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To determine whether inhaled silicon carbide whiskers (SiC) cause lung damage in rats, four groups (50 males/50 females each) of rats were exposed to air only or to one of three concentrations of SiC 6 hr/day, 5 days/week for 13 weeks. Half (25 males/25 females/group) were euthanized at the end of exposure, the remainder 26 weeks later. Mean concentrations were 0, 630, 1746, and 7276 SiC whiskers/ml (0.09, 3.93, 10.7, and 60.5 mg/m3). Although there were no concentration-related changes in body weight, clinical chemistry, or hematological data attributable to SiC, lung weights were increased in the high concentration exposure group at both euthanization times. In all whisker-exposed groups, after 13 weeks of exposure, the incidence of the following lung and lymph node lesions was higher than in controls: inflammatory lesions; bronchiolar, alveolar, and pleural wall thickening; focal pleural fibrosis in lung; and reactive lymphoid hyperplasia in bronchial and mediastinal lymph nodes. After 26 weeks of recovery, lung inflammatory lesions had decreased and fewer rats had enlarged lymph nodes, but the incidence of alveolar wall thickening, focal pleural wall thickening, and adenomatous hyperplasia of lung had increased further. Incidence and severity appeared to be dose-related. Therefore, until longer term studies are undertaken and it is established whether the above observed lesions will progress to more severe pathological entities, it is prudent to adopt stringent handling procedures for silicon carbide whiskers.

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The effects of magnesium deficiency in ovariectomized and estrogen-treated rats were examined in histological sections of bones and various soft tissues. The changes observed in the femora of intact rats deprived of magnesium for three weeks were: 1. a general increase in diaphyseal thickness, 2. the presence of localized fibrous or bony-like masses in subperiosteal and metaphyseal sites, and 3. the occurrence, although rare, of endosteal hyperplasia. In ovariectomized, magniesium-deprived animals, the incidence and location of fibrous masses were similar to that in the femora of magnesium-deficient intact rats; however, no increase in diaphyseal thickness was noted. Daily injections of 25 mug estradiol caused a reduction of the frequency of skeletal hyperplasia from 80% to 20%, as well as a reduction in femoral diaphyseal thickness. Estradiol hormone administration also brought about a marked alleviation of the dermal and neural manifestations of magnesium deficiency, but, at the same time, caused an exacerbation of renal calcinosis.

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Studies were carried out on the morphological and physiological effects of the binding of poly-L-lysine (polylysine; mol wt≊120,000) to the apical surface membrane of the toad bladder epithelium. Paired hemibladders were mounted in chambers and exposed to polylysine concentrations of 2, 8, or 80 µg/ml in the mucosal medium for periods of up to 2 hr. Radioautographs prepared after addition of(3)H-polylysine showed that the polymer was localized to the apical surface of the epithelium and in dense subapical masses in lysed cells. No significant morphological changes were seen in the epithelium by light or electron microscopy at polymer concentrations of 2 and 8 µg/ml. Exposure to 80 µg/ml lysed many epithelial cells, i.e., converted them to slightly swollen ghosts with pycnotic nuclei and empty cytoplasm, except for remnants of mitochondria and vesicular fragments of the endoplasmic reticulum. All of the superficial epithelial cells were lysed in stretched hemibladders. The plasma membranes of the lysed cells were uniformly thickened, and their intercellular attachments remained intact. In contracted hemibladders, lysed and normal-appearing cells were interspersed, and the number of lysed cells in the epithelium was proportional to the duration of exposure to high concentrations of the polycation. In parallel experiments, the effects of varying concentrations of polylysine on active Na(+) transport and osmotic flow of water were measured with and without vasopressin, aldosterone, or amphotericin B in the media. At a concentration of 2 µg/ml of polylysine in the mucosal bathing solutions, no change in the basal rate of Na(+) transport was seen, and the response to vasopressin was unimpaired. At a concentration of 8 µg/ml, there was a significant but small fall in electrical potential difference (PD) and in short-circuit current (SCC) and no interference with the response to vasopressin. At a concentration of 80 µg/ml, there was a rapid curvilinear fall in SCC to 54±4% of the baseline value and in PD to 21±3% of the baseline value in a 2-hr period. Simultaneous unidirectional isotope flux studies with(22)Na and(24)Na showed a more than twofold increase in the serosal to mucosal flux but no discrepancy between net flux and SCC. Despite the inhibitory action of the polymer, the stimulatory response in Na(+) transport to vasopressin, aldosterone, and amphotericin B was relatively preserved in that the percentage increase in SCC was the same in the polymer-treated and control hemibladders. The polycation produced a small but significant increase in osmotic water flow, and striking and irreversible inhibition of the water-flow response to vasopressin.