[Normoxic sustained hypercapnia in the SPF rat: hematology and electrolyte status. Influence on the oxygen status (author's transl)].
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Biomedical subjects
Publications and source records attributed to P Duprat.
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The acute effects of two industrial substances were studied in mice, rats, rabbits and guinea pigs: - lethal concentration 50 (L.D. 50) in mice and rats after intraperitoneal and oral administration; - investigation of cell growth inhibition (Hela cells), I.D.50 = inhibitory dose 50%; - neuropharmacological effects Histopathological investigations and biochemical analysis pointed out hepatic and renal damages; besides hematological disturbances were found. Both products had mild irritant effects on rabbits skin and eyes. They produced skin sensitization in guinea pigs.
Rabbits have been epicutaneously exposed to pure hexachlorobutadiene (0.25; 0.50; 0.75 and 1.00 ml/kg) during 8 hrs. This solvent was completely absorbed; some animals died within 24 hrs and others a few days later. The LD50 is 0.72 ml/kg (Bliss' method). Hexachlorobutadiene induced in situ cutaneous necrosis and its absorption induced systemic damage (fatty liver degeneration and epithelial necrotizing nephritis). These lesions are reversible. The present results confirm the toxicological profile of this solvent, previously established by the intraperitoneal and oral routes: hexachlorobutadiene is the most nephrotoxic aliphatic chlorinated hydrocarbon.
Rats were exposed 24 hours a day to carbon dioxide, 8 +/- 1%, during 2 and 4 weeks under normoxic conditions (21% oxygen). On the last day, blood was taken from the abdominal aorta under anesthesia. Leukocyte and erythrocyte counts, hemoglobin concentration, and mean cell volume were electronically measured. Hematocit and Wintrobe indexes were calculated. Leukocyte differential counts and peroxidase activity were determined on blood smears. After 4 weeks of hypercapnia, a slight decrease of neutrophilic granulocytes was observed. In mature polymorphs, peroxidase activity (cytochemically demonstrated) simultaneously decreased. Erythrocyte counts and mean cell volume remained unchanged. The most important hematological disturbance was an hemoglobin concentration drop. Consequently, it was concluded that an hypochromic anemia characterized the permanent normoxic hypercapnia in rats.
Forty-two cases of contact sensitivity to N-isopropyl-N'-phenylparaphenylenediamine (IPPD), an amine antiozonant used in rubber manufacture, were collated from several firms and plants dealing with tyres. Ten motor car tyres manufactured by eight different firms all induce sensitivity reactions in seven subjects allergic to IPPD. Clinical cross-reaction tests show that 100% of the subjects sensitive to IPPD are also sensitive to N-phenyl-N'-cyclohexy-paraphenylenediamine (CPPD), another amine antiozonant, and 37% to paraphenylenediamine (PPD). The various types of tyres were analyzed by gas chromatography and then by infra-red and thin-layer chromatography where necessary. None of the 12 tyres examined was found to be free from aromatic amines. Test reactions carried out with various automobile accessories on subjects allergic to IPPD in tyres gave positive results precisely in those cases where the articles contained IPPD. The authors then studied occupational sensitivity to N-dimethyl-1,3 butyl-N'-phenylparaphenylenediamine (DMPPD), a rubber antiozonant purported to be non-sensitizing and marketed in the United States. The The DMPPD tests were positive for all the IPPD-allergic patients tested; there is no doubt as to the allergenic nature of DMPPD. The irritant and sensitizing potentials of the four amines in question were tested in laboratory animals: PPD proved to be the most allergenic product, IPPD the least allergenic, and DMPPD and CPPD seem to give identical results. All these products produce positive cross-reactions in varying degrees of severity.
Organic photopolymerizable resins increasingly used in printing make it possible to produce flexible, lighter plates. A certain number of skin lesions and general symptoms appeared upon manipulation of plates made by the Letterflex process. In the workshop where this study was carried out, 12 out of 15 people suffered various degrees of skin lesions. The epicutaneous tests and biopsies performed indicate an allergic type reaction to one of the resin's constituents, polythiol. Experiments with animals confirm the strong allergenicity of this compound.
The diallylglycol carbonate monomer causes dermatitis due to irritation in the optical industry. Cutaneous intolerance may effect as many as 70% of the exposed persons employed. Almost all control subjects who where patch-tested showed irritation at a 2% concentration. The histological effects were an acute oedema with inflammation of the papillary dermis, and diapedesis of neutrophil polymorphonuclear leukocytes. Experiments on animals confirmed the irritant nature of the product; in the rabbit, a single application produced irritation, but to a lesser degree than in humans. Tests for possible sensitizing effects in the guinea pig have given negative results. Chemical analysis of the monomer revealed the presence of diallyl carbonate and acrolein. Allyl alcohol was detected in only one case. Patch tests were carried out in a group of control subjects with acrolein, diallyl carbonate and allyl alcohol. The histological appearance of the lesions caused by acrolein was quite different from that due to diallyglycol carbonate. It is probable that the irritant is the diallylglycol carbonate monomer itself.
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Porcine growth hormone was administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/d for 14 weeks, markedly elevating serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. This was accompanied by a significant increase in body weight gain and kidney weights in both male and female dogs. The increase in kidney weight (6 to 54%) was slightly greater than the increase in body weight (6 to 40%). By light microscopy, glomerular deposits, mesangial thickening, and very slight cellular infiltration in glomeruli were seen in mid- and high-dose groups. Based on morphometric evaluation, there was an increase in the renal glomerular area, which was statistically significant (p < or = 0.05) in the mid- and high-dose males and in the high-dose females. This was associated with a statistically significant (p < or = 0.05) increase in the number of total glomerular cells in the mid- and high-dose males. By transmission electron microscopy, thickening of the glomerular basal lamina and diffuse increase of the mesangial matrix were observed in both male and female dogs in the mid- and high-dose groups. Immunohistochemical reactions were negative for IgG, IgM, and C3. The morphological changes in the kidney of dogs resemble the diffuse glomerulosclerosis described in human diabetic nephropathy.
The direct 5-lipoxygenase inhibitor L-739,010 was administered at a dose of 60 mg/kg/day per os to beagle dogs for 15 days. Histopathological examination of gallbladders from treated dogs showed epithelial vacuolation and submucosal infiltration by foamy macrophages that were positive for lipids in Sudan Black-and/or Oil Red O-stained sections. Scanning electron microscopic examination of gallbladder mucosa showed thickening of epithelial folds and multifocal epithelial membrane disruptions. Transmission electron microscopy confirmed these findings and showed mucosal epithelial cell lipid droplet accumulation and submucosal infiltration of macrophages filled with lipid droplets, myelin figures, heterophagosomes, and cholesterol clefts. These changes resembled those reportedly seen in the human gallbladder with cholesterolosis and/or chronic cholecystitis.
Growth hormone (GH) synthesis and release from the pituitary is regulated by hypothalamic releasing hormone, insulin-like growth factor-1 (IGF-1), and somatostatin. However, the potential effects of pharmacological doses of exogenous GH on the pituitary are not well studied. To determine the potential chronic effects of exogenous GH on pituitary morphology in dogs, porcine GH (pGH) was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served as the vehicle control. The pituitaries from all dogs were weighed and fixed in appropriate fixatives for light and electron microscopic examination; in addition, cells of the pars distalis were quantitated by a point counting method following immunostaining to identify cells containing GH, prolactin (PRL), and adrenocorticotrophic (ACTH) hormones. Administration of pGH resulted in a statistically significant (p < or = 0.05) increased pituitary weight through the high dose. By light microscopy (LM), hypertrophy of pars distalis cells was evident in mid- and high-dose female dogs. The pituitaries of dogs given the lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM findings. In addition, transmission electron microscopic (TEM) examination of the pituitary gland of high-dose demonstrated, in both sexes, pituitary cells with variably dilated rough endoplasmic reticulum and decreased numbers of secretory granules; some of these cells reacted positively to GH immunostaining. Quantitative analysis of the pituitary gland of high-dose males and females showed an increase in the absolute volume of all cell populations studied: GH-, PRL-, and ACTH-positive cells. Based on the LM and TEM findings, the increased volume of the cell populations studied is likely related to cellular hypertrophy. The expected elevation in serum GH levels following repeated administration of pGH and an associated elevation in serum IGF-1 levels resulted in morphologic changes in the pituitary gland of dogs given high doses (> or = 0.1 IU/kg/day) of pGH; these observations differed from the reported findings in pituitaries of transgenic mice secreting large quantities of bovine GH.
Administration of growth hormone (GH) results in increased body weight gain in dogs. Increased body weight gain is believed to be a result of the trophic effect of GH on the musculoskeletal system. However, edema is one of the side effects described in man following exogenous GH administration. Thus, the objective of this study was to determine if the expected increased weight gain in GH-treated dogs is a result of increased muscle mass. Porcine growth hormone (pGH), administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/day for 14 wk, resulted in elevated serum GH and insulin-like growth factor-1 (IGF-1) levels (see accompanying paper, Prahalada et al). This was associated with a significant increase in body weight gain and weights of the cranial tibialis muscle in both male and female dogs. The increased muscle mass likely contributed to the significant increase in body weight gain seen in both sexes. Quantitative analysis of skeletal muscle sections stained for ATPase activity showed increases in type I (slow twitch) and type II (fast twitch) myofiber sizes in mid- and high-dose males and in high-dose females. The ratio of type I and type II muscle fibers remained unchanged. Hypertrophic myofibers were enlarged but had a normal histologic and ultrastructural organization when observed by light and transmission electron microscopy. The results of this study have demonstrated that increased muscle mass in pGH-treated dogs is related to hypertrophy of muscle fibers and not due to edema. Exogenous GH administration has an anabolic effect on skeletal muscle in dogs.
This is a study on the irritant capacity of two isocyanates (T. D. I. Toluene diisocyanate and M. D. I. diphenyl methane diisocyanate). The experiment was carried out on the hide and ocular mucous membrane of albino rabbits, using Draize method as well as the method for appraising cosmetics. An histopathological examination of the evolution of the lesions was then achieved together with a study on the delayed allergenic capacity. This study was carried out on albino guinea-pig hides using Kligman and Magnusson technique. In these experimental conditions, the conclusions were the following:--on rabbit hide, T. D. I. is a medium irritant, more caustic than M. D. I.,--on ocular mucous membrane, M. D. I. is a mild irritant; T. D. I. a strong one,--on guinea-pig hide, T. D. I. and M. D. I. may induce cutaneous sensitivity similar to contact allergy. Their allergenic capacity is long lasting but varies according to the allergen concentration.