Effects Of Glucocorticoid Treatment Research Articles

Retrospective analysis of 18 cases of antithyroid drug (ATD)-induced agranulocytosis.

In this study, we retrospectively analyzed 18 patients in whom antithyroid drug (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All patients were more than 20 years of age, and we saw no correlation between age and the development of agranulocytosis. In 17 of 18 patients, ATD-induced agranulocytosis developed within 2 to 12 weeks of starting ATD treatment. Development of agranulocytosis was related to the dose of ATD. In some patients, agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte counts failed to predict all case occurrences. Fever and sore throat were the earliest symptoms of agranulocytosis; patients who developed either of these symptoms were closely monitored immediately with WBC and granulocyte count examinations. In this series of patients, treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the effectiveness of glucocorticoid treatment was not confirmed.

Satisfactory remission in a case of IgD myeloma: Effectiveness of glucocorticoid treatment

IgD myeloma is an infrequent type of multiple myeloma and is characterized by an aggressive clinical behavior and a short survival time. No satisfactory treatments have thus far been established. Recently we treated a patient with IgD(λ)-type myeloma with glucocorticoids, and succeeded in achieving a complete remission. This case seems to indicate a usefulness of glucocorticoid monotherapy for treating IgD myeloma. Am. J. Hematol. 66:62–63, 2001. © 2001 Wiley-Liss, Inc.

Vertebral blood flow and bone mineral density during long-term corticosteroid treatment: An experimental study in immature pigs.

Bone mineral density and regional blood flow were measured in pigs during long-term methylprednisolone treatment. To investigate possible changes in bone mineral density and vertebral blood flow during long-term glucocorticoid treatment. Steroid-induced vertebral osteonecrosis preferentially involves endplates and adjacent cancellous bone. The precise etiology of vertebral osteonecrosis during long-term glucocorticoid treatment is unknown. Twenty-four 10-week-old female Danish landrace sister pigs from 12 litters were treated in two groups. Twelve animals received oral methylprednisolone for 3 months at a daily dose of 100 mg. The 12 sister pigs received no steroid treatment and served as controls. Regional blood blow was measured by means of microspheres in predefined regions of the C6, T11, and L6 vertebrae. In vitro DEXA scanning of the L2-L4 vertebra was performed to assess bone mineral density. Vertebral cancellous bone and endplate regional blood flow were decreased in the C6 and L6 vertebrae among corticosteroid-treated pigs compared with that of controls.- Width-adjusted lumbar vertebral bone mineral density (g/cm3) was unchanged, whereas projectional lumbar vertebral bone mineral density (g/cm2) was decreased in corticosteroid-treated pigs. Long-term methylprednisolone treatment decreases vertebral bone blood flow mainly in cancellous bone and endplates. This may be an important factor in the pathogenesis of osteonecrosis secondary to glucocorticoid treatment. Lumbar vertebral bone mineral density was unchanged in growing pigs on long-term glucocorticoid treatment when expressed as volumetric bone density. The effect of glucocorticoid treatment on vertebral bone mineral density appears to depend on whether it is expressed as projectional (g/cm2) or volumetric bone mineral density (g/cm3). Vertebral and longbone growth was reduced during methylprednisolone treatment.

Regulation of type-2 corticotropin-releasing hormone receptor mRNA in rat heart by glucocorticoids and urocortin.

A novel subtype of corticotropin-releasing hormone (CRH) receptor, designated type-2 CRH receptor (CRHR-2), has been cloned by a number of laboratories, and its mRNA has been found to be distributed not only in the brain but in peripheral tissues such as heart and skeletal muscle. To date, however, the regulation of CRHR-2 mRNA is poorly understood. Therefore, we examined the effect of glucocorticoid treatment, adrenalectomy, and systemic administration of urocortin, a possible endogenous ligand for CRHR-2, on heart CRHR-2 mRNA levels in male Wistar rats, using in situ hybridization histochemistry. CRHR-2 mRNA in the heart was significantly decreased 9 h after systemic administration of urocortin (5 microg/kg b.w.). Systemic administration of corticosterone (CORT; 10 mg/rat/day for 12 days) or CORT pellet (200 mg) implant for 7 and 14 days also decreased CRHR-2 mRNA in the heart, whereas it was unchanged 7 days after adrenalectomy. Thus, similar regulation of CRHR-2 mRNA in the rat heart by its ligand and glucocorticoids was observed. The precise mechanism of the regulation of CRHR-2 mRNA in the heart and the physiologic significance of cardiac CRHR-2 remains to be elucidated.

Satisfactory remission in a case of IgD myeloma: Effectiveness of glucocorticoid treatment

IgD myeloma is an infrequent type of multiple myeloma and is characterized by an aggressive clinical behavior and a short survival time. No satisfactory treatments have thus far been established. Recently we treated a patient with IgD(lambda)-type myeloma with glucocorticoids, and succeeded in achieving a complete remission. This case seems to indicate a usefulness of glucocorticoid monotherapy for treating IgD myeloma.

Hypocortisolism in chronic pelvic pain: Effect of glucocorticoid treatment on pain symptomatology

Hypocortisolism in chronic pelvic pain: Effect of glucocorticoid treatment on pain symptomatology

Effects of glucocorticoid treatment on regenerating skeletal muscles in the rat

Summary Introduction. Regeneration of the soleus and extensor digitorum longus muscles of Wistar male rats was induced by an injection of snake venom (2 μ g, Notechis scutatus scutatus). Methods and results. Rats were treated for 14 to 16 days with dexamethasone (sub-cutaneous, 1 mg/kg on a daily basis) or not (control). Twenty five days after venom injection, the mass of the venom-treated extensor digitorum longus in dexamethasone rats was decreased when compared to control rats ( P P Conclusion. The results of this preliminary study suggest that dexamethasone treatment inhibits both the growth of extensor digitorum longus and the maturation of the soleus during regeneration.

Effect of Glucocorticoid Treatment on Biochemical and Hormonal Blood Parameters in Early Pregnant Gilts

Twenty Polish Landrace gilts were grouped immediately after mating as follows: Experiment I-- Group 1 (5 gilts), control animals and Group 2 (5 gilts), injected i.m. with dexamethasone (30 mg/kg) at 12-h intervals from day 13 to day 22 of pregnancy; Experiment II--Group 3 (5 gilts), injected i.m. with corn oil from day 13 to day 22 of pregnancy and Group 4 (5 gilts), injected i.m. with hydrocortisone acetate (250 mg) at 12-h intervals from day 11 to day 20 of pregnancy. Gilts were placed in metabolic cages on day 7. On days 34-36 of pregnancy gilts were slaughtered and blood samples were collected. Serum was used for analysis of aspartate aminotransferase (S-ASAT), alanine aminotransferase (S-ALAT), alkaline phosphatase (S-ALP), S-cholesterol, S-triglycerides, S-fructosamine, S-urea, S-total protein, and for electrophoretic fractionation of serum proteins, corticosteroid-binding globulin (CBG), cortisol, progesterone, thyroxine (T4) and free T4. There were no significant differences between groups in embryonic survival or in number of viable fetuses after treatment with glucocorticoids. The activity of S-ALP was lower (p < 0.05) in Group 4 than in Group 3 (0.5 vs 1.2 mukat/l). Group 4 had higher (p < 0.05) levels of S-triglycerides (1.17 vs 0.73 mmol/l), S-cholesterol (5.4 vs 2.7 mmol/l), S-total protein (110.5 vs 93.3 g/l), S-albumin (56.3 vs 43.3 g/l) and alpha 2-globulin concentrations (18.0 vs 14.3 g/l) than Group 3. The hydrocortisone-treated gilts had lower (p < 0.05) CBG (6.8 vs 21.3 nmol/l) and beta 1-globulin (3.25 vs 5.0 g/l) concentrations than the oil-treated ones. Concentrations of T4 were lower (p < 0.05) in Groups 2 (61.3 nmo/l) and 4 (49.0 nmol/l) compared with control Groups 1 and 3 (88.2 and 97.0 nmol/l, respectively). Overall, the treatment of early pregnant gilts with hydrocortisone acetate resulted in decreased levels of S-ALP, CBG, beta 1-globulin and T4, and in increased levels of S-cholesterol, S-triglycerides, S-total protein, S-albumin and alpha 2-globulin. The only effect of dexamethasone was a lowering of T4. There were no differences in free T4, S-fructosamine or S-urea between controls and treatments. Furthermore a negative correlation between triglycerides concentrations and the number of embryos (r = -0.76, p < 0.05) was found in control untreated and oil-treated pregnant gilts.

GLUTAMINE SYNTHETASE EXPRESSION AND IMMUNOLOCALIZATION IN THE DEVELOPING RAT LUNG. † 1831

Although the lung is known to be a major producer of glutamine and contributes to glutamine homeostasis, little is known about glutamine during development. We hypothesize that glutamine synthetase (GS) undergoes changes in activity and steady state mRNA from infancy to adulthood. GS activity and RNA were measured in the lungs of rat term fetuses, 5, 10, and 19-day-old infants, and adults following treatment with saline (SAL) or 0.2 mg/kg dexamethasone (DEX). Significant interactions between treatment and age effects were noted for both mRNA and specific activity indicating that the degree of difference between SAL and DEX treatment groups depended on age (2 way ANOVA). Pairwise comparisons indicate that mRNA quantity and specific activity were greater in the 5-day DEX group. Within the SAL treatment set, mRNA levels did not differ among age groups; however, specific activity of the 19-day group was greater than fetal, 5-day and 10-day specific activities. Within the DEX treatment set, the mean mRNA level of the 5-day group was greater than in the other age groups; however, DEX treatment did not alter the specific activities among age groups. Immunohistochemical analysis demonstrates that GS enzyme is located primarily in the smooth muscle layer of the pulmonary vasculature. These data demonstrate that: 1) GS responds to exogenous glucocorticoids prior to the endogenous glucocorticoid surge; and 2) the effects of glucocorticoid treatment are blunted when endogenous glucocorticoids are elevated. Our data suggest that: 1) glucocorticoid receptors are unavailable to exogenous glucocorticoids when endogenous glucocorticoids are elevated; and 2) localization of GS in the pulmonary smooth muscle layer permits rapid release of glutamine into the circulation during periods of high glutamine demand. Supported by NIH Grant#RO1-HD29279.

Glucocorticoids are ineffective in alcoholic hepatitis: a meta-analysis adjusting for confounding variables.

The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment may be different (beneficial or harmful) in special patient subgroups. These results do not support the routine use of glucocorticoids in patients with alcoholic hepatitis, including those with encephalopathy. Whether other subgroups may benefit needs further investigation using the individual patient data from the published trials and testing in new randomised trials.

Corticosteroid regulation of IL-1 receptors in the mouse hippocampus: effects of glucocorticoid treatment, stress, and adrenalectomy.

Interleukin-1 (IL-1) and glucocorticoid hormones represent two key mediators involved in the modulation of the neuroimmunoendocrine response to stress. IL-1 is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. In the immune system, glucocorticoids modulate IL-1 production and a number of IL-1 receptors. However, little information is currently available about the modulatory effects that glucocorticoids might exert on IL-1 receptors in the central nervous system. To this purpose, we carried out a series of studies to investigate the effects of various manipulations of the HPA axis on IL-1 binding to the murine hippocampus. Our results show that IL-1 receptor levels in the hippocampus were slightly decreased below control values in dexamethasone (DEX)-treated animals (0.25 or 1 mg/kg i.p. every 12 h) either in subchronic (5 doses) or chronic (8 days) treatments. Corticosterone (CORT) resulted in a small reduction in IL-1 receptors only when injected subchronically at the dose of 5 mg/kg. When it was given at a lower dose (1.25 mg/kg), injected chronically or implanted subcutaneously as CORT pellets for 8 days, no effect was observed. Neither glucocorticoid modified IL-1 binding when administered as a single injection. Saturation studies after subchronic corticosteroid treatment did not reveal modifications in the number and/or affinity of IL-1 receptors in the hippocampus. The regulation of IL-1 receptors by glucocorticoids was also studied following stimulation of IL-1 production by lipopolysaccharide (LPS).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone density and turnover in Addison's disease: effect of glucocorticoid treatment

Osteoporosis is a well-known side-effect of chronic treatment with glucocorticoids. We have studied vertebral bone mineral density (BMD) and biochemical markers of bone metabolism in 30 patients diagnosed of Addison's disease (AD) to determine the effect of long-term replacement treatment with hydrocortisone (30 mg/day) or prednisone (7.5 mg/day). Lumbar bone mineral density was measured with dual energy X-ray absorptiometry in L-1–4 in two occasions, separated by 12 months. BMD in premenopausal women and men with AD was similar to healthy controls and postmenopausal women had slightly lower results. Rate of change of bone density followed up over a period of 12 months was −0.82%. Bone loss was not influenced by duration or type of steroid treatment. Biochemical parameters, serum calcium, alkaline phosphatase, osteocalcin, procollagen type I, PTH and 25(OH)vitamin D were within normal limits. Our results show that in patients with AD, after replacement with low doses of glucocorticoids there is no significative trabecular bone loss neither modifications in bone formation markers.

Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells.

There is growing evidence for the involvement of Ca2+ in the programmed cell death (apoptosis) of lymphocytes, but the nature of glucocorticoid-induced Ca2+ fluxes and their role in the cell death pathway are poorly understood. In the study reported here, we assessed the effect of glucocorticoid treatment on intracellular Ca2+ homeostasis in W7MG1 mouse lymphoma cells. Levels of cytosolic Ca2+ were measured using the intracellular Ca2+ indicator fura2 AM, and total cellular Ca2+ was measured by atomic absorbance spectroscopy. The level of Ca2+ within internal stores, including the endoplasmic reticulum (ER), was estimated by measuring the increase in cytosolic Ca2+ induced by either ionomycin, an ionophore that mobilizes Ca2+ from a variety of internal stores, and by thapsigargin, a specific inhibitor of the ER-associated Ca(2+)-ATPase that mobilizes Ca2+ from the ER. Glucocorticoid treatment induced a significant decrease in ionomycin- and thapsigargin-mobilizable Ca2+ stores that was accompanied by an initial decrease in total cellular Ca2+, followed by a modest increase in both total cellular Ca2+ and cytosolic Ca2+. The glucocorticoid-induced depletion of internal Ca2+ stores was receptor mediated and occurred after a delay corresponding to the time required for glucocorticoid receptor complexes to regulate gene transcription. Mobilization of ER-associated Ca2+ stores by thapsigargin treatment induced DNA fragmentation and cell death similar to that observed after glucocorticoid treatment. These findings suggest that a mobilization of Ca2+ from internal stores may be a critical step in the apoptotic pathway of mouse lymphoma cells.

Glucocorticoid regulation of preproenkephalin gene expression in the rat forebrain

The effects of glucocorticoids on the levels of preproenkephalin (PPE) mRNA in the rat forebrain were analyzed with in situ hybridization and dot blots. In adrenally-intact rats, high levels of PPE mRNA, as assessed by in situ hybridization, were localized in the caudate-putamen, nucleus accumbens, central amygdala, and ventrolateral ventromedial hypothalamus (VMHVL), and low levels in the hippocampus. After adrenalectomy, the density of PPE mRNA-positive cells and the level of PPE mRNA/cell were decreased in all regions except the hippocampus. Acute treatment with corticosterone (CORT) in adrenalectomized rats increased the level of PPE mRNA/cell in the caudate-putamen and VMHVL. In intact rats, chronic treatment with CORT increased the density of PPE mRNA-positive cells in the caudate-putamen and hippocampus, and the level of PPE mRNA/cell in the caudate-putamen and nucleus accumbens. The effect of chronic CORT treatment on PPE mRNA in the striatum, amygdala, hippocampus and mediobasal hypothalamus was assessed with dot blots. Chronic CORT treatment increased PPE mRNA levels in the caudate-putamen and hippocampus. There was a good correlation between results on the effect of chronic CORT treatment on PPE mRNA levels in intact rats, obtained from dot blots and in situ hybridization. Results from this study suggest that glucocorticoids are required for the maintenance of basal PPE mRNA levels in most regions of the rat forebrain. There is, however, considerable regional heterogeneity in the effect of glucocorticoid treatment on PPE mRNA levels in adrenalectomized and intact rats. Increased PPE mRNA levels in response to high circulating levels of glucocorticoids, e.g. in stress, may have important pathophysiological consequences.

A reexamination of the effects of intracerebroventricular glucocorticoids in adrenalectomized rats

Several investigators have reported that many of the behavioral and metabolic effects of ADX can be reversed by appropriate levels of glucocorticoids administered either peripherally or centrally. The present studies were conducted to offer a comparison of the effects of orally administered corticosterone (CORT) with ICV glucocorticoids [CORT, CORT acetate, or dexamethasone (DEX)]. Of particular interest were the effects of glucocorticoid treatment on body weight gain and on macronutrient self-selection. Adult male Sprague-Dawley rats were fitted with ICV cannulae and either bilaterally ADX or given sham operations. In the first experiment, ADX animals were initially treated systemically with CORT (20 μg/ml in their drinking water). After a wash-out period during which no steroids were administered, ADX rats were given daily ICV CORT injections (100 μg/day in 10 μl). Systemic CORT treatment promotes weight gain and normal food choice patterns in ADX rats. ICV injections failed to promote weight gain in ADX rats, and daily injection of the vehicle promoted a weight loss in sham-operated controls. Four additional experiments were conducted. ADX, glucocorticoidtreated animals and ADX, vehicle-treated controls as well as sham-operated, vehicle-treated controls were used to assess the effects of both steroid and vehicle on body weight gain and dietary selection patterns. ADX ICV-glucocorticoid-treated animals typically failed to gain weight at the rate observed when ADX rats are treated with CORT systemically. Under one condition, ADX-CORT-treated animals gained weight at a rate comparable to untreated controls, but their ICV-injected control group failed to gain weight. These results are consistent with the hypothesis that glucocorticoids act principally to modify metabolism, and only secondarily have effects on the central control of appetite.

Glucocorticoid inhibition of inflammation-induced metallothionein synthesis in mouse liver

The effects of glucocorticoid treatment on the induction of hepatic metallothionein (MT) during inflammation initiated by turpentine oil (TUR) or endotoxin (LPS) were studied in mice. The administration of TUR increased concentrations of hepatic MT as well as that of plasma fibrinogen. Although hepatic MT was modestly induced by dexamethasone (DEX) alone, pretreatment with DEX (12.5 to 100 mg/kg, sc) inhibited the increases both in hepatic MT and in plasma fibrinogen from a subsequent dose of TUR 6 hr after DEX administration. The concentration of hepatic MT in the DEX-pretreated (25 mg/kg) group was higher than that in the nonpretreated group 4 hr after administration of TUR, but after 24 hr, the MT concentration in the DEX-pretreated group was inhibited to 20% of that in the nonpretreated group. These inhibitory effects were also observed by prednisolone (PRE) but not by salicylic acid. The inhibitory effect of DEX on the induction of MT synthesis during inflammation was observed after administration of the exudate obtained from inflamed tissue. When inflammation was initiated by an injection of LPS as well as TUR, pretreatment of either DEX or PRE inhibited the increase of hepatic MT. Pretreatment of DEX did not affect the induction of hepatic MT synthesis by cadmium. In contrast to inflammation initiated by TUR or LPS, pretreatment of DEX caused an additive increase of hepatic MT concentration after administration of zinc. These results suggest that glucocorticoids, despite being direct inducers of MT, inhibit the induction of MT synthesis during inflammation by the suppression of cytokine production.

Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat

Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0.85 mg; medium dose, 1.7 mg; high dose, 3.4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 microgram human GHRH(1-29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506.0 +/- 68.5 micrograms/l), peak GH levels were enhanced by the low dose (704.4 +/- 47.8 micrograms/l, P less than 0.05), unaltered by the medium dose (543 +/- 65.8 micrograms/l) and suppressed by the high dose (312.7 +/- 55.2 micrograms/l, P less than 0.05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P less than 0.01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00-12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30-14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 microgram human GHRH(1-29) with samples taken at 5, 10, 20 and 40 min following stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of glucocorticoid receptors in human mononuclear cells: Effects of glucocorticoid treatment, cushing's disease and ketoconazole

Glucocorticoid receptors (GcR) were determined by a whole cell assay in human mononuclear leukocytes (hMNL) from control subjects, patients receiving glucocorticoid therapy for systemic diseases and Cushing's disease patients with or without ketoconazole therapy. Prolonged corticosteroid treatment resulted in down-regulation of GcR, while the mean level of GcR in Cushing's disease was normal. In this group, however, receptor levels and morning plasma cortisol values showed a negative correlation, indicating a subtle down-regulatory effect. Furthermore, GcR were unaltered after these patients received ketoconazole, in spite of a marked reduction in morning plasma cortisol and urinary free cortisol. We also observed that ketoconazole was a weak competitor of GcR in intact cells, although it significantly inhibited [ 3H]dexamethasone binding in cytosolic preparations from rat tissues. The results suggested that GcR in hMNL are down-regulated by synthetic steroids given in vivo, but they showed very mild down-regulation in hypercortisolemic patients suffering from Cushing's disease. Finally, we did not observed either up-regulation or antagonism of GcR by ketoconazole treatment, at the time that cortisol levels of patients with Cushing's disease were reduced. This indicates that the beneficial effects of ketoconazole in Cushing's disease are due to adrenal cortisol suppression and not to interaction with GcR of target cells, and that the process of GcR regulation in hMNL is a complex phenomenon awaiting further elucidation.

Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs

This study investigates the effect of glucocorticoid treatment on the relationship between arteriolar PCO2 and cortical prostanoid production and on cerebrovascular responsiveness to elevated CO2 in newborn piglets. The response of pial arteries to hypercapnia (fractional inspired CO2 = 0.035 and 0.07) was studied in 18 anesthetized newborn piglets, 9 of which were pretreated with dexamethasone (2 mg.kg-1.day-1 for 36-48 h). Pial arterioles (77-122 microns diam) were monitored using a closed cranial window and intravital microscopy. Perivascular cerebrospinal fluid (CSF) was sampled from the cortical surface and analyzed for 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) using radioimmunoassay. In the dexamethasone-treated animals the increase in arteriolar diameter to CO2 was diminished by approximately 50% for each respective CO2 concentration vs. the control group. Acute sympathetic denervation did not restore the CO2 dilator response. Dexamethasone did not alter baseline cortical CSF prostanoid concentrations but abolished the CO2-induced increase in CSF prostanoids. The dilator response to exogenously applied prostaglandin E2 was inhibited in dexamethasone-treated animals. However, the dilator response to exogenous adenosine and the contractile response to prostaglandin F2 alpha were not altered in the dexamethasone-treated piglets. The data support the concept that metabolites of arachidonic acid participate in the cerebrovascular response to CO2 and suggest that glucocorticoid treatment may influence cerebrovascular tone via this mechanism.

Surfactant apoprotein in adult rat lung compartments is increased by dexamethasone

The distribution of the major surfactant apoprotein (SP-A) in adult rat lung was determined in order to gain insight into its metabolism, including packaging of SP-A into lamellar bodies. The effect of glucocorticoid treatment on surfactant apoprotein was studied to test whether regulation of surfactant apoprotein genes, which has been described for the fetal lung, can be demonstrated in the adult animal. We measured the amounts of immunoreactive SP-A in several lung tissue compartments and lavage fractions from control animals and from the lungs of rats given dexamethasone for 1 wk. Protein and phospholipids were measured, SP-A was quantitated with a noncompetitive enzyme-linked immunoabsorbent assay (ELISA) and SP-A, SP-B, and SP-C mRNAs were estimated by Northern blotting. We found an 85-fold concentration of SP-A in a lamellar body-rich fraction compared with lung tissue homogenate and we calculated that as much as one-half of all the tissue SP-A might be accounted for by a lamellar body pool. After 1 wk of dexamethasone treatment, there was an increase in adult rat lung SP-A, SP-B, and SP-C mRNA and a substantial increase in tissue and lavage fluid immunoreactive SP-A pools. Lamellar body fraction SP-A content per lung was 1.4-fold higher after dexamethasone, and there was a fivefold increase in the lavage SP-A pool, much of which was inseparable from the alveolar macrophages. We conclude that SP-A is concentrated in the lamellar bodies of type II cells, that dexamethasone treatment increased all surfactant mRNAs, and that it increased SP-A content in adult rat lung.