Pathological lesions in larvae hatched from ovigerous females ofChasmagnathus granulata (Decapoda,Brachyura) exposed to cadmium

Morphological abnormalities were noted in larvae hatched from ovigerous females of the estuarine crabChasmagnathus granulata, exposed to 1 and 15 mg/l of cadmium during the egg incubation period. The highest concentration produced a significant incidence of hydropsy, atrophy of dorsal spine, pleon and pereiopods as well as enhancement of pigmentation. Some possible causes of these results are discussed and compared with the effects caused by other pollutants on the same species.     

The action of various vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryo calvariae

Summary Chick embryos from vitamin D-deficient hens given physiological doses of 1,25-dihydroxyvitamin D₃ or 24,25-dihydroxyvitamin D₃ or both become severely hypocalcemic, hyperphosphatemic and fail to hatch as compared to those derived from hens given 25-hydroxyvitamin D₃ or 24,25-difluoro-25-hydroxyvitamin D₃. Calvariae from the former contain less mineral and on incubation in vitro produce significantly lower calcium and higher phosphate concentration in the medium than do the calvariae derived from the embryos of hens supported on 25-hydroxyvitamin D₃ or 24,24-difluoro-25-hydroxyvitamin D₃.     

Neutrophilic granulocytosis following lead acetate in female mice

Summary Lead induces an abrupt neutrophilic granulocytosis with the peak response detected 4 days after treatment. Using the incorporation of tritiated thymidine as an index of neutrophil production, autoradiographic analysis revealed that only about 16% of the total neutrophil increase is associated with a stimulatory effect on production. The remainder of the increase appears to be linked to the panhistotoxic action of lead, promoting migration of neutrophils from reserve sites in the wake of tissue damage.     

Regional brain [Met]-enkephalin in alcohol-preferring and non-alcohol-preferring inbred strains of mice

Summary Scrutiny of the data from these studies reveals that the C58/J alcohol-preferring mice have significantly lower baseline methionine-enkephalin levels in both the corpus striatum and hypothalamus compared to C3H/CHRGL/2 non-alcohol-preferring mice. In other brain regions in these two strains, specifically, pituitary, amygdala, midbrain, and hippocampus, analysis of methionine-enkephalin levels did not show any significant differences. This suggests that the hypothalamus may indeed be a specific locus involved in the regulation of alcohol intake, via the molecular interaction between neuroamines, opioid peptides, as they are influenced by genetics and environment.     

Increased melatonin levels after hemorrhagic shock in male and female C3H/HeN mice

Although hemorrhagic shock leads to significant alterations of several hormones, e.g. ACTH, corticosterone and -endorphin, it is not known whether plasma melatonin levels are affected under this condition and if so, whether the effects are comparable in males and females. Using a radioimmunoassay, it was found that plasma melatonin levels were significantly increased in male and proestrus female C3H/HeN mice immediately after hemorrhagic shock. However, in male mice, by two hours after hemorrhage and resuscitation, plasma melatonin returned to levels comparable to those seen in control and sham-operated animals. Proestrus female mice, on the other hand, showed significantly increased plasma melatonin levels at two hours after surgery when compared to unoperated control animals. Although the significance and biological role of the transient increased plasma melatonin levels after hemorrhagic shock remain to be determined, it appears that the pineal gland and/or an extrapineal source of melatonin, of both male and proestrus female mice responds to severe hypotension by increased release of melatonin.     

Evidence for reopening of the cranial neural tube in mouse embryos treated with cadmium chloride

Summary Use of the whole-embryo culture technique resulted in experiemtal evidence that the pathogenesis of exencephaly in mouse embryos after cadmium chloride treatment results from reopening of the cranial neural tube.     

Preferential excretion of glycated albumin in C57BL-Ks-J mice: Effects of diabetes

Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of editing of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model³.     

Immune-mediated glomerulonephritis induced by mercuric chloride in mice

Summary The BALB/c mouse developed mesangial deposits of immune constituents and light microscopical changes characteristic of immune complex glomerulonephritis after 8 weeks' treatment with mercuric chloride given by s.c. injection. There were no signs of linear of granular immune deposits along the glomerular capillary basement membrane after 2 or 8 weeks. The antigen could not be identified. No antibodies to nuclear or renal structures were found. Using a histochemical method (silver amplification) mercury was detected by light and electron microscopy in tubular and glomerular structures. Mercury was present in secondary lysosomes of the mesangial cells after eight weeks of mercury poisoning.We are deeply indebted to Dr. Gorm Danscher, Institute of Anatomy, B., University of Aarhus, Denmark, for valuable discussions and technical advice. This work was supported by the Swedish Medical Research Council, project no 6536.     

Alopecia induced in young mice by exposure to excess dietary zinc

Summary Second generation mice were exposed to normal (50 ppm, Group I) or excess (2000 ppm, Group II) zinc in the maternal diet during gestation and lactation, then weaned and continued on the mother's diet until sacrifice at 8 weeks. Tibia zinc reflected dietary intake. Group II had reduced plasma copper, body weight, and hematocrit; the second coat of hair appeared late and was lighter in color than Group I, possibly as an effect of copper and pigmentation development and hair growth.     

Kinetic arguments for the existence of a single form of intestinal ornithine decarboxylase during the postnatal development of normal and sparse-fur mutant mice and after EGF treatment

Summary The K_m for ornithine is remarkably constant during the course of postnatal development in both normal and spf mutant mice even if a large but transient increase in ornithine decarboxylase (ODC) activity is noted. Four hours after EGF injection (4 g/g b.wt) to 17-day-old normal and spf mice, a marked stimulation of ODC activity is observed but K_m remains unaffected. These data argue against the existence of multiple forms of ODC in the intestinal mucosa of mice.Supported by grant MA-8923 from the Medical Research Council of Canada. The author is Chercheur-boursier du Fonds de la Recherche en Santé du Québec.     

Hydroxyproline concentration in soluble and insoluble material from serum treated with trichloroacetic acid in postpartum mice

Summary The hydroxyproline concentration in both the soluble and insoluble material from trichloroacetic acid-treated serum from postpartum mice was determined. The hydroxyproline concentration in the insoluble material increased, but that in the soluble material did not increase during the uterine involuting period.     

Inhibition by SMS 201-995 of normal mammary gland growth in mice

Summary Twice daily s.c. injection of 5 ng or 50 ng of SMS 201-995 between 25 and 55 days of age induced a significant retardation of normal mammary gland growth in C3H/He virgin mice, associated with the reduced plasma GH level. Meanwhile, plasma prolactin level and the pattern of estrous cycle were affected little by SMS treatments. The results indicate an involvement of GH in normal mammary gland growth in mice.     

Uptake and toxic effects of heavy metal ions: interactions among cadmium, copper and zinc in cultured cells

Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements. The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.     

Similarities between metallothionein and low molecular weight testicular cadmium-binding protein

Summary The incorporation of³⁵S-cysteine and³H-glutamic acid was studied in mouse hepatic and renal metallothionein and in testicular cadmium-binding protein of similar molecular weight. Preferential incorporation of³⁵S-cysteine over³H-glutamic acid was observed not only in hepatic and renal metallothionein, but also in testicular cadmium-binding protein. When the antigenic reactivity of these proteins was compared, all three proteins reacted with the metallothionein antibody. These similarities suggest that the low molecular weight testicular cadmium-binding protein is apparently metallothionein.     

Carbamazepine inhibits NMDA-induced depolarizations in cortical wedges prepared from DBA/2 mice

There is some doubt as to the mechanism of action of the widely-used anticonvulsant drug, carbamazepine. In cortical wedges prepared from genetically epilepsy-prone DBA/2 mice, carbamazepine at therapeutic concentrations (1–10 M) markedly reduced the depolarization produced by N-methyl-D-aspartate (NMDA). The NMDA sub-type of glutamate receptor has been implicated in the pathogenesis of epilepsy and the inhibitory action of carbamazepine on this response suggests that the anticonvulsant action of the drug may be due to its blockade of NMDA receptor-mediated events.     

Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

Summary A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.     

Uptake and toxic effects of heavy metal ions: Interactions among cadmium,copper and zinc in cultured cells

Summary Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements.The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.     

Chemical evidence for interactions between vitamins E and C

Summary Experimental proof is provided for interactions between radicals of vitamin E/vitamin C as generated by air-oxidized lipids (liquid fraction of subcutaneous chicken fat). Using ESR spectroscopy, hydrogen atom exchange is shown to take place between vitamin C and the radical of vitamin E. Sequential consumption of these two vitamins in oxidized lipid, first vitamin C then vitamin E, is demonstrated by means of differential pulse polarography. These results elucidate the in vitro radical scavenging functions attributed to vitamin E and vitamin C as well as their synergism in lipid antioxidation.The authors very much thank Dr A. Dieffenbacher and P. Ducret for the preparation of the chicken fat fraction.