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Biomedical subjects

M J Reasor

Publications and source records attributed to M J Reasor.

At least 73 records · Page 4Linked to original sources
PubMed1983

Chlorphentermine-induced alterations in pulmonary phospholipid content in rats.

Daily, intraperitoneal administration of the anorectic drug chlorphentermine (30 mg/kg) for 5 days to rats significantly increased phosphatidylcholine and total phospholipid content after 1 week and reached a maximal level 4 weeks after treatment in whole lung tissue (unlavaged lungs) and in sessile tissue in which alveolar lipids and macrophages were removed by pulmonary lavage (lavaged lungs). In lavaged lung, a significant rise in the content of sphingomyelin, phosphatidylserine plus phosphatidylinositol component, and phosphatidylethanolamine plus phosphatidylglycerol fraction occurred after 2 weeks, remained at this increased level for 4 weeks, and was followed by a return to control amounts after 5 weeks. In unlavaged lung, the chlorphentermine-induced elevation in sphingomyelin content seen after 1 week persisted at this same significant level even 5 weeks after treatment. Regardless of experimental duration, pulmonary glycogen levels were not altered markedly by chlorphentermine in unlavaged or lavaged tissue. Phenobarbital (30 mg/kg) did not markedly alter pulmonary glycogen and phospholipid component levels. Simultaneous phenobarbital and anorectic drug administration prevented the chlorphentermine-induced rise in total phospholipid, sphingomyelin, and phosphatidylcholine in unlavaged lung without a change in glycogen. A 7-day withdrawal from chlorphentermine treatment in rats previously injected with drug for 2 weeks resulted in a return to control in the levels of sphingomyelin, phosphatidylcholine, and total phospholipid in unlavaged lung. Extension of withdrawal from treatment for 2 weeks produced a significant decrease in all phospholipid components below control values, suggesting that a possible imbalance in synthetic and catabolic activity may persist after drug removal. The concentration of lung glycogen was not altered significantly by chlorphentermine treatment or withdrawal from drug administration. Our results indicate that the chlorphentermine-induced rise in phospholipid components was time-dependent in lavaged and unlavaged lungs, and the increase in phosphatidylcholine occurred independently of a change in glycogen. In addition, the present study shows that the chlorphentermine-induced changes in phospholipid levels are reversible and almost completely prevented by phenobarbital.

Animals↗
PubMed1983

Chlorphentermine-induced alterations in the lungs of vitamin E-deficient and -supplemented rats: quantitative ultrastructural analysis of Type II Cell response.

Response of alveolar Type II (T-II) cells of male Sprague-Dawley weanling rats maintained on vitamin E (VE)-deficient and -supplemented diets to chlorphentermine (CP) treatment was evaluated. Ultrastructural and quantitative procedures were used to assess the T-II cell-drug interaction. Subjective examination of photomicrographs revealed numerous disrupted surfactant lamellar bodies in the CP-treated animals, as compared to fewer in controls. In addition, an unusual amorphous material was associated with these cells in drug-treated animals. Quantitative assessment confirmed the above subjective impression and revealed an increase in the size of T-II cells in treated rats. Morphometric evaluation showed that CP treatment significantly altered the volume density of cytoplasm, mitochondria, and rough endoplasmic reticulum (RER). Furthermore, a significant interaction between the diet and treatment with respect to volume fractions of mitochondria, RER, and Golgi complex was observed. The present study indicates that cytoplasmic components in T-II cells are altered as a result of CP treatment and that VE status of the animals influences the nature and extent of these alterations.

Animals↗
PubMed1983

Chlorphentermine-induced neonatal and maternal pulmonary phospholipidosis in rats.

Pregnant rats were treated on Days 16-20 of pregnancy with 30 mg/kg chlorphentermine hydrochloride (CP) or an equal volume of 0.9% NaCl. Females delivered on Day 21 and neonates were examined 12 hr postpartum. Electron micrographs showed the CP neonates to have lamellar inclusions, characteristic of drug-induced phospholipidosis in Type I and Type II cells, macrophages, and nonciliated bronchiolar epithelial cells of the lung. These inclusions were either unicentric, multicentric, or consisted of whorls of membranous material. The content of total phospholipids was increased in neonatal lung as a result of CP treatment. A decrease in the percentage of total phospholipid present as phosphatidylinositol plus phosphatidylserine and an increase in the content of disaturated phosphatidylcholine were found in neonatal lung as a result of maternal chlorphentermine treatment. In maternal lung, increases were seen in the content of total phospholipids, total phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylinositol plus phosphatidylserine. A decrease in the percentage of sphingomyelin was also found. The results of this study indicate that following prepartum maternal administration of CP morphological changes are accompanied by biochemical alterations which are consistent with the induction of phospholipidosis as observed in neonatal lung. These biochemical changes were different than those associated with the induction of this disorder in the maternal lung.

Animals↗
PubMed1983

Chlorphentermine-induced alterations in the lungs of vitamin E-deficient and supplemented rats: 1. Biochemical and morphometric analysis of the pulmonary response.

Male Sprague-Dawley rats were maintained on diets containing 0.60, or 300 ppm vitamin E (VE) for 9 weeks with chlorphentermine (CP) or saline vehicle (SV) treatments administered over the last 3 weeks (20 mg CP/kg for one week and 30 mg CP/kg for subsequent 2 weeks or equivalent volume of saline vehicle). Spontaneous erythrocyte hemolysis averaged 68% for VE-deficient (0 ppm) and less than 9% for VE-supplemented (60 and 300 ppm) animals prior to saline and CP treatments. These values were not changed significantly by vehicle or drug administration. The lung-to-body weight ratios nearly doubled and the total lung phospholipid levels increased equivalently (three- to fourfold) in all three CP-treated VE groups as compared to corresponding SV controls. The levels of thiobarbituric acid-reactive material (TBA-RM), an index of lipid peroxidation, was increased in the lung tissue above SV controls in all dietary groups with the deficient group being the highest. There was no difference in the TBA-RM values of 60 and 300 ppm groups within each group. Quantitative morphometric analysis revealed that in the VE-supplemented groups, CP treatment caused a significant increase in the number of alveolar macrophage foam cells (FC) with a slight increase in the volume density of surfactant-like material (SLM). By comparison, there were fewer FCs but a larger quantity of SLM in the VE-deficient group. The results suggest that VE deficiency modifies the pulmonary response to CP resulting in lipid peroxidation-induced FC disintegration and the accumulation of SLM.

Animals↗
PubMed1982

Neonatal toxicity in rats following in utero exposure to chlorphentermine or phentermine.

The administration of chlorphentermine (30 mg/kg) to pregnant rats during the last 5 days of gestation resulted in the development of a phospholipidosis in the lungs of the dams. The disorder developed in utero, as the phospholipidosis was evident in the lungs of the neonates when examined at 12 h postpartum. In contrast, a phospholipidosis was not observed in the lungs of the dams or neonates following phentermine treatment (30 mg/kg). Concurrently, neonates of the chlorphentermine-treated dams displayed a significant decrease in body weight in comparison to controls. Between 16 h and 24 h postpartum, 83% of the neonates of chlorphentermine-treated dams died. Cross-fostering and starvation experiments revealed that the lethality was not due to aberrant maternal behavior by the chlorphentermine-treated dams or malnutrition of the neonates. Histological examinations revealed endothelial and septal alterations in the lungs of neonates from chlorphentermine-treated dams. No signs of toxicity, as evidenced by the maintenance of body weight, or lethality were observed in the neonates of the phentermine-treated dams.

Animals↗
PubMed1982

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↗
PubMed1982

Multinucleation in alveolar macrophages from rats treated with chlorphentermine.

When rats were treated with chlorphentermine, a cationic amphiphilic drug, a phospholipid storage disorder developed in alveolar macrophages, the severity of which was directly proportional to the duration of treatment over a 4-week period. Concomitantly, a progressively greater percentage of the cells became multinucleated such that, after 4 weeks of drug treatment, 18 per cent of the cells contained more than one nucleus. Greater than 99 per cent of the macrophages from control rats had on nucleus per cell. Associated with the multinucleation was an increase in the DNA, RNA, and protein content of the macrophages and increases in the RNA to DNA and protein to RNA ratios relative to cells from untreated rats. Centrifugal elutriation was employed as a means to study the multinucleation as a function of increasing cell size. At each of the 4 weekly intervals studied, the percentage of cells with two or more nuclei increased as the cells became larger. An increase in multinucleation was also found in cells of any given size range as the time of treatment increased. Possible mechanisms responsible for the multinucleation phenomenon are discussed.

Animals↗
PubMed1981

Drug-induced lipidosis and the alveolar macrophage.

The alveolar macrophage is the principal component of the defense mechanisms of the lung. As a result, alterations in its function can predispose the host organism to pulmonary disease or damage. This cell shows toxic responses to a wide variety of chemicals which are delivered to the lungs by either inhalation or via the systemic circulation. In this regard, this review will focus on the effects of a group of cationic amphiphilic drugs which when administered to humans and animals causes a lysosomal storage disorder of lipids, principally phospholipids, in alveolar macrophages. The susceptibility to the disorder is species-dependent and can be induced in fetal, neonatal and adult animals. Evidence exists that the accumulation of lipids within the cells occurs as a result of an impairment in lipid catabolism, however, not all of the available data are consistent with this theory. In light of this, other mechanisms to explain the etiology of this lipidosis are discussed. Associated with the increase in lipid content within the cell, striking morphological, biochemical and functional changes occur to the alveolar macrophage. Available data indicate that afflicted cells have an increased phagocytic activity and exhibit enhanced killing of one strain of bacteria. While these data suggest an enhancement in certain cellular functions, inadequate information presently exists to allow conclusions to be drawn concerning the consequences of this disorder.

Animals↗
PubMed1981

Extracellular alkaline phosphatase from alveolar secretions of patients with pulmonary alveolar proteinosis.

Alkaline phosphatases in alveolar secretions from the lungs of patients with pulmonary alveolar proteinosis have been studied. A soluble form of alkaline phosphatase was isolated from the secretions and characterized. The extracellular enzyme had a pH optimum at 9.95; was stimulated by Mg2+, Ni2+, and Mn2+; was inhibited by Zn2+, Be2+, Cu2+, and low concentrations (8 mM) of L-homoarginine and imidazole; and was heat-stable at 55 degrees C. The soluble phosphatase existed primarily as a high molecular weight complex (excluded from Sepharose 4B) and could be dispersed into low molecular weight forms (205 000--285 000) by treatment with n-butanol. Following butanol treatment, the thermostability of the enzyme was markedly decreased but the kinetic properties such as the Km values, activation energies, and responses to various inhibitors were unchanged. The alkaline phosphatase may originate from unusual type 2 cells present in the alveoli of patients with pulmonary alveolar proteinosis.

Alkaline Phosphatase↗
PubMed1981

Iprindole-induced phospholipidosis in rat alveolar macrophages: alterations in oxygen consumption and release of oxidants.

Rats chronically treated with the cationic amphipilic drug iprindole developed a phospholipid storage disorder in their pulmonary alveolar macrophages (AMs). AMs from these iprindole-treated rats (IP-AMs) were compared to AMs from control rats (C-AMs) regarding oxygen consumption and the release of two reactive oxygen species, superoxide anion and hydrogen peroxide. Responses of C-AMs and IP-AMs were compared at rest and when stimulated by unopsonized or opsonized zymosan. Opsonization was not necessary in order to induce respiratory burst-associated phenomena in either cell type; in fact in all cases, for given cell type responses to unopsonized zymosan were virtually identical to those of opsonized zymosan. When at rest, IP-AMs consumed oxygen at a rate nearly identical to that of C-AMs. When stimulated with zymosan particles, IP-AMs consumed more oxygen than controls. However, when superoxide anion and hydrogen peroxide, two products of the respiratory burst were measured, IP-AMs released less of these species than C-AMs when at rest and when particle stimulated. Despite the lower total release of these species by the IP-AMs, the zymosan-induced release (stimulated minus resting levels) was greater for these cells than C-AMs. Therefore, the IP-AMs were found to be more responsive to the zymosan particle than C-AMs. The results indicate marked changes in the release of reactive oxygen species from the AMs following induction of phospholipidosis.

Animals↗
PubMed1981

Soluble protein synthesis in the neural retina during lens regeneration.

Lens regeneration in newts involves transformation of pigmented dorsal iris epithelial cells into lens cells. This process is somehow stimulated by the neural retina. In the present study, soluble proteins and their synthesis were analyzed in normal neural retina and in neural retina 12 days after lentectomy by means of disc and slab gel electrophoresis. Electrophoretic analysis revealed 16 prominent polypeptides (M.W. 18,500 to 185,000 daltons). The electrophoretic banding pattern of the neural retina was similar in normal eyes and in eyes 12 days after lentectomy. To determine which of these bands were being synthesized. 3H-leucine or 35S-methionine was injected prior to tissue preparation for electrophoresis. About 12 bands were found to be radioactive, again no major difference was seen in the radioactivity pattern of soluble proteins obtained from normal and lentectomized eyes. Since no major differences, were observed, the present results suggest that the neural retinal factor, if a soluble protein, is not a new protein but is present in normal retina.

Animals↗