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Biomedical subjects

C A Heyneman

Publications and source records attributed to C A Heyneman.

4 recordsLinked to original sources

Role of the alveolar macrophage in the induction of pulmonary phospholipidosis by chlorphentermine. I. Drug and phospholipid levels.

In this study we have shown that the alveolar macrophage (AM) plays a major role in the induction of phospholipidosis in rat lung by chlorphentermine (CP). Rats were administered CP (30 mg/kg i.p., 5 days/week) for 1, 4 and 8 weeks and the levels of CP and total phospholipid were measured in whole lungs and in the AM fraction recovered from the lungs by pulmonary lavage. Lungs accumulate CP to a much greater extent than liver or kidney and show a marked increase in phospholipid content by 8 weeks. Drug treatment is accompanied by the recovery of an elevated number of AMs at all time points. The CP and phospholipid levels in AMs reach a peak at 4 weeks with little change beyond that time. Initially the phospholipidosis is localized largely in the AMs with the disorder developing in other compartments of the lungs with increasing treatment time. The AMs contribute 3% of the total pulmonary phospholipid in control rats. After 1 week of CP, 34% of the pulmonary phospholipid is in the AM fraction with this value being 21% after 8 weeks. The CP to phospholipid molar ratio is higher in AMs than whole lung at all three time points.

Animals

Role of the alveolar macrophage in the induction of pulmonary phospholipidosis by chlorphentermine. II. Drug uptake into cells in vitro.

This study was conducted to further assess the role of the alveolar macrophage in the induction of pulmonary phospholipidosis by the cationic amphiphilic drug, chlorphentermine (CP). Alveolar macrophages were collected from normal rats by pulmonary lavage, allowed to attach to glass cover slips and incubated with CP in vitro at 37 degrees C. The uptake of CP was measured using [14C]CP. Uptake is rapid, reaching equilibrium by 2 min resulting in the concentration of CP within the cells. The process is temperature-dependent being depressed markedly at 2 degrees C. Two components of uptake were identified. Below 0.2 mM CP, a carrier-mediated mechanism and diffusion are involved whereas, at concentrations above 0.2 mM, the carrier is saturated and diffusion predominates, with the intracellular binding of CP to membranes probably responsible for the striking sequestration. The carrier-mediated component obeys Michaelis-Menten kinetics, does not appear to require Na+ and is not affected by metabolic inhibitors. This is consistent with the concept that the process occurs by facilitated diffusion. Metabolism of CP does not play a role in the accumulation of the drug. The transport system is different from those involved in glucose, nucleoside or amino acid uptake. Total initial uptake was inhibited by the three cationic amphilic drugs tested, iprindole, chlorcyclizine and imipramine indicating that cationic amphiphilic drugs may share a common uptake system.

Animals

Chlorcyclizine--induced pulmonary phospholipidosis in rats.

Chlorcyclizine (CZ) was administered to rats (100 mg/kg, p.o.) for either 1 or 2 weeks (5 days per week). Controls were pair-fed and received deionized water vehicle for the same periods of time. The level of total phospholipid increased about 50% in the lungs after 1 week of CZ but did not increase further after 2 weeks of treatment. There was a time-dependent increase in the recovery of alveolar macrophages (AMs) from the lungs of the CZ-treated rats as well as in the phospholipid content of the cells. After 2 weeks of CZ, the AMs contained 5.6-fold more phospholipid than controls. The AM fraction showed a greater relative elevation in phospholipid at both time points than did the remainder of the lung tissue. The results illustrated the marked susceptibility of the AM to the disruption of phospholipid metabolism by CZ.

Animals

A 'water walkers' exercise program for the elderly.

Recent studies have shown that older people, stereotyped as weak, frail, and inactive, demonstrate an equal capacity to reap the physical and psychological benefits of recreational exercise. A low cost aquatic exercise program is proposed that is geared towards those persons who, because of their physical limitations, are unable to participate in the more traditional walking or low-impact aerobics programs currently available for seniors. A water-based program would allow these people to gain all the advantages of land-based exercise with out stress or strain on arthritic joints. In addition, the use of water walkers (a buoyancy device which attaches easily around the waist) would allow total freedom of movement without fear of deep water. Those with various levels of disability could, therefore, participate at their own pace. Two programs, including transportation, would be provided twice a week for 8 weeks each. An individual 45-minute session would consist of a warm-up period with gentle stretching, a cardiovascular segment, a cool-down period, strength-training, and a final stretching time. All exercises would be conducted with participants wearing the water walkers, allowing total immersion to the shoulder. Free to move about the pool, they would be encouraged to interact socially with one another. The results of the program would be determined by measuring range of motion, cardiovascular endurance, and strength before and after each 8-week session. Participants' level of self confidence and life satisfaction will be estimated and any psychological improvement will be documented.

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