Biomedical subjects

E Putman

Publications and source records attributed to E Putman.

5 recordsLinked to original sources

PubMed2003

Assessing immunotoxicity: guidelines.

Over the last couple of years the assessment of immunotoxic potential of human pharmaceuticals has drawn considerable attention worldwide. Regulatory agencies entrusted with the registration of pharmaceuticals (or other compounds) found an increased need for guidance on this issue. This has resulted in the release of guidance documents on immunotoxicity in Europe, USA and Japan in close succession. In Europe the CPMP has released their immunotoxicity guidance documents that are now in force. The FDA and the Japanese Authorities are in the process of doing so, and will shortly enforce them. Immune suppression and stimulation, hypersensitivity, photosensitivity, drug-induced autoimmunity and developmental immunotoxicity are the focus of regulatory testing. This review discusses these kinds of immunotoxicity and their clinical implications. The three regional guidelines and screening tools for detection are discussed. Additionally, the scientific background on which these guidelines are based is briefly highlighted.

Adjuvants, Immunologic↗

PubMed1997

Short-term ozone exposure affects the surface activity of pulmonary surfactant.

The effects of short-term ozone exposure on the lung function and surface activity of surfactant subtypes isolated from rat lung lavage were studied. Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The surface activity of surfactant was affected by ozone exposure, whereas distinct morphological changes in bronchoalveolar lavage or in the surfactant subtypes were not observed. Adsorption experiments indicated that bronchoalveolar lavage from rats exposed for 12 hr to ozone remained at lower equilibrium surface pressures than lavage from control rats. These observations suggest interference of inflammatory proteins with the surface film. Extracted surfactant, containing only lipids and surfactant proteins B and C, had a decreased adsorption rate after ozone exposure. These results suggest that the activity of one or both of the hydrophobic surfactant proteins (SP-B and SP-C) was affected by ozone.

Administration, Inhalation↗

PubMed1997

Toxic oxidant species and their impact on the pulmonary surfactant system.

In this review the effects of oxidant inhalation on the pulmonary surfactant system of laboratory animals are discussed. Oxidant lung injury is a complex phenomenon with many aspects. Inhaled oxidants interact primarily with the epithelial lining fluid (ELF), a thin layer covering the epithelial cells of the lung which contains surfactant and antioxidants. In the upper airways this layer is thick and contains high levels of antioxidants. Therefore oxidant injury in this area is rare and is more common in the lower airways where the ELF is thin and contains fewer antioxidants. In the ELF oxidants can react with antioxidants or biomolecules, resulting in inactivation of the biomolecules or in the formation of even more reactive agents. Oxidation of extracellular surfactant constituents may impair its function and affect breathing. Oxidized ELF constituents may promote inflammation and edema, which will impair the surfactant system further. Animal species differences in respiratory tract anatomy, ventilatory rate, and antioxidant levels influence susceptibility to oxidants. The oxidant exposure dose dictates injury, subsequent repair processes, and tolerance induction.

Animals↗

PubMed1996

Surface properties, morphology and protein composition of pulmonary surfactant subtypes.

Separation of surfactant subtypes is now commonly used as a parameter in assessing the amount of active compared with inactive material in various models of lung injury. The protein content, morphology and surface activity were determined of the heavy and light subtype isolated by differential centrifugation. Here we report the presence of surfactant proteins B and C in the heavy subtype but not in the light subtype. Adsorption studies revealed that separation of fast adsorbing bronchoalveolar lavage resulted in slowly adsorbing heavy and light subtypes. Surfactant, reconstituted from heavy and light fractions, did not show a high adsorption rate. It is concluded that the isolation procedures might result in a loss of fast adsorbing surfactant structures. Surface area cycling was used as a model in vitro for the extracellular surfactant metabolism. The heavy subtype is converted into the light subtype during conversion. Conversion performed with resuspended heavy subtype revealed the generation of a disparate subtype. Furthermore it was found that the conversion was dependent on preparation and handling of the samples before cycling. Finally, adsorption studies at low surfactant concentrations revealed a delayed adsorption of lipid-extracted surfactants compared with natural surfactants. These observations emphasize the importance of the (surfactant-associated protein A-dependent) structural organization of surfactant lipids in the adsorption process.

Adsorption↗

PubMed1995

Pulmonary surfactant subtype metabolism is altered after short-term ozone exposure.

Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The latter condition resulted in lung damage and inflammation while the former did not. Directly after exposure surfactant was isolated and two morphologically and functionally different surfactant subtypes were obtained by differential centrifugation. Surfactant subtypes isolated from rats exposed to 0.8 ppm ozone for 2 and 12 hr showed an increase in the amount of heavy subtype and a decrease in light subtype. These results suggest that acute ozone exposure of rats can alter surfactant subtype composition. The conversion in vitro of heavy to light subtype was increased in ozone-exposed rats. Degradation of surfactant protein A (SP-A) was observed during in vitro conversion of heavy subtype isolated from ozone-exposed rats. This suggests that oxidation of SP-A may lead to enhanced susceptibility for degradation. The observed effects were more pronounced in rats exposed for 12 hr than those exposed for 2 hr, indicating that proteolytic enzymes from inflammatory cells may aggravate the observed effects. We conclude that extracellular surfactant metabolism is altered by short-term exposures to ozone and that oxidation of SP-A may contribute to the observed alterations.

Animals↗