Biomedical subjects

A M Hooke

Publications and source records attributed to A M Hooke.

24 records · Page 2Linked to original sources

PubMed1985

Ibuprofen modifies the inflammatory response of the murine lung to Pseudomonas aeruginosa.

In chronic P. aeruginosa infection, lung tissue damage is induced by either the microorganism or the inflammatory response. We investigated, in an animal model, whether a non-steroidal anti-inflammatory drug, ibuprofen, reduced lung inflammation produced by P. aeruginosa. Lung lavages, pulmonary clearance of P. aeruginosa and lung pathology were studied in CD-1 mice injected with sodium ibuprofenate. A single dose of the drug, injected immediately after 30 min exposure to the P. aeruginosa aerosol, decreased the recruitment of granulocytes into airways in a dose-dependent manner. Pretreatment with 2 doses of the drug 18 and 6 h before the P. aeruginosa challenge was even more effective. The kinetics of changes in prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 concentrations in lung lavage fluids after P. aeruginosa aerosol were also modified by ibuprofen. Moreover, ibuprofen treatment did not impair lung clearance of the challenge microorganisms, and the animals had less inflammation of the lungs.

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Enhancement of Pseudomonas aeruginosa lung clearance after local immunization with a temperature-sensitive mutant.

We investigated the capacity of the temperature-sensitive mutant strain A/10/25 of Pseudomonas aeruginosa (ts-Psa) to induce enhancement of lung defenses against wild type P. aeruginosa (wt-Psa). Mice of the DBA/2J inbred strain were immunized by aerosolization with a single dose of 2 x 10(5) to 4 x 10(5) CFU of ts-Psa and were challenged 7, 14, and 21 days later with wt-Psa. The uncleared bacteria ratio was determined 4 h after aerosol exposure; significant enhancement in lung clearance of wt-Psa (P less than 0.01) was evident as early as 7 days after immunization and detectable for at least 21 days. Aerosol immunization with Staphylococcus aureus did not enhance lung clearance of wt-Psa; however, slight but significant enhancement in S. aureus clearance was observed in mice immunized 7 days before with ts-Psa. No enhancement of S. aureus clearance was seen in ts-Psa immunized animals after 14 and 21 days. Analysis of the cell composition of lung lavage fluids revealed a transient cell response characterized by rapid increase in the absolute number of polymorphonuclear leukocytes, followed later by an increase in alveolar macrophages. The characteristics of lung lavages returned to base-line values 6 days after aerosol immunization, and a second exposure to a ts-Psa aerosol produced a response of similar magnitude and quality. We conclude that aerosol immunization with a temperature-sensitive mutant of P. aeruginosa enhances specific pulmonary defense mechanisms against the parental pathogen in mice.

Aerosols↗

PubMed1983

Pulmonary clearance of Staphylococcus aureus and plasma angiotensin-converting enzyme activity in hydrocarbon pneumonitis.

Pulmonary clearance of Staphylococcus aureus and plasma angiotensin-converting enzyme (ACE) activity were investigated in an experimental mouse model of kerosene aspiration. Twenty-four hours after acute kerosene aspiration, mice were exposed for 30 min to an aerosol containing the pathogen, and the uncleared bacteria ratio (UBR) determined 4 h after nebulization. The results showed a significant increase (P = 0.004) in UBR in animals with severe pneumonitis (0.44 +/- 0.05) when compared with controls (0.24 +/- 0.03). This impairment in lung clearance correlated with the increase in lung weight and the decrease in plasma ACE levels. Mice with kerosene pneumonitis had zones of lung injury, and areas with no gross signs of tissue damage. Lung clearance of S. aureus was significantly impaired in damaged areas whereas it was no different from controls in the non-affected areas. It is suggested that the measurement of plasma ACE activity may be an adjunct in the assessment of the extent of lung injury in hydrocarbon aspiration in children.

Animals↗

PubMed1982

Temperature-sensitive mutants of Pseudomonas aeruginosa: isolation and preliminary immunological evaluation.

The immunogenicity of two temperature-sensitive (ts) mutants of Pseudomonas aeruginosa immunotype 1, isolated and characterized for the development of a safe, live vaccine strain, was evaluated in a mouse protection model. One mutant, A/10/25, had a limited "coasting" property (i.e., continued replication for two divisions) at the nonpermissive temperature (36 degrees C), whereas the other mutant, E/9/9, continued replication for five generations after transfer to 36 degrees C. Groups of 3- to 5-week-old ICR mice were immunized intraperitoneally with various doses of the two ts mutants; at various times thereafter, the mice were challenged intraperitoneally with lethal doses of the parental wild type. The more extensive coaster, E/9/9, induced 100% protection at immunizing doses lower than those required for A/10/25 to induce the same protection (1 x 10(8) to 2 x 10(8) and 6 x 10(8) colony-forming units, respectively). Both ts strains induced significant protection for up to 5 weeks after immunization. The results of these studies suggest that the use of P. aeruginosa ts mutants might provide a novel approach to the prevention of P. aeruginosa colonization of patients with cystic fibrosis.

Animals↗

PubMed1978

Ideal target organism for quantitative bactericidal assays.

We have developed a target organism which permits quantitative bactericidal assays. The organism is an Escherichia coli mutant which cannot grow at the temperature of the assay (37 degrees C), but retains full colony-forming potential for subsequent quantitation at 25 degrees C. We show that quantitative data on the bactericidal capacity of polymorphonuclear leukocytes and alveolar macrophages can be obtained when this mutant is used as a target. The procedure used to generate the strain is described in detail and should be applicable to many bacterial species. Characterization of the properties of the mutant indicates that it has a strong potential for use in other in vivo and in vitro investigations of host responses to microbial invasion.

Animals↗

PubMedDate not supplied

The effect of liposomal cefoperazone against Pseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection.

The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.

Acute Disease↗