Asbestos-induced lung injury in the sheep model: The initial alveolitis

In order to study the cellular and biochemical changes in early asbestosis, three groups of sheep were repeatedly exposed to intratracheal instillations of either saline (controls), low doses of UICC chrysotile asbestos (LD), or high doses of the fibers (HD) until an alveolitis was observed in all HD sheep during the twelfth month of exposure. All sheep were studied bimonthly by transbronchial lung biopsy (LB), bronchoalveolar lavage (BAL), pulmonary function tests (PFT), and chest roentgenograms (CXR). While LBs of the HD sheep demonstrated large accumulations of monocyte-macrophages in the alveolar and interstitial spaces, those of controls and LD sheep did not. In BAL, there was no difference in total and differential cell counts between groups, but the BAL lymphocyte proliferative capacity was clearly depressed in all asbestos-exposed sheep. In the BAL supernatant, total proteins (mainly albumin, beta + gamma globulins) and lactate dehydrogenase were significantly elevated in the HD group only. This alveolitis was associated with a fall in vital capacity, lung compliance, diffusing capacity, and arterial P_O2. Abnormalities on CXR appeared 3 months later. Thus, the cellular and biochemical features of early asbestosis are clearly distinct from those reported in idiopathic pulmonary fibrosis.     

The determinants of infant and child morbidity in Lagos,Nigeria

Analysis of the structure of real morbidity among children in Lagos, Nigeria, reveals that the leading diseases were of hygienic, nutritional and perinatal origin. These diseases were highly concentrated in infancy and early childhood; in the case of the former, the concentration was greater among boys than girls. During the 1970s, a decline is noticed in the frequency of infective and parasitic diseases particularly among male infants. Simultaneously, a slightly rising trend of diseases related to birth complications and perinatal nature afflicting predominantly early infancy occurred, off-setting, to some extent, the effect of the diminishing trend in infective diseases. The rising trend of perinatal diseases should be seen in conjunction with a likely increase in gravidity of women and the resultant increase of pregnancies and birth complications, which affected the health of the mother as well as that of the child.The findings seem to suggest that although both medical and non-medical factors contributed to the change in morbidity pattern in the decade 1968–1978, the role of factors of socio-economic nature was significant. The implication is that without socio-economic epidemiology, biomedical epidemiology could make a limited contribution to the reduction of morbidity.     

Effect of methylmercury and inorganic mercury on protein synthesis in mammalian cells

Effects of methylmercury and inorganic mercury on protein synthesis in several mammalian cells and cell-free systems were studied. Inorganic mercury showed about a 10 times stronger inhibitory effect on protein synthesis than methylmercury in the cell-free systems prepared from mouse glioma, Yoshida ascites sarcoma cells, and rabbit reticulocytes. Methylmercury inhibited protein in intact cells of Yoshida ascites sarcoma more strongly than inorganic mercury and exerted nearly the same inhibitory effect on protein synthesis in mouse glioma and rabbit reticulocytes as inorganic mercury.     

Distribution and binding of intratracheally instilled cadmium in rat lung

Retention, subcellular distribution, and the nature of binding of cadmium in lungs were studied following a single intratracheal instillation of cadmium. The clearance of intratracheally instilled cadmium from the lungs was very rapid during the initial periods of exposure and liver accumulated a maximum amount within 1 day. A low-molecular-weight cadmium-binding protein was isolated and characterized from lung cytosol. Cadmium administration increased metallothionein-like protein content but not sulfhydryls and zinc. The decrease in metallothionein at subsequent days of the exposure indicates the possibility of transport of this protein to some other target organs or the destruction of few cell types involved in providing protection against cadmium toxicity.     

Cytological shift in lymphocytes induced by cadmium in mice and rats

The hematological response as well as the clinical response such as retarded growth, polyuria, and proteinuria in cadmium poisoning was investigated in mice given a daily subcutaneous injection of sublethal doses of cadmium (below 2 mg Cd/kg) for 1 to 7 weeks and in rats exposed daily to an inhalation of cadmium oxide fumes (0.1 and 1.0 mg CdO/m³) for 4 weeks. Besides a usual tendency toward neutrophilia and lymphopenia in cadmium poisoning, a significant cytological shift of lymphocytes to large lymphocytes was found in the cadmium-treated mice and rats under extended cadmium exposure. This alteration in lymphocytes was observed earlier than anemia and the other responses. It was apparent already 1 week after initiation of cadmium injection and was amplified when the administration was further prolonged. This cytological shift also depended on the dose of cadmium (0.0625 to 2 mg Cd/kg) at week 1. The increase of large lymphocyte counts was accompanied by the decrease of small lymphocyte counts and by the increase in spleen weight. These findings in lymphocytes indicate that cadmium may affect the immune system directly or compensatorily. Differential counts of lymphocytes could be a useful clinical indicator for early detection of adverse effect of environmental and industrial exposure to cadmium.     

Ethnicity in the reported pain, emotional distress and requests of medical outpatients

Relationships of patients' ethnicity to their reported pain, emotional distress and requests were investigated. When patients aged over 60 years were compared. Italian-Americans were found to more frequently report pain than were Anglo-Americans; however, this difference was not replicated in the younger patients of Italian and Anglo backgrounds. In addition to patients' age, their sex also was found to mediate the relationship of ethnicity to the expression of pain. In particular, older female Italian-Americans were likely to report pain while, in contrast, older male Anglo-Americans were not. Age and sex may be important mediators of ethnic differences because older and female patients may carry on ethnic traditions more than do younger and male patients. Ethnicity was not found to be significantly related to emotional distress and requests.     

Alpha-difluoromethylornithine as a postcoitally effective antifertility agent in female rats

Intraperitoneal injection of alpha-difluoromethylornithine (DFMO) at a dose of 200 mg/kg, twice a day, during days 4-7 of pregnancy caused inhibition of embryogenesis in rats. These animals did not deliver any pups at term. However, there was no effect of DFMO on pregnant rats following treatment during day 1-3 of pregnancy. It was observed that DFMO completely abolished ornithine decarboxylase levels in the pregnant uterus. The action of DFMO appears to be due to the inhibition of putrescine and polyamines during a critical period of early embryo development. We suggest that this drug may act as a postcoitally effective antifertility agent in females.     

Identification of carcinogens by measurement of cell-mediated immunity: III. Immunity to asbestos-induced rat peritoneal mesothelioma

Antitumor cell-mediated immune (CMI) responses were detected in rats with asbestos (Canadian chrysotile B)-induced peritoneal mesotheliomas. The CMI was determined by in vitro lymphoid-cell cytotoxicity expressed by committed peripheral blood lymphoid cells (PBLC) obtained from the tumor-bearing animals toward cultured target cells of the tumors. Two apparently different target cell cultures which were developed from tumors of the same rat, one with epitheliod and the other with fibroblastic morphology, were lysed to the same degree by the sensitized PBLC. Specificity was observed for the PBLC reactivity as no cytotoxicity was expressed toward target cells derived from tumors of either ectodermal or entodermal origin. Nor were PBLC obtained from rats bearing tumors of these two tissue types capable of expressing injury to the mesothelioma target cells. These findings indicate that immune responsiveness developed to mesothelioma and suggest that such measurements might be useful for detecting environmental exposures to asbestos fibers.     

Wollastonite exposure and lung fibrosis

Wollastonite is a naturally occurring acicular or fibrous metasilicate used in ceramics and as a substitute for asbestos in some applications. Wollastonite fibers are rather similar in form, length, and diameter to amphibole asbestos fibers but mineralogically they are different. Dust measurements in both the Finnish limestone-wollastonite quarry and in the flotation plant yielded high concentrations of both total dust and respirable fibers in some operational stages. The clinical study comprised a total of 46 men who had been exposed to wollastonite at the quarry for at least 10 years. Three of the fifteen nonsmokers showed chronic bronchitis. Radiographs revealed slight lung fibrosis among fourteen men, and slight bilateral pleural thickening among thirteen men. Their sputum specimens were normal. Spirometry and nitrogen single breath tests indicated the possibility of small airways disease.     

The sensitivities of creatine and adenylate kinases to the neurotoxins acrylamide and methyl n-butyl ketone

It has recently been proposed that the similar multifocal axonopathies caused by several industrial toxins are due to the inhibition of metabolic enzymes with sensitive sulfhydryl groups. We find that the neurotoxins acrylamide and methyl n-butyl ketone in millimolar concentrations irreversibly inhibit rat brain and rabbit muscle creatine kinase and brain adenylate kinase. Brain creatine kinase was more sensitive to the toxins than was muscle creatine kinase or brain adenylate kinase. The chemically related but “nonneurotoxic” agents, N,N′-methylene bisacrylamide and methyl isobutyl ketone, were somewhat less effective than the known toxins. Dithiothreitol protected the enzymes against the toxins. However, differences in the effects of temperature and the protection by dithiothreitol indicated complex enzyme -toxin -dithiothreitol interaction. Protection by dithiothreitol does not necessarily implicate enzyme sulfhydryl groups or the site of toxin action. The lack of of cificity of toxin action and the concentrations of toxin required make it unlikely that metabolic enzyme inhibition alone accounts for hydrocarbon axonopathy.     

Corn oil-induced changes in the dorsal root ganglia of rats

The effects of corn oil on rat dorsal root ganglia (DRG) were examined by both light and electron microscopy. Rats were fed corn oil via intubation 5 days per week for 7 weeks. No apparent morphological lesion was observed in the DRG by means of light microscopic examination. However, various cytological changes were revealed by electron microscopy. The most prominent change was the extensive and severe edematous condition in the interstitial space. After 7 weeks of treatment, the interstitial space between neurons and nerve fibers was distended by proteinaceous edematous fluid and collagen fibers. Distention of the intercellular space between the ganglion neurons and their surrounding satellite cell sheaths also occurred. Proliferation of the supporting cells, especially the satellite cells and Schwann cells, producing long and complex networks of cellular processes in the distended interstitial space was also evident. It is believed that chronic ingestion of corn oil by rats has an adverse effect on the endothelial system leading to an increased fluid permeability and edematous condition.     

Reproductive inhibition caused by the anti-inflammatory analgesic benzydamine in the rat

The anti-inflammatory analgesic benzydamine was given to pregnant rats from Day 15 of gestation to Day 21 of lactation and from Days 6 to 15 of gestation at daily oral doses of 50, 100, or 200 mg/kg. The dams were observed to assess maternal toxicity, viability, growth, and symptomatology throughout the two studies. The offspring from the first study were observed for litter size, weight, still births, and subsequent development from birth to weaning. In the second study, all dams were sacrificed on Day 20 and examined for parameters of fecundity, embryotoxicity, and teratogenicity. Dams given 200 mg benzydamine/kg during late gestation and lactation exhibited signs of maternal toxicity and a 35% mortality. Significant decreases in litter size, weight, live births of either sex, and progeny body weights were noted at birth from these dams. Subsequently, body weights during lactation were depressed while progeny mortality was increased. Dams given 50 or 100 mg/kg during late gestation and lactation were not adversely affected, but progeny body weights (predominantly males) were significantly decreased. Dams given up to 200 mg benzydamine/kg during the “critical period of organogenesis” displayed no signs of maternal toxicity, and no adverse reproductive or teratogenic effects were detected. Thus the demonstrated inhibition of reproductive performance by benzydamine appears to be due to an increase in maternal toxicity during late gestation and lactation. This difference, coupled with a greater adverse effect on male offspring during lactation, may suggest either a change in the pathway of benzydamine metabolism or a piperazine-like selectivity after repetative doses.     

Amino acid changes and pulmonary response of rats to silica dust

The effect of intratracheal injection of quartz on the free amino acids of lung, serum, and liver and the bound amino acids of lung was studied in rats, at intervals preceding and following the formation of collagen. The studies revealed that amino acid metabolism is significantly altered in silicotic rat lung. Changes in the body pool of amino acids seem to be related to both collagen and noncollagen formation in silicotic lung. It appears that some of the amino acid residues for collagen formation in lung in response to silica exposure are made available by the in situ formation from available precursors, while others are contributed by other organs, especially liver. A central role for glutamic acid metabolism in the genesis of pulmonary fibrosis is discussed.     

Biodegradability test results related to quality and quantity of the inoculum

For a series of different biodegradation test methods the biodegradation curves are simulated by computer. Simulations are performed on the basis of Monod growth kinetics corrected for cell decay. The possibility of discriminating between growth rates is related to variability of the inoculum quality and quantity. It is concluded that the variability of the inoculum masks all other information. The Repetitive Die Away test, however, offers a good opportunity to obtain information on growth rates that is highly relevant to environmental assessment. The conclusions derived from the computer-simulated curves are confirmed by experimental data.     

Protective effects of vitamin E on methylmercury toxicity in the dorsal root ganglia

The protective potential of Vitamin E against methylmercury neurotoxicity was investigated by means of both light and electron microscopy. Rats were treated with a daily dosage of methylmercury (2.0 mg McHg/kg body wt), Vitamin E (50 mg Vit. E/kg body wt), both methylmercury and Vitamin E, or saline solution for 8 weeks. All animals were sacrificed by intracardial perfusion of fixative and the dorsal root ganglia (L₁-L₄) (DRG) were sampled for examination. No remarkable pathological changes were observed in animals treated with Vit. E alone. McHg-treated animals showed toxic neurological signs at 8 weeks of exposure. Both light and electron microscopy demonstrated morphological changes in the neuronal cell bodies (extensive lysosomal accumulation and destruction of Nissl substance—rough endoplasmic reticulum and polyribosomal clusters) and in the dorsal root fibers (axoplasmic degradation and myelin sheath degeneration). In contrast, the McHg/Vit. E-treated animals displayed no observable neurological signs after the same duration of McHg exposure. Pathological examination revealed full protection of the DRG neurons which showed no significant degenerative changes as did those observed in McHg-alone animals. Degenerative changes, however, were still observed in the dorsal root fibers, showing moderate changes (lysosomal and axoplasmic debris accumulation) in some axons, particularly at the regions of the Nodes of Ranvier, and destruction of the myelin sheaths. It is shown in this investigation that Vitamin E can offer significant protection against methylmercury toxicity. Under our present experimental conditions, the protective effectiveness appears to be neuronal cell body > axoplasm > myelin sheaths.     

Cytopathology of the brain and retina of embryonic surf smelt (Hypomesus pretiosus) exposed to crude oil

In laboratory experiments, surf smelt (Hypomesus pretiosus) embryos were exposed to 54 or 113 ppb of the seawater-accommodated fraction (SWAF) of Cook Inlet crude oil (CICO) for 3 hr per day, beginning 6 days after fertilization. Embryos 21 and 27 days old (just prior to hatching) exposed to CICO were examined for morphological abnormalities. The only tissues that showed morphological changes in both the 21- and 27-day-old CICO-exposed smelt were the forebrain and the neuronal layer of the retina: both contained numerous necrotic neurons. The retinal receptor cells appeared normal in 21-day-old exposed smelt; in contrast, in 27-day-old treated embryos the ellipsoid and myoid regions of the receptor cell inner segments were severely damaged. Further impact from the SWAF of CICO on developing smelt was indicated by a lower hatching success: approximately 10% in the exposed groups as compared to 50% in the controls.     

Effects of selenium on mercury-induced renal lesions and on subcellular mercury distribution

The effects of selenite on the renal tubular lesion caused by mercuric chloride were studied by electron microscopy using male rats injected with HgCl₂ and/or Na₂SeO₃. The protective effect of selenite on mercury-induced renal injuries was confirmed both in proximal tubular cells and in glomerulus. Mercury specifically deposited in lysosomes in proximal tubular cells of rats which received either mercury alone or mercury plus selenite, although the density of fine gold grains, which revealed the mercury deposits, appeared to be higher in the rats treated with mercury alone than in those administered mercury and selenite. These observations by electron microscopic histochemistry were consistent with the analytical data for mercury in the kidneys. The results suggest that the reduction of renal mercury toxicity by selenite should be ascribed not to the change in subcellular mercury localization but to the decrease in the level of mercury in kidneys.     

Ultrastructural studies on the cytotoxic effects of mercuric chloride on mouse glioma

Cytotoxic effects of mercuric chloride on cultured mammalian cells were studied by light and electron microscopy. Cell proliferation of mouse glioma was completely suppressed by treatment with 5 × 10⁻⁵ mercuric chloride. The mitotic index remained at the control level for 4 hr after treatment but decreased afterward. The amount of mercuric mercury bound to the cells increased markedly above 2 × 10⁻⁵ mercuric chloride. Electron microscopic examination revealed many kinds of changes of organelles in cells exposed to 5 × 10⁻⁵ mercuric chloride for 4 hr: Nuclei were transformed into pyknotic and irregular shapes; mitochondria lost their normal cristae and abnormal electron dense-areas were present within the matrix; polyribosomes were dispersed. Numerous electron-dense granules and vacuolations were seen in the cytoplasm, especially around the Golgi region. However, microtubules were still evident, although the amount seemed to decrease compared with control cells. Thus, the inhibition of growth by mercuric chloride may be ascribed to the degenerative changes which occur in many organelles.     

The detection of some N-nitrosamines in the water cycle

Aqueous samples, aggregated over a week, were taken from the inlets and outlets of three sewage treatment works. Samples were also collected from a cutting-fluid recovery plant whose contents are periodically discharged into the water system feeding one of the sewage works. The samples were subjected to solvent extraction and the extracts examined for the presence of volatile nitrosamines using gas chromatography. Extracts were also examined for N-nitrosodiethanolamine after preparing a volatile derivative of this compound. Detection and quantitation of the nitrosamines were by chemiluminescent measurements, and in some instances extracts were additionally examined by mass spectrometry as confirmation. All samples contained one or more of the following nitrosamines: N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosomorpholine, and N-nitrosodiethanolamine. The highest levels (<100 μg/liter) were found in the cutting-fluid recovery plant, which also contained N-nitroso-5-methyl-1, 3-oxazolidine. The highest level in the other samples was 1 μg/liter N-nitrosodiethanolamine.