cortisol-succinate--sodium-salt and hydrocortisone-acetate

Both acute and chronic stress can impair maternal behavior and increase rates of infant abuse in several species. The mechanisms inducing these effects are unknown, but experimental manipulation of circulating corticosterone levels alters maternal behavior in rats, and circulating or excreted cortisol concentrations have been found to correlate either positively or negatively with maternal behavior in humans and nonhuman primates. In this study, therefore, we experimentally tested the hypothesis that both acute and chronic treatment with exogenous glucocorticoids would alter maternal behavior in a primate, the common marmoset (Callithrix jacchus). Multiparous females, approximately 3-5 weeks postpartum, received daily injections of either cortisol (hydrocortisone sodium succinate and hydrocortisone acetate; N=7) or vehicle (N=7) for 8 days, and maternal behavior was characterized under baseline conditions as well as during exposure to a noise stressor. Cortisol treatment successfully elevated both morning and afternoon plasma cortisol concentrations and suppressed circulating levels of adrenocorticotropic hormone. In home-cage observations, cortisol-treated females carried their infants significantly less than control mothers, and in noise-stressor tests, several hours after the first cortisol or vehicle treatment, cortisol-treated mothers inspected their infants significantly more often than controls. Aggression towards infants was infrequent and mild, and did not differ between treatment groups. These findings provide the first experimental evidence that cortisol elevations can alter maternal behavior in primates. As these effects were limited in scope, however, they suggest that other stress-responsive hormones or neuropeptides may additionally play a role in mediating the effects of stress on maternal behavior.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Callithrix; Female; Hydrocortisone; Maternal Behavior; Noise; Postpartum Period; Progesterone; Stress, Psychological

A reverse-phase high-performance liquid chromatographic (HPLC) method to determine hydrocortisone acetate, hydrocortisone hemisuccinate and lidocaine is described in this paper. The separation was made in a LichrCART C(18) column using a methanol-NaH(2)PO(4)/Na(2)HPO(4) (0.1 mol L(-1)) (pH=4.5) buffer solution as a mobile phase in isocratic mode (60:40 (v/v)). The mobile phase flow rate and the sample volume injected were 1 mL min(-1) and 20 micro L, respectively. The detection was made with a diode-array detector measuring at the maximum for each compound. Quantification limits ranging from 0.18 to 0.84 micro g L(-1) were obtained when the peak area was measured. The method was applied in pharmaceutical formulations that were compared with those obtained by through multivariate regression spectrophotometry and micellar capillary electrophoresis (MEKC). HPLC results are in accordance with the results obtained by MEKC. The spectrophotometric method was suitable only for synthetic samples.

Topics: Anesthetics, Local; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Hydrocortisone; Lidocaine; Multivariate Analysis; Regression Analysis; Spectrophotometry

We observed a remarkable augmentation in the rate of hydrolytic breakdown of HCHS following exposure to corticosteroid therapy. This underscores the need for a careful reappraisal of its dosage in long term therapy. In such an event the uncharged ester may be the preferred drug of choice.

Topics: Animals; Carboxylic Ester Hydrolases; Drug Interactions; Enzyme Activation; Hydrocortisone; Male; Microsomes, Liver; Rats

Topics: Aldosterone; Animals; Cataract; Chick Embryo; Disease Models, Animal; Hydrocortisone

The present study has provided evidence for the existence of three distinct carboxylesterases involved in the hydrolysis of steroid esters, where two enzymes are possibly responsible for the metabolism of hydrocortisone hemisuccinate (HCHS) at pH 5.5 and 8.0, and a third enzyme for the metabolism of hydrocortisone acetate (HCAC) at pH 8.0, in isolated rat liver microsomes. The activity of all three enzymes in rat liver was induced significantly by the administration of phenobarbital while no such function in enzyme activity was observed in animals receiving 3-methylcholanthrene or benzo[a] pyrene under similar experimental conditions. The increase in the activity of HCHS esterase I (HCHS-E1) active at pH 5.5, HCHS esterase II (HCHS-E2) active at pH 8.0, and HCAC esterase (HCAC-E) was approximately 7 to 8, 3- and 3-fold respectively. On the other hand, the degree of induction of nonspecific microsomal carboxylesterase acting on p-nitrophenylacetate (PNPA) was significantly less. The Km values for the hydrolysis of HCHS at pH 5.5 and 8.0 and HCAC by rat liver microsomes obtained from control rats were 2.45, 2.02 and 1.6 mM, respectively, and these Km values were not changed significantly in preparations obtained from rats treated with phenobarbital. The distinct in vitro responses displayed by hepatic microsomal steroid esterases to various inhibitors were able to distinguish three different enzymes which also differed from nonspecific carboxylesterases. The activity of HCAC-E was inhibited by NaAsO2 and AgNO3 while that of HCHS-E1 and HCHS-E2 remained unaffected. Selective inhibition of HCHS-E1 by NaF, HgCl2 and p-chloromercuribenzoate and that of HCHS-E2 by NiSO4 indicated the possible existence of different enzymes or isozymes of a carboxylesterase catalyzing HCHS hydrolysis. The effects elicited by the inhibitors on the activity of PNPA esterase were different from those observed with steroid esterases. Furthermore, the present study has also indicated species variations in the distribution of steroid esterases in the livers of rat, mouse, dog and cat.

Topics: Animals; Carboxylic Ester Hydrolases; Female; Hydrocortisone; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Microsomes, Liver; Nitrophenols; Rats; Species Specificity

Hydrocortisone acetate or hemisuccinate (75 mg/kg body mass) applied to rats i.m. and/or s.c. on the 9th and 10th postnatal days causes a precocious decrease of sialic acid content of the small intestinal brush-border membrane. On the 15th postnatal day the bound sialic acid of the whole membrane fraction drops to almost half of the values of control animals and to one third of the control values for the papain-solubilized membrane proteins. The hydrocortisone effect is manifested on isoelectric focusing zymograms by a faster increase of pI of the solubilized brush-border enzymes on the 12th and 15th postnatal days.

Topics: alpha-Glucosidases; Animal Population Groups; Animals; Animals, Suckling; Glucosidases; Hydrocortisone; Isoelectric Point; Jejunum; Membrane Proteins; Microvilli; N-Acetylneuraminic Acid; Neuraminidase; Rats; Sialic Acids

The effect of corticosteroid on autologous minced cartilage transplanted into facsimile synovial cavities has been studied. The soluble form of hydrocortisone, as the sodium succinate, reduced proteoglycan loss from cartilage in a dose-dependent manner. In contrast, insoluble hydrocortisone acetate, if given directly into the cartilage-containing cavity, enhanced proteoglycan loss. Injection of the same dose of drug into the inflamed lining tissue reversed this effect. These findings suggest that intra-articular steroid injection may enhance cartilage damage if insoluble preparations are used, but that this may be overcome by injecting into the inflamed lining tissue rather than into the cavity itself.

Topics: Air; Animals; Cartilage; Hydrocortisone; Male; Mice; Proteoglycans

Topics: Animals; Cyclophosphamide; Cytotoxicity, Immunologic; Hydrocortisone; Mice; Mice, Inbred Strains; Radiation Chimera; T-Lymphocytes; Thymus Gland; Vaccinia virus

The selective homing of labelled cells from lymph nodes and peritoneal exudate to lymph nodes and spleens is strongly inhibited after an in vivo administration of steroid hormones, cyproterone acetate, hydrocortisone acetate and hydrocortisone succinate. At the same time the number of lymphocytes and monocytes is greatly reduced in the peripheral blood. This decrease and changes in recirculation of lymphocytes and monocytes are due not to the lysis of cells but to an altered distribution of them in the body and an increased trapping in the bone marrow. The values in the peripheral blood picture are very rapidly reconstituted after the level of the soluble, short-term acting steroid--hydrocortisone succinate--in the body had decreased, and the transferred labelled cells re-enter the lymph nodes while their number in bone marrow is reduced. The altered distribution of cells in the body that is obviously not advantageous for the immune reactions may be one of the causes of the immunosuppressive effect of the steroids.

Topics: Animals; Bone Marrow Cells; Cell Survival; Cyproterone; Female; Hydrocortisone; Lymph Nodes; Lymphocytes; Male; Mice; Mice, Inbred Strains; Organ Size; Spleen; Thymus Gland