Termination of pregnancy in mice following antiserum administration to modified chicken riboflavin carrier protein.

Rabbit antibodies to native riboflavin carrier protein (RCP), are to a large extent directed towards conformational epitopes and antibodies to disulphide bond reduced carboxymethylated RCP (RCM-RCP) are towards sequential epitopes. The major cyanogen bromide (CNBr) fragments and tryptic fragments of RCM-RCP interact with both antiserum to RCM-RCP and RCP. Passive immunization of pregnant mice with antibodies to RCM-RCP results in bioneutralization, leading to termination of pregnancy. Recently, a major tryptic fragment of RCM-RCP (24 +/- 2 kd) which could assume conformation at the antibody combining site of native RCP, obtained following mild trypsinization has been identified [Natraj et al. J. Biosci, 15 (1990) 341]. Rabbit antibodies to RCM-RCP treated with trypsin generated antibodies of low titer which interacted with RCM-RCP as well as RCP. The interaction of this antibody with RCP was of high affinity and could be displaced with RCP. The bioneutralizing ability of the antibody was demonstrated by its ability to cause termination of pregnancy in mice.     

Absorption of cadmium after a long-term oral administration of cadmium to dogs

A long-term experiment using beagle dogs to investigate the absorption of cadmium was conducted. The dogs in the experimental groups were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day. The cadmium concentration in the blood increased continuously, gradually reaching a steady state following the administration of cadmium. The cadmium excreted daily in urine increased continuously. The cumulative excreted amount of cadmium in urine was calculated by using the trapezoidal rule based on the data of excretion of cadmium in urine. Then the absorbed fraction of administered cadmium was estimated on the basis of the relationship between the cumulative excreted amount of cadmium in urine and the cumulative administered dose of cadmium after the cadmium concentration in blood reached a steady state. The absorbed fraction of cadmium decreased with an increase in the administered dose of cadmium. A dose-dependent increase between the absorbed amount and the administered dose was observed.     

Modulation of rat serosal mast cell biochemistry by in vivo dexamethasone administration

To examine steroid-induced biochemical alterations in the mast cell secretory process, rats were injected with intramuscular dexamethasone or saline for 4 days, and serosal mast cells and lung tissue were obtained from each group. Radioligand binding studies utilizing 1-[propyl-1,2-3H]dihydroalprenolol (3H-DHA) demonstrated a 23.1 +/- 0.8% increase in rat lung beta-adrenergic receptors in steroid-treated rats, but the mast cell beta-adrenergic receptors were unaffected. Neither resting mast cell cyclic adenosine 3':5'-monophosphate (cAMP) levels nor the degree of cAMP augmentation induced by isoproterenol were changed by steroid administration. Mast cells from rats treated with dexamethasone released only 48.6 +/- 8.9 and 58.8 +/- 6.0% of the beta-hexosaminidase released from saline-treated rat mast cells when sensitized with anti-dinitrophenyl (DNP) IgE and challenged with DNP-bovine serum albumin antigen or the calcium ionophore A23187, respectively. [3H]serotonin release in cells from steroid-treated rats was 41.8 +/- 7.9 and 87.6 +/- 2.6% of control release stimulated by antigen or A23187, respectively. [14C]arachidonic acid incorporation into mast cell phospholipids followed by antigen or A23187 challenge revealed that cells from dexamethasone-treated rats release 61.3 +/- 15.6% and 62.1 +/- 11.8% of labeled metabolites, respectively, compared to controls. The addition of exogenous arachidonic acid 5 min prior to antigen challenge caused a similar decrease in mediator release in cells from saline- and steroid-treated rats (36.7 +/- 6.1 and 38.4 +/- 0.9%, respectively). When arachidonic acid was added to sensitized cells after specific antigen, no significant changes in beta-hexosaminidase release were noted in either group. Chronic in vivo dexamethasone administration markedly decreases mast cell mediator release without changing resting cAMP levels. The release of arachidonic acid metabolites is reduced in steroid-treated cells, possibly through the inhibition of phospholipases. Exogenous arachidonic acid cannot overcome this inhibition, suggesting that an earlier step in phospholipid metabolism, perhaps involving phospholipase C, may be important.     

Stimulation of gastric glucagon secretion by epinephrine administration in dogs

To determine the response of gastric A-cells to adrenergic substances, immunoreactive glucagon was determined simultaneously in the jugular vein and in the left gastroepiploic vein of totally depancreatized dogs. Under basal conditions a significant gradient of glucagon concentrations between the jugular and gastric veins was observed, whereas plasma insulin values were almost undetectable. Intravenous administration of epinephrine elicits a prompt and significant increase in glucagon concentrations in the gastric vein which persist during the time of hormone infusion. To ensure adequate adrenergic blockade, blockers were infused before epinephrine administration. Accordingly, after phentolamine, the infusion of epinephrine failed to increase gastric glucagon concentrations, while after propranolol, epinephrine induced a significant release of gastric glucagon. These results indicate that epinephrine stimulates gastric glucagon secretion and that this effect is mediated through alpha-adrenergic receptors.     

Biological half-time and body burden of cadmium in dogs after a long-term oral administration of cadmium

To investigate the kinetic behavior of cadmium, we conducted a long-term oral administration experiment, using beagle dogs. The experimental animals were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day in the form of cadmium chloride for 8 yr. A single injection of cadmium (as CdCl2) into dogs was also performed in order to obtain fundamental kinetic information for a dog. The kinetic behavior of cadmium in chronic experiment is described theoretically, using a two-compartment model. The model was selected based on the elimination pattern of cadmium from the blood in the single injection experiment. The parameters of the model were estimated from the acute and chronic experimental data. The theoretical value of the cumulative amount of cadmium excreted in urine agreed with the experimental one. This result suggests that the two-compartment model used in this study is useful to elucidate the kinetic behavior of cadmium after a long-term exposure to cadmium. The terminal biological half-time in the two-compartment model was estimated at about 1 to 2 yr for both male and female dogs given 1, 3, 10, and 50 mg of cadmium, and for the male dog given 100 mg of cadmium, but only 0.3 to 0.5 yr for the female dog given 100 mg of cadmium. The amount of cadmium in the central compartment and tissue compartment increased continuously and then gradually reached a steady state. The amount of tissue compartment was much higher than that of the central compartment for each beagle dog.     

Inhibition of progesterone synthesis in placenta by administration of dexamethasone to pregnant rats

Glucocorticoid receptors have been detected in placenta from several species, including the rat, although the biological function of corticoids is unknown in placenta from the latter species. The present experiments examined the effect of glucocorticoid treatment on placental progesterone biosynthesis from endogenous precursors by incubated basal zone trophoblast and labyrinthine zone of placentas from adrenalectomized-ovariectomized rats at the end of pregnancy. It was found that a higher proportion of synthesized progesterone was retained in the tissue than that released into the incubation medium. Treatment of rats on the 17th-18th day of pregnancy with 10 micrograms/ml of dexamethasone in the drinking saline for 3 days, produced a significant inhibition of progesterone detected in tissue and medium of incubated placental zones. In vitro addition of dexamethasone (10(-4) M) was also effective in reducing progesterone in the placental zone studied (LZ). Serum progesterone of intact rats was in the range of rats near parturition (approx 25 ng/ml) and dropped to almost undetectable levels in rats with adrenalectomy and ovariectomy, with or without dexamethasone treatment, suggesting that in late pregnancy the rat placenta does not contribute significantly to circulating levels of progesterone. This glucocorticoid effect could not be extended to estrogens, as we, in accord with the work of other groups, failed to detect estrogen synthesis in rat placenta. It is suggested that a function for glucocorticoid receptors in rat placenta may be the inhibition of local progesterone production.     

Paradoxical hyperglucagonemia after oral administration of glucose in diabetic dogs. Impact of the cholinergic nervous system

Alloxan diabetic dogs with insulin deficiency showed a transient but significant rise in glucagon levels after oral glucose load (1 g/kg). Pretreatment with atropine sulfate (0.2 mg/kg intravenously) totally suppressed this increase. So, the transient paradoxical rise of glucagon level observed in diabetic dogs after glucose intake is under cholinergic control.