrophil adherence and the extent of lung injury associated with canine endotoxin shock. Single doses of ibuprofen (1, 5, 10, and 20 mg/kg iv) were administered 15 min after Escherichia coli endotoxin. Endotoxemia resulted in leukopenia and an increased neutrophil adherence in both aortic and pulmonary artery blood. Endotoxin-treated animals exhibited increased neutrophils in the bronchoalveolar lavage fluid, a marker of lung injury. The 20-mg/kg ibuprofen dose decreased aortic granulocyte adherence at 30 min, while all ibuprofen doses decreased the aortic adherence at 120 min. The increased pulmonary artery neutrophil adherence was not affected by ibuprofen. Histologically, lung injury was manifested by intravascular leukostasis. Ibuprofen treatment did not affect the histologic or morphometric extent of the lung injury. The leukopenia and increased neutrophil adherence occur rapidly after endotoxemia and are associated with subsequent intravascular sequestration of leukocytes. Agents designed to prevent lung injury must either be given before the insult or be able to block the effects of the toxic products released by the activated granulocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Low dose ibuprofen reverses the hemodynamic alterations of canine endotoxin shock.

The dose response of the nonsteroidal anti-inflammatory drug, ibuprofen, was evaluated in order to determine the most efficacious dose in the treatment of canine endotoxin shock. Fifteen minutes after an infusion of Escherichia coli endotoxin, four groups of dogs were given a single iv dose of 1, 5, 10, or 20 mg/kg of ibuprofen. These groups were compared to endotoxin only and saline control groups. All ibuprofen doses significantly improved the systolic, diastolic, and mean systemic arterial BP. The improvement in systemic BP was accompanied by an increase in the systemic vascular resistance. Pulmonary vascular pressures and resistance also increased after ibuprofen administration. The lack of a dose response and the demonstrated beneficial effect of low dose ibuprofen in the reversal of the hypotension associated with experimental canine endotoxin shock lead us to recommend the use of low dose ibuprofen for future endotoxin and sepsis studies. Use of low dose ibuprofen might have less of an effect on renal perfusion and would therefore be more likely to produce the beneficial hemodynamic response without compromising renal function.

Animals↗
PubMed1988

Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury.

Bacterial sepsis and pneumonia are common complications of lung injury and predispose the host to a poor resolution. We studied the functional integrity of pulmonary macrophages derived from minced lung preparations in a canine model of endotoxin-induced shock with acute lung injury. Dogs given 2 mg/kg of Escherichia coli endotoxin 055:B5 developed classic shock symptoms with concomitant acute lung injury; control animals given saline showed no physiological or pathological abnormalities. Compared to previous work with this canine model, the lung injury in this extended time period (6 h) had progressed to include alveolar edema. Six hours after endotoxin infusion, the left lung was lavaged, perfused, and the resulting lung minced for isolation of pulmonary macrophages. The endotoxic-model pulmonary macrophages showed several significant functional differences from controls. Although they elicited greater production of H2O2 (p less than 0.05), both phagocytosis of radiolabeled Staphylococcus aureus and E. coli (p less than 0.05) and bactericidal activity (p less than 0.05) were diminished compared to controls. Compared to alterations previously described in alveolar macrophages, these cells produced less H2O2 and demonstrated abnormal bacterial killing at all time points. These observations suggest that the functional alterations of pulmonary macrophages that follow acute lung injury contribute to the ineffective cell-mediated antimicrobial response. These derangements may promote an increased risk of nosocomial pneumonia, the high mortality often observed subsequent to pneumonia, or the propagation of acute lung injury that facilitates respiratory failure.

Animals↗
PubMed1987

Acute respiratory failure induced by bleomycin and hyperoxia: pulmonary edema, cell kinetics, and morphology.

The acute manifestations of experimental bleomycin- and hyperoxia-induced lung damage were examined. Hamsters were treated with 5 U/kg bleomycin intratracheally followed by exposure to 80% oxygen (O2). As little as 12 hr of O2 exposure potentiated the bleomycin injury; however, the onset of mortality was 72 hr after treatment. The onset of pulmonary edema, measured by radiolabeled tracers, also occurred 72 hr after treatment. Cell kinetics studies showed that 24 hr exposure to 80% O2 did not alter early alveolar cell proliferation. Treatment with bleomycin alone did result in an early increase in alveolar macrophage and type II pneumocyte labeling. Animals treated with both bleomycin and hyperoxia had an increase in macrophage labeling, but not in type II pneumocyte labeling. We conclude that increased macrophage numbers associated with suppressed type II pneumocyte proliferation may play key roles in the potentiation and development of lung damage caused by bleomycin and hyperoxia treatment.

Animals↗
PubMed1987

Modification of gastrointestinal tumor development in rats by dietary butylated hydroxytoluene.

Male Fischer 344 rats were given two or four injections of 1,2-dimethylhydrazine (DMH), 40 mg/kg sc, and then fed a diet containing 0.5% butylated hydroxytoluene (BHT). Five months later, the animals treated with two doses of DMH had a significantly higher incidence of colon tumors than the animals fed a BHT-free control diet. In animals treated with four injections of DMH, the increase in colon tumor incidence was statistically not significant, but BHT appeared to produce a shift in tumor distribution. In a second experiment, Fischer 344 rats were treated with 2 X 40 mg/kg of DMH and fed a diet of 0.5 or 0.1% BHT for 6 months; these animals had a significantly increased incidence of small intestinal tumors (duodenum, jejunum, and ileum) compared with animals fed the control diet. In rats treated with DMH and given a diet of 0.5% butylated hydroxyanisole (BHA), overall incidence of gastrointestinal tract tumors was higher than in control animals, although the difference was statistically not significant. Administration of N-nitroso-N-methylurea (NMU; 90 mg/kg given orally) produced stomach and colon tumors; 0.5% BHT in the diet did not modulate tumor incidence. It is concluded that dietary BHT may enhance development of gastrointestinal tumors produced by DMH, but not by NMU, provided exposure to BHT occurs after exposure to the carcinogen.

Animals↗
PubMed1987

Gliosarcoma with chromosome abnormalities in a neonate exposed to heptachlor.

A neonate with a cerebral gliosarcoma was found to have chromosome abnormalities in tissue culture of the tumor, but normal karyotyping of peripheral blood. Similarities to and differences from chromosome abnormalities found in other human gliomas are noted. Unusual exposure of the child to heptachlor during prenatal development and the neonatal period suggests the need for further studies on the role of toxins in oncogenesis.

Animals↗
PubMed1986

Acute pulmonary toxicity of beryllium sulfate inhalation in rats and mice: cell kinetics and histopathology.

The acute response in the lung of mice and rats exposed to an aerosol of BeSO4 was characterized by cell kinetics and histopathology. Animals were exposed for 1 hour in a nose-only chamber to a 13 microgram/liter chamber concentration of BeSO4 or to H2SO4 as control aerosol, and killed thereafter over a period of 21 days. Lung cell kinetics were evaluated as the labeling index (LI), defined as the percentage of cells labeled with tritiated thymidine. The labeled cells were also differentiated as to type. In rats, the LI showed a peak response on Day 8 following exposure, while the LI of mice showed a maximum response at Day 5. In rats, the proliferative response involved type II alveolar epithelial cells, interstitial and capillary endothelial cells. Histopathology showed type II alveolar cell hyperplasia and vacuolization of their cytoplasm, a thickened interstitium with infiltrates of interstitial macrophages and segmental leukocytes; a prominent feature was alveolar macrophages with ragged membranes. Three weeks after exposure, the interstitial response was largely resolved. In mice, the proliferative response was mainly found in the alveolar macrophage population and the interstitial and endothelial cells. Histopathological changes were similar to those found in rats, although less severe.

Administration, Inhalation↗
PubMed1986

Changes in collagen cross-linking in bleomycin-induced pulmonary fibrosis.

Collagen cross-linking was analyzed in lungs of rats, two, four, and ten weeks after intratracheal instillation of 1.5 units of bleomycin. Similar analyses were performed on lungs of mice 18 months after intratracheal instillation of bleomycin with or without subsequent exposure to 70% oxygen (O2) for 72 hours. Lungs were analyzed to determine the content of the reduced difunctional cross-links dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL) and of the nonreducible trifunctional cross-link hydroxypyridinium (OHP). Ratios of DHLNL:HLNL were elevated in the rat lungs at two and four weeks, due to increased levels of DHLNL. There were no changes in the difunctional cross-links in any of the mouse lungs. Hydroxypyridinium content was elevated in the rat lungs at ten weeks and in the mouse lungs exposed to bleomycin and oxygen. We conclude that increases in DHLNL may serve as an early indicator that potentially "fibrotic collagen" is being synthesized in lungs acutely exposed to fibrogenic stimuli, while increases in OHP may serve as a permanent marker of a fibrogenic event that could have occurred months to years earlier.

Animals↗
PubMed1986

Intratracheal versus intravenous administration of bleomycin in mice: acute effects.

We examined whether intratracheal instillation (IT) of bleomycin would produce similar or dissimilar lesions when compared to lung damage following intravenous (iv) injection of the drug. BALB/c mice were treated with either 4 U/kg IT or 100 U iv bleomycin and killed at intervals up to 21 days after treatment. Cell proliferation, histopathology, lung lavage, and hydroxyproline content were examined. There was a biphasic response in the cell proliferation in the IT-treated mice, while the iv-treated mice showed a single delayed peak in proliferation. The histopathologic features of interstitial pneumonitis, elevation of lung lavage enzyme activities, and lung hydroxyproline content were qualitatively similar between the two routes of administration, although the IT mice response was always greater in magnitude. Differences exist between the lung reaction to these two routes of administration, but these differences reflect nonspecific inflammatory response and magnitude of initial injury. We conclude that the response to bleomycin administered IT is basically similar to the changes produced by intravenous injection of the drug.

Animals↗
PubMed1986

The effects of dietary butylated hydroxytoluene on liver and colon tumor development in mice.

Male and female C3H mice were fed a diet containing 0.5% or 0.05% of the antioxidant butylated hydroxytoluene (BHT). After 10 months, male but not female animals had a significantly increased incidence of liver tumors compared to animals kept on a BHT-free control diet. In a second experiment, male BALB/c mice were treated subcutaneously with the carcinogens dimethylhydrazine (DMH) or intrarectally with methylnitrosourea (MNU). A diet containing 0.5% BHT significantly increased the incidence of colon tumors in DMH treated animals but had no effect in mice given MNU. It is concluded that the effect of BHT on tumor development depends on strain and target organ examined and possibly also on the chemical carcinogen used.

1,2-Dimethylhydrazine↗
PubMed1986

Surfactant alterations following acute bleomycin and hyperoxia-induced lung damage.

Hamsters treated with 0.5 U/kg intratracheal bleomycin and exposed for 24 h to 80% O2 develop acute respiratory failure 72 h after treatment. To examine indirectly the lung epithelial type II cell changes, alterations in pulmonary surfactant was measured. Presence and amount of dipalmitoyl phosphatidyl choline (DDPC) and sphingomyelin (SM) were measured, and the DPPC/SM ratio was determined in brochoalveolar lavage samples from treated and control animals 24, 48, 72, and 96 h after treatment. Hamsters treated with bleomycin and O2 had a significantly decreased DPPC/SM ratio at 72 h, which is the time of onset of respiratory failure. The decreased DPPC/SM ratio may reflect type II cell damage and inhibition of surfactant function by the edema fluid.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

Attenuated pulmonary vascular obstructive disease in double-outlet right ventricle and mitral stenosis.

A young woman with double-outlet right ventricle, mitral stenosis, and high systemic pulmonary artery pressure is described. Pulmonary vascular morphometric analysis indicated considerably less pulmonary vascular obstructive disease than might otherwise have been expected. Total repair was performed and resulted in a marked fall in pulmonary artery pressure. Pulmonary vascular morphometry may be indicated in selected patients before palliative management is selected over complete repair.

Adult↗
PubMed1986

Patterns of cell proliferation during recovery from oxygen injury. Species differences.

Do rats, mice, hamsters, and marmosets respond differently to acute lung injury? Animals of each species were exposed to 100% oxygen for 48 h, then osmotic pumps, which released 3H-thymidine for a 1-wk period, were implanted. The labeling index (LI) (cells labeled/total cells counted) was increased in all 4 species. Repair in rats was manifested by a high LI, dominated by endothelial cell proliferation. Mice and hamsters had a lower LI, which was dominated by type II pneumocyte proliferation in mice, whereas in hamsters, macrophages and pneumocytes proliferated. The pattern of cell proliferation in marmosets most resembled that seen in mice.

Animals↗
PubMed1986

Inhibition of mouse lung tumor development by hyperoxia.

The hypothesis was tested that continuous hyperoxia would enhance the development of lung tumors in mice. In strain A/J mice treated with a single dose of urethan (1000 mg/kg) and exposed to 70% O2 for 16 wk, an average of 5 tumors per lung developed, whereas in animals kept in air, an average of 20 tumors per lung was found. When the animals were returned to air after oxygen exposure, it was found that a difference of 15 tumors per lung between the two groups persisted up to 1 yr later, indicating that O2 was tumoricidal. The shortest duration of O2 exposure to be effective was 4 wk, and delay of O2 exposure up to 12 wk after urethan still was effective in reducing the number of developing tumors. Histopathology showed that continued exposure to 70% O2 produced some hyperplasia of the bronchiolar epithelium and only very discrete changes in the pulmonary parenchyma. Analysis of cell proliferation patterns with a continuous [3H]thymidine labeling technique showed a persistent high cell labeling in the bronchiolar epithelium and a temporary increase in alveolar wall cell labeling. Chronic hyperoxia failed to alter the activities of pulmonary superoxide dismutase or glucose-6-phosphate dehydrogenase. Ornithine decarboxylase, on the other hand, was increased as long as the animals remained exposed to oxygen. It was concluded that hyperoxia kills developing tumor cells in mouse lung.

Animals↗
PubMed1985

Progressive pulmonary fibrosis in rats: a biochemical, cell kinetic, and morphologic analysis.

The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.

Animals↗
PubMed1985

The many faces of an increase in lung collagen.

Many toxic chemicals have been shown to produce an increase in lung collagen. Biochemical measurements of total lung hydroxyproline are a convenient method to quantitate and to follow disease processes associated with such an increase. However, biochemical measurements alone do not distinguish various pathological lesions and histology is needed to provide additional important information. Cell kinetic studies enhance histopathology in showing the dynamics of cell proliferation and tissue renewal. When these methods of studying lung collagen are applied to different toxic agents, such as butylated hydroxytoluene, methylcyclopentadienyl manganese tricarbonyl, CdCl2, or anticancer drugs, different patterns of hydroxyproline accumulation and cellular kinetics are revealed. It is speculated that the development of fibrotic lung disease may be at least partially determined by the initial lesion and that quantitative analyses of cell kinetic patterns help to understand and to predict the nature and evolution of disease processes.

Animals↗
PubMed1985

Pulmonary vascular disease and hypertension after valve surgery for mitral stenosis.

The reduction of pulmonary hypertension that occurs within 24 hours of valve replacement for mitral stenosis is well documented, but patients who die after surgery have not been adequately studied. Clinical and autopsy data for 16 patients who died following mitral valve replacement were reviewed. The emphasis was on preoperative and postoperative pulmonary arterial pressure and pulmonary vascular disease, including arterial, venous, and capillary changes. Morphologic features were graded and summed to obtain an additive histologic assessment (AHA). Patients were divided into three groups: 1) those who had uneventful operations and early postoperative periods but died prior to discharge; 2) those who had postoperative difficulty, with identifiable acute anatomic causes of death; and 3) those who had postoperative difficulty, with no apparent acute anatomic cause of death. In group 1 (n = 4) the preoperative pulmonary arterial pressure was 43 +/- 17 mm Hg, and AHA ranged from 0 to 4; in group 2 (n = 5) the preoperative pulmonary arterial pressure was 60 +/- 15 mm Hg, but AHA ranged only from 2 to 5. In group 3 (n = 7) the preoperative pulmonary arterial pressure was 59 +/- 12 mm Hg; AHA ranged from 6 to 9, significantly higher than that of the other groups (P less than 0.005). Three patients from group 3 had elevated pulmonary arterial pressure (60, 52, and 50 mm Hg three, six, and 15 days after surgery, respectively). Two additional patients had right heart failure with normally contracting left ventricles terminally. It is concluded that some patients with mitral stenosis who die after surgery with persistently elevated pulmonary arterial pressure have sufficiently severe pulmonary vascular disease to account for their persistent pulmonary hypertension and death.

Adult↗