Alopecia induced in young mice by exposure to excess dietary zinc

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.     

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.     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

Summary 24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Block to pseudopregnancy in mice caused by exposure to male urine

Zusammenfassung Mäuseweibchen, die durch Paarung mit vasektomierten Männchen scheinträchtig gemacht worden waren, wurden dem Urin von Männchen eines anderen Stammes ausgesetzt. Dadurch wurde die Pseudogravidität unterbrochen. Diese Beobachtung gleicht der Unterbrechung der Trächtigkeit frisch begatteter Weibchen durch den Urin fremdstämmiger Männchen und bestätigt auch die Beschleunigung des Eintritts des Östrus durch die Gegenwart der Männchen.     

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.Received 23 February 2005; received after revision 3 May 2005; accepted 13 May 2005     

Forskolin supresses seizures induced by pentylenetrazol in mice

Summary Forskolin, an adenylate cyclase activator when injected s.c. (1 mg/kg) in mice, caused an elevation of cAMP in the forebrain and cerebellum of up to 170% and 130%, respectively. The treatment was found to prevent seizures induced by pentylenetetrazol. This suppression had subsided 30 min after the injection, when cAMP level was again normal in the cerebellum but still elevated in the forebrain.     

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.     

Proopiomelanocortin expression in the skin during induced hair growth in mice

We demonstrate for the first time a hair cycle-dependent gene and protein expression of proopiomelanocortin in mouse skin in vivo. Northern blot detected POMC mRNA with an apparent size of 0.9 kb in anagen but not telogen skin. Western blot emphasized a specific protein of 30–33 kDa recognized by anti -endorphin in late but not early anagen or telogen skin. By immunocytochemistry, -endorphin antigen was localized in the sebaceous gland in a hair cycle dependent manner.     

Duration of hornet sleep induced by ether anesthesia is curtailed by exposure to sun or UV irradiation

Irradiation of hornets anesthetized by diethyl ether curtails their sleep duration from the ordinary 20–30 min to a mere 2–3 min. This effect on sleep is dependent on the intensity of the sun irradiation or, when exposed to monochromatic UV at 366 nm, on the duration of the irradiation. Of the various hornet cuticular areas of the body, the yellow cuticular areas of the abdominal segments are the most sensitive to the treatment. We assume that the cuticles of both live and dead hornets act as a converter of light to electric energy.     

Circling behavior induced by phencyclidine in mice and its inhibition by naloxone

Summary Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.Acknowledgment. We are grateful to Professor A. Kalir for the donation of PCP. Correspondence and reprint requests should be addressed to A. M. Korczyn.     

Changes of hormonal status in young mice by restricted caloric diet. Relation to lifespan extension. Preliminary results

Summary The maintainance of mice on a reduced caloric diet for 6 weeks starting from weaning time produces persistent changes in their hormonal status as reflected by differences in blood levels of gonadal and adrenal steroids. The changes might express a permanently different hypothalamic regulation. This might accoutn for a prolongation of their life span.This work has been supported by the Swiss National Fund for Scientific Research, grant No. 3.8750.72. I thank Miss M. Hämmerli of Ciba-Geigy AG, Basel, for her participation in the low caloric diet experiments.     

The enhanced induction of metallothionein by zinc,its half-life in the marine fishPleuronectes platessa,and the influence of stress factors on metallothionein levels

Summary Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 g/g to 300 g/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of³⁵S cysteine at 11°C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.     

Erythropoietin formation during hypoxia in mice with impaired responsiveness to erythropoietin induced by irradiation or 5-fluorouracil injection

Summary Plasma erythropoietin levels during continuous exposure to hypobaric hypoxia in mice with marrow aplasia induced by whole body X-irradiation or 5-fluorouracil injection were higher than in control mice similarly exposed. These findings give support to the hypothesis that a relationship exists between erythropoietin production rate and erythroid responsiveness to the hormone.Supported by Conicet and Subcyt grants. Request for reprints should be addressed to C. E. B.     

Hyperthermia-induced apoptosis and the inhibition of DNA laddering by zinc supplementation and withdrawal of calcium and magnesium in suspension culture of tobacco cells

In the present paper we report examination of stereotypic hallmarks of apoptosis in heat-treated tobacco cells. Hyperthermia (44 °C, 4 h) caused apoptosis in 53.6% of cells when assayed 24 h after heat treatment. The induction of apoptosis by heat treatment was confirmed by flow cytometric assay. Cytological observations revealed condensation of the cytoplasm and nucleus, as well as nuclear collapse. DNA ladders were observed in DNA extracted from heat-treated cells, whereas DNA from control cells remained undegraded. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay revealed that 51.8% of the heat-treated cells (44 °C, 4 h) show positive reaction after a 24-h recovery. When cells were cultured in a medium supplemented with 0.4–5.0 mM ZnSO₄, internucleosomal DNA fragmentation induced by heat shock was completely negated. Strikingly, when cells were cultured in Ca²⁺ and/or Mg²⁺ free medium for 44 h followed by heat treatment, DNA laddering was not observed. The results suggest hyperthermia-induced apoptosis and a correlation between the regula tion of endonucleases and heat shock signal in apoptotic tobacco cells. Received 17 September 1998; received after revision 4 January 1999; accepted 4 January 1999     

Splenic B-cell activation in lipopolysaccharide-non-responsive C3H/HeJ mice by lipopolysaccharide ofPorphyromonas gingivalis

Porphyromonas gingivalis 381 lipopolysaccharide (LPS) definitely exhibited mitogenic activity in purified B-cells, separated from spleens of LPS-responsive C3H/HeN mice and LPS-non-responsive C3H/HeJ mice by using a magnetic cell sorting system. The mitogenic activity induced byP. gingivalis LPS was incompletely inhibited by polymyxin B.P. gingivalis LPS also induced a higher production of interleukin-6 (IL-6) in splenic B-cells of C3H/HeN mice as compared withEscherichia coli LPS. Furthermore,P. gingivalis LPS, but notE. coli LPS, induced definite IL-6 production in C3H/HeJ mice.P. gingivalis LPS increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B-cells of both C3H/HeN and C3H/HeJ mice. Additionally, radioiodinatedP. gingivalis LPS, similarly toE. coli LPS, bound to a 73-kDa protein on C3H/HeJ as well as C3H/HeN B-cells. ThusP. gingivalis LPS may activate B-cells of C3H/HeJ as well as C3H/HeN mice via the LPS-specific binding protein on the cells.     

Reversal of net secretion to net absorption of potassium in rat large intestine by dietary potassium depletion

Summary Feeding rats a diet low in potassium and high in sodium for 2 weeks led to a reversal of net potassium secretion to net potassium absorption in ligated segments of distal large intestine (colon descendens and rectum) under in-vivo conditions. This change in the direction of net potassium transport is probably important for the maintenance of potassium homeostasis.The technical assistance of Mrs U. Seeliger is gratefully acknowledged.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.