A model of cigarette smoke particle deposition.

A computer model of aerosol deposition has been extended to cover particle sizes representative of cigarette mainstream and sidestream smoke particles. The model is the first to theoretically predict total airway depositions of mainstream particles in a range which agrees with experimentally determined literature values by including effects of hygroscopicity and normal smoking breathing patterns. The hygroscopic characteristics of cigarette smoke particles are modeled as if they were saturated sodium chloride droplets. A discussion is included showing that this assumption is consistent with presently available data on the hygroscopic characteristics of cigarette smoke. Detailed regional depositions are provided. Though most of the particles are shown to deposit in the periphery, the surface concentrations of deposited particles are not necessarily much greater there than in centrally located airways. A peak in surface concentration at the third generation is exhibited, despite low total depositions there. Central airway surface concentrations are shown to be relatively independent of breathing pattern and airway geometry, implying that the effects of cigarette smoke particle deposition cannot be greatly reduced by changing the pattern of smoke inhalation. For sidestream smoke particles, total percent depositions agree with literature values of 7%-20% for both nonhygroscopic and hygroscopic particles. Deposition is seen to be favored in the periphery of the lung, though surface concentrations of the deposited material can be greater in Weibel Generations 3-6. Peak surface concentrations are again seen to occur in Generation 3. The increased toxicity of sidestream smoke particles may make them as unhealthy as mainstream smoke particles, despite the higher depositions observed for mainstream smoke.

Density-independent isolation of type II pneumocytes after partial pneumonectomy.

Type II pneumocytes were isolated by immunoglobin G (IgG) panning from the lungs of normal rats and the right lung of rats (180-200 g) subjected to left pneumonectomy. Cells were studied at 7 (pnx-7) and 15 (pnx-15) days postoperative, times during and after, respectively, rapid compensatory growth of the right lung. After 24 h of primary culture, pnx-7 cells contained 32% more protein per DNA, and incorporated thymidine at a rate 224% greater than cells isolated from control rats. Both the protein-to-DNA ratio and thymidine incorporation returned to control values in pnx-15 cells. Uptake of exogenous spermidine also was increased by 50% in pnx-7 cells at 24 h of primary culture and returned to control values in pnx-15 cells. Increased spermidine uptake was due to an increase in the maximal velocity (Vmax) of transport from 30.3 (control) to 45.5 pmol.micrograms DNA-1.h-1 (pnx-7), with no change in the apparent Km of 1.32 microM. No change was observed in the relative rates of phospholipid or neutral lipid biosynthesis. The increases in thymidine incorporation and spermidine uptake were significantly greater than those previously observed [Am. J. Physiol. 254 (Cell Physiol. 23): C684-C690, 1988] in pnx-7 cells isolated by Percoll gradient sedimentation. These results suggest that pnx-7 lungs contain distinct subpopulations of type II pneumocytes, the recovery of which is dependent on the cell isolation protocol employed.

Endogenous opioid systems and neural development: ultrastructural studies in the cerebellar cortex of infant and weanling rats.

Endogenous opioid systems participate in regulating the development of the nervous system. Opioid antagonists like naltrexone (NTX) perturb the relationship between endogenous opioids and opioid receptors quite effectively and reveal the function(s) of endogenous opioid systems during neuro-ontogeny. In this study, the effects of NTX, as well as the repercussions of modulation of endogenous opioid systems during critical stages of neural ontogeny, have been examined at the electron microscopic level of resolution in infant (10 day) and weanling (21 day) rats. Preweaning rats were subjected to complete (50 mg/kg NTX) or intermittent (1 mg/kg NTX) daily receptor blockade. Extensive ultrastructural examinations were conducted on the external germinal (granule), molecular, Purkinje, internal granule, and medullary layers of the cerebellar cortex. The NTX groups had striking similarities in morphology to that of controls at postnatal days 10 and 21. These results support the hypothesis that endogenous opioid systems act as trophic factors as they regulate growth; their effects on cell growth and survival, however, do not alter the basic ultrastructural morphology of the cells. Moreover, these data further strengthen the validity of paradigms utilizing opioid antagonists to explore the relationship of endogenous opioid-opioid receptor interactions and neural morphogenesis.

Airway deposition of hygroscopic heterodispersed aerosols: results of a computer calculation.

A new computer model is developed and used to calculate the deposition of inhaled heterodispersed hygroscopic aerosols for mouth breathing in a Weibel symmetric bronchial tree. The model was first validated by obtaining good agreement with recent experimental and theoretical data on regional and total airway deposition of monodispersed and heterodispersed nonhygroscopic aerosols. The model was then used to obtain predictions of regional and total deposition of heterodispersed hygroscopic aerosol particles (droplets of NaCl solutions). Parameters that were varied in the hygroscopic calculations include initial droplet NaCl concentration, time of inspiration and expiration, volume of aerosol inspired, period of breath holding, and initial inhaled lognormal aerosol mass median diameter and geometric standard deviation. Results of the computer calculations show that increasing heterodispersity tends to flatten and broaden regional deposition curves when fraction of inhaled mass deposited is plotted vs. inhaled mass median aerodynamic particle diameter. Hygroscopicity is shown to increase tracheobronchial and pulmonary airway deposition with hypertonic NaCl solution aerosols showing increases over isotonic and nonhygroscopic aerosols of up to 200%.

Maximization of pulmonary hygroscopic aerosol deposition.

A newly developed computer model is used to predict the aqueous salt solution concentration, breathing pattern, and inhaled droplet size distribution parameters that will maximize pulmonary deposition of hygroscopic medicinal aerosols. The parameter values providing maximum pulmonary deposition include 1) a NaCl concentration in the aerosolized solution of 0.035 g/ml or higher if the subject can tolerate it, 2) as nearly a monodispersed inhaled aerosol size distribution as possible, 3) an aerosol mass median diameter of 2-3 micron, and 4) slow (7 breaths/min) uninterrupted breathing of 1.5-2 liters of aerosol/breath. With these values, the model predicts that pulmonary deposition can be increased by greater than 100% relative to the deposition achieved in conventional inhalation therapy with isotonic saline-based medications.

Changes in the mechanisms of hormone and neurotransmitter action during aging: current status of the role of receptor and post-receptor alterations. A review.

Alterations in responsiveness to hormones and neurotransmitters during aging appear to be due to changes at both the receptor and post-receptor levels. Although many such observations have now been independently confirmed, disagreement over the extent and/or importance of receptor alterations exists in a number of cases. Receptors do not appear to change with age in certain systems, but only a few reports have actually been able to localize particular post-receptor alterations responsible for changes in response. This review attempts to catalogue studies in these areas which have been carried out to date, and discusses possible reasons for discrepancies as well as future research directions.

Effect of age on sensitivity to pain and brain opiate receptors.

Age-related differences in sensitivity to pain as induced by heat and electrical shock were seen among groups of rats; 2-3, 6-12, and 24 months of age. These are differences were at least partially obliterated by naloxone treatment, suggesting that changes may occur in the endogenous opioid system during aging. In contrast to higher pain thresholds in older animals, however, are decreased concentrations of opiate receptors in the frontal poles, striatum and hippocampus. Anterior cortex and amygdala exhibit a trend toward decreased concentration with increased age, but this is not significant. No age changes in binding affinity occur in any of the brain regions examined. Possible explanations for the apparent discrepancy between altered receptors and response include: higher endogenous opioid levels in aged rats, mediation of pain sensitivity by brain regions other than those examined, difficulties inherent in attempting to localize age changes at a single step in such a complex process, and possibly differential spinal pathways mediating the various types of pain.