Biomedical subjects

P C Panus

Publications and source records attributed to P C Panus.

25 records · Page 2Linked to original sources

PubMed1989

Development of O2 tolerance in rabbits with no increase in antioxidant enzymes.

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.

Animals↗

PubMed1988

Pulmonary metabolism of reactive oxygen species.

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.

Adaptation, Physiological↗

PubMed1987

Inhibition of neutrophil response by mepacrine.

Clinical and experimental evidence supports neutrophil involvement in the pulmonary complications of adult respiratory distress syndrome. Preliminary evidence indicates that mepacrine salvages pulmonary function in experimental models of adult respiratory distress syndrome, possibly by inhibiting neutrophil activation [E. M. Canham et al., Am. Rev. resp. Dis. 127, 594 (1983)]. This study examines the effect of mepacrine on neutrophil responses involved in pulmonary dysfunction associated with adult respiratory distress syndrome. A comparison is made between the ability of mepacrine to inhibit a specific neutrophil response utilizing different stimuli and the ability to inhibit different neutrophil responses to a single stimulus. Neutrophils were activated by a soluble stimulus, phorbol myristic acetate, and a particulate stimulus, heat-inactivated opsonized group B streptococcus. Mepacrine inhibited superoxide production in response to both phorbol myristic acetate (IC50 = 5.3 +/- 1.2 microM) or opsonized group B streptococcus (16.1 +/- 1.7 microM). Chemotaxis in response to n-formylmethionylleucylphenylalanine was also inhibited (41.1 +/- 2.2 microM). Finally, aggregation stimulated by either streptococcus or phorbol myristic acetate was inhibited by mepacrine (73.0 +/- 9.8 microM and 77.0 +/- 19.2 microM respectively). A comparison of the IC50 values demonstrates that the inhibitory effect of mepacrine is response dependent and stimulus independent. The results of this study are consistent with the proposal that mepacrine protects against the pulmonary complications associated with adult respiratory distress syndrome by its action as an inhibitor of neutrophil function.

Cell Aggregation↗

PubMed1987

Characterization of polymorphonuclear leukocyte aggregation in vitro induced by heat-inactivated group B streptococcus.

We studied the aggregatory characteristics of human polymorphonuclear leukocytes (PMNs) in response to heat-inactivated group B streptococcus. PMNs suspended in physiologic salt solution do not aggregate to heat-inactivated group B streptococcus (GBS) unless the GBS is previously opsonized in autologous plasma. The aggregating activity of both opsonized GBS and activated plasma are reduced if the plasma is decomplemented before incubation with GBS. Pretreatment of PMNs with pronase inhibited opsonized GBS-induced aggregation, suggesting aggregation via cell membrane receptors for opsonic fragments of C3. Pronase pretreatment had no significant effect on aggregation induced by activated plasma or arachidonic acid. Unlike PMNs in physiologic salt solution, PMNs suspended in plasma aggregate when stimulated by unopsonized GBS. GBS aggregates PMNs via complement cascade activation, opsonization, and interaction with cell membrane receptors to stimulate cellular mechanisms resulting in PMN aggregation.

Bacterial Vaccines↗

PubMed1987

In vitro inhibition of group B streptococcus-induced polymorphonuclear leukocyte aggregation.

Evidence suggests that part of the pathophysiologic response seen in group B streptococcal (GBS) sepsis may be due to polymorphonuclear leukocyte (PMN) activation. Indomethacin (INDO), which inhibits eicosanoid metabolism, attenuates the pathophysiologic response stimulated by GBS, possibly due to inhibition of PMN aggregation. We examined the capability of two eicosanoid metabolism inhibitors, INDO and nordihydroguaiaretic acid (NDGA), to inhibit PMN aggregation induced by heat-inactivated opsonized GBS and GBS-activated plasma. Opsonized GBS-induced PMN aggregation was inhibited by INDO (50-500 microM) and NDGA (1-100 microM). Over similar concentration ranges, INDO and NDGA had no significant effect on PMN aggregation induced by GBS-activated plasma. PMNs in plasma aggregate in response to unopsonized GBS. The stimuli for aggregation are opsonized GBS and GBS-activated plasma. INDO (50-500 microM) was unable to inhibit aggregation under this condition. Over the same concentration range in which INDO inhibited opsonized GBS-induced PMN aggregation, INDO was unable to inhibit opsonized GBS-induced superoxide production in PMNs. NDGA was examined but was found to interfere with the assay. The above evidence suggests PMN aggregation via eicosanoid metabolism may play a role in GBS-induced sepsis, which may be attenuated by agents such as INDO and NDGA.

Bacterial Vaccines↗

PubMed1985

Measurement of malonyldialdehyde production during sodium arachidonate-induced polymorphonuclear leukocyte aggregation.

Sodium arachidonate stimulated canine polymorphonuclear leukocytes (PMNs) to aggregate and produce malonyldialdehyde (MDA). The MDA production was due to cellular processes during the aggregation, as boiled PMN suspension neither aggregated nor produced MDA. Aggregation and MDA production were not due to platelet contamination because epinephrine and ADP were unable to stimulate either of these responses in the PMN suspensions. Finally, use of the aggregatory modifiers indomethacin, 1-methylimidazole, and vitamin E dissociated aggregation from MDA production. These results suggest that the cellular process(es) resulting in MDA production is/are not responsible for canine PMN aggregation.

Adenosine Diphosphate↗

PubMed1984

Sodium arachidonate induced in vitro polymorphonuclear leukocyte aggregation.

Human polymorphonuclear leukocytes (PMNs) aggregated to sodium arachidonate (AA) in a dose dependent manner. Other agents such as epinephrine, or ADP were unable to initiate aggregation. The cells released lactate dehydrogenase (LDH) during aggregation, and electron microscopy demonstrated distinct morphologic changes in PMNs aggregated with AA. Indomethacin enhanced AA induced aggregation, whereas 1-methylimidazole inhibited aggregation and LDH release. Preincubation with cytochalasin B (CTB) did not enhance AA induced aggregation, nor did it reduce LDH release. Also, the effects of indomethacin or 1-methylimidazole on AA induced aggregation were unaltered by the presence of CTB. The results indicate that 1) LDH release occurs as a function of the aggregation process rather than a non-specific effect, 2) competition between cyclooxygenase and lipoxygenase occurs and 3) shifting this competition in favor of lipoxygenase enhances the PMN aggregation process.

Arachidonic Acid↗