Dexamethasone Treatment (dexamethasone + treatment)

Distribution by Scientific Domains


Selected Abstracts


Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment

JOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2000
K. Felszeghy
Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 g/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 g/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source]


Dexamethasone alters F-actin architecture and promotes cross-linked actin network formation in human trabecular meshwork tissue

CYTOSKELETON, Issue 2 2005
Abbot F. Clark
Abstract Elevated intraocular pressure is an important risk factor for the development of glaucoma, a leading cause of irreversible blindness. This ocular hypertension is due to increased hydrodynamic resistance to the drainage of aqueous humor through specialized outflow tissues, including the trabecular meshwork (TM) and the endothelial lining of Schlemm's canal. We know that glucocorticoid therapy can cause increased outflow resistance and glaucoma in susceptible individuals, that the cytoskeleton helps regulate aqueous outflow resistance, and that glucocorticoid treatment alters the actin cytoskeleton of cultured TM cells. Our purpose was to characterize the actin cytoskeleton of cells in outflow pathway tissues in situ, to characterize changes in the cytoskeleton due to dexamethasone treatment in situ, and to compare these with changes observed in cell culture. Human ocular anterior segments were perfused with or without 10,7 M dexamethasone, and F-actin architecture was investigated by confocal laser scanning microscopy. We found that outflow pathway cells contained stress fibers, peripheral actin staining, and occasional actin "tangles." Dexamethasone treatment caused elevated IOP in several eyes and increased overall actin staining, with more actin tangles and the formation of cross-linked actin networks (CLANs). The actin architecture in TM tissues was remarkably similar to that seen in cultured TM cells. Although CLANs have been reported previously in cultured cells, this is the first report of CLANs in tissue. These cytoskeletal changes may be associated with increased aqueous humor outflow resistance after ocular glucocorticoid treatment. Cell Motil. Cytoskeleton 60:83,95, 2005. 2004 Wiley-Liss, Inc. [source]


The effects of dexamethasone and prednisolone on pituitary and ovarian function in the mare

EQUINE VETERINARY JOURNAL, Issue 5 2010
R. A. FERRIS
Summary Reasons for performing study: Persistent mating induced endometritis is among the most common causes of infertility in the mare. Recently, improved pregnancy rates have been reported when corticosteroids were administered to ,problem mares' specifically, to modulate the post mating inflammatory response; however, the effect of treatment on pituitary and ovarian function requires further study. Objectives: To evaluate the effects of prolonged treatment with glucocorticoids on pituitary and ovarian function. Methods: Eighteen cycling Quarter Horse mares in early oestrus were assigned randomly to one of 3 treatment groups: dexamethasone 0.05 mg/kg bwt i.v. twice a day, prednisolone 0.5 mg/kg per os twice a day, or placebo for 5 days. Mares were examined by ultrasound daily to evaluate reproductive function. Blood samples were collected daily to measure luteinising hormone (LH), progesterone and cortisol levels. Results: Dexamethasone treatment caused greater (P<0.05) suppression of endogenous cortisol concentration (9.4 1.1 ng/ml) compared to prednisolone- (41.9 4.0 ng/ml) or placebo-treated mares (32.4 3.8 ng/ml). After 24 h, mares treated with dexamethasone exhibited lower uterine oedema scores than prednisolone- or placebo-treated mares. An ovulation rate of 40% was observed in dexamethasone-treated mares (2/5) compared to 83% for prednisolone (5/6) and 100% for placebo-treated (6/6) mares. An absence of a LH surge was noted in 3 of 5 dexamethasone-treated mares and one of 6 prednisolone-treated mares. Conclusions: Repeated administration of dexamethasone to mares in oestrus is associated with decreased uterine oedema, suppression of LH and a high rate of ovulation failure. It is recommended that dexamethasone treatment is limited to only 1 or 2 days and that a lower dose is considered in the management of persistent mating induced endometritis to avoid potential adverse affects on reproductive function. [source]


Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation

THE JOURNAL OF PHYSIOLOGY, Issue 2 2002
Andrew J. W. Fletcher
This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 1 dGA, fetuses were infused with dexamethasone (2.06 0.13 ,g kg,1 h,1i.v.; n= 13) or saline (n= 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 1 (pre-infusion), 126 1 (during infusion) and 128 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 0.12 mmHg (ml min,1),1 (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment. [source]


A neuro-Behcet's lesion in oculomotor nerve nucleus

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2003
M. D. Aydin
Objective , Fascicular oculomotor nerve involvement is occasionally seen in Behcet's disease, but nuclear involvement is very rare. Case presentation , A 25-year-old woman presented with the Behcet's symptoms and the left eye problems. Physical examination revealed muco-cutaneous lesions, eyelid ptosis, mydriasis, upward and medial gaze palsy and lateral deviation on the left eye. Serologic tests were positive. An inflammatory lesion was detected in the left oculomotor nerve nucleus on magnetic resonance imaging. Neuro-Behcet's disease was considered the most likely diagnosis. Result , Dexamethasone treatment was ordered. Muco-cutaneal lesions, laboratory abnormalities were normalized after 1 year; but oculomotor nerve palsy persisted in spite of improvement in radiological findings. Conclusion , Clinical signs of oculomotor nerve palsy may persist despite the radiological improvement. [source]


Dexamethasone alters F-actin architecture and promotes cross-linked actin network formation in human trabecular meshwork tissue

CYTOSKELETON, Issue 2 2005
Abbot F. Clark
Abstract Elevated intraocular pressure is an important risk factor for the development of glaucoma, a leading cause of irreversible blindness. This ocular hypertension is due to increased hydrodynamic resistance to the drainage of aqueous humor through specialized outflow tissues, including the trabecular meshwork (TM) and the endothelial lining of Schlemm's canal. We know that glucocorticoid therapy can cause increased outflow resistance and glaucoma in susceptible individuals, that the cytoskeleton helps regulate aqueous outflow resistance, and that glucocorticoid treatment alters the actin cytoskeleton of cultured TM cells. Our purpose was to characterize the actin cytoskeleton of cells in outflow pathway tissues in situ, to characterize changes in the cytoskeleton due to dexamethasone treatment in situ, and to compare these with changes observed in cell culture. Human ocular anterior segments were perfused with or without 10,7 M dexamethasone, and F-actin architecture was investigated by confocal laser scanning microscopy. We found that outflow pathway cells contained stress fibers, peripheral actin staining, and occasional actin "tangles." Dexamethasone treatment caused elevated IOP in several eyes and increased overall actin staining, with more actin tangles and the formation of cross-linked actin networks (CLANs). The actin architecture in TM tissues was remarkably similar to that seen in cultured TM cells. Although CLANs have been reported previously in cultured cells, this is the first report of CLANs in tissue. These cytoskeletal changes may be associated with increased aqueous humor outflow resistance after ocular glucocorticoid treatment. Cell Motil. Cytoskeleton 60:83,95, 2005. 2004 Wiley-Liss, Inc. [source]


The effects of dexamethasone and prednisolone on pituitary and ovarian function in the mare

EQUINE VETERINARY JOURNAL, Issue 5 2010
R. A. FERRIS
Summary Reasons for performing study: Persistent mating induced endometritis is among the most common causes of infertility in the mare. Recently, improved pregnancy rates have been reported when corticosteroids were administered to ,problem mares' specifically, to modulate the post mating inflammatory response; however, the effect of treatment on pituitary and ovarian function requires further study. Objectives: To evaluate the effects of prolonged treatment with glucocorticoids on pituitary and ovarian function. Methods: Eighteen cycling Quarter Horse mares in early oestrus were assigned randomly to one of 3 treatment groups: dexamethasone 0.05 mg/kg bwt i.v. twice a day, prednisolone 0.5 mg/kg per os twice a day, or placebo for 5 days. Mares were examined by ultrasound daily to evaluate reproductive function. Blood samples were collected daily to measure luteinising hormone (LH), progesterone and cortisol levels. Results: Dexamethasone treatment caused greater (P<0.05) suppression of endogenous cortisol concentration (9.4 1.1 ng/ml) compared to prednisolone- (41.9 4.0 ng/ml) or placebo-treated mares (32.4 3.8 ng/ml). After 24 h, mares treated with dexamethasone exhibited lower uterine oedema scores than prednisolone- or placebo-treated mares. An ovulation rate of 40% was observed in dexamethasone-treated mares (2/5) compared to 83% for prednisolone (5/6) and 100% for placebo-treated (6/6) mares. An absence of a LH surge was noted in 3 of 5 dexamethasone-treated mares and one of 6 prednisolone-treated mares. Conclusions: Repeated administration of dexamethasone to mares in oestrus is associated with decreased uterine oedema, suppression of LH and a high rate of ovulation failure. It is recommended that dexamethasone treatment is limited to only 1 or 2 days and that a lower dose is considered in the management of persistent mating induced endometritis to avoid potential adverse affects on reproductive function. [source]


Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009
Edward A. Stadtmauer
Abstract This subset analysis of data from two phase III studies in patients with relapsed or refractory multiple myeloma (MM) evaluated the benefit of initiating lenalidomide plus dexamethasone at first relapse. Multivariate analysis showed that fewer prior therapies, along with ,2 -microglobulin (,2.5 mg/L), predicted a better time to progression (TTP; study end-point) with lenalidomide plus dexamethasone treatment. Patients with one prior therapy showed a significant improvement in benefit after first relapse compared with those who received two or more therapies. Patients with one prior therapy had significantly prolonged median TTP (17.1 vs. 10.6 months; P = 0.026) and progression-free survival (14.1 vs. 9.5 months, P = 0.047) compared with patients treated in later lines. Overall response rates were higher (66.9% vs. 56.8%, P = 0.06), and the complete response plus very good partial response rate was significantly higher in first relapse (39.8% vs. 27.7%, P = 0.025). Importantly, overall survival was significantly prolonged for patients treated with lenalidomide plus dexamethasone with one prior therapy, compared with patients treated later in salvage (median of 42.0 vs. 35.8 months, P = 0.041), with no differences in toxicity, dose reductions, or discontinuations despite longer treatment. Therefore, lenalidomide plus dexamethasone is both effective and tolerable for second-line MM therapy and the data suggest that the greatest benefit occurs with earlier use. [source]


Fetal programming and fetal psychology

INFANT AND CHILD DEVELOPMENT, Issue 1 2010
Peter T. Ellison
Abstract The introduction of the ,fetal programming hypothesis', first in epidemiology, subsequently in a broad range of disciplines concerned with developmental biology, has generated new interest in phenotypic plasticity, the mechanisms that govern it, and its place in evolutionary biology. A number of epidemiological studies link small size at birth, assumed to be a consequence of constrained prenatal energy availability, with adverse effects on the risk of chronic diseases later in life. The cluster of chronic diseases associated with the metabolic syndrome and alterations of glucose metabolism are particularly implicated. Recent evidence suggests that epigenetic modification of gene expression affecting the hypothalamic-pituitary-adrenal (HPA) axis may be involved in these effects. In animal studies epigenetic alteration of HPA axis activity and responsiveness is associated with changes in adult behaviour and stress responsiveness. The potential for similar effects to contribute to psychological and psychiatric outcomes in humans has been explored in a number of contexts, including famine exposure, observed covariance with birth weight, and prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia. While fetal programming effects have now been widely demonstrated across species and human populations, the adaptive significance of these effects is still a matter of debate. Copyright 2010 John Wiley & Sons, Ltd. [source]


Adenovirus-mediated BMP2 expression in human bone marrow stromal cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001
Elizabeth A. Olmsted
Abstract Recombinant adenoviral vectors have been shown to be potential new tools for a variety of musculoskeletal defects. Much emphasis in the field of orthopedic research has been placed on developing systems for the production of bone. This study aims to determine the necessary conditions for sustained production of high levels of active bone morphogenetic protein 2 (BMP2) using a recombinant adenovirus type 5 (Ad5BMP2) capable of eliciting BMP2 synthesis upon infection and to evaluate the consequences for osteoprogenitor cells. The results indicate that high levels (144 ng/ml) of BMP2 can be produced in non-osteoprogenitor cells (A549 cell line) by this method and the resultant protein appears to be three times more biologically active than the recombinant protein. Surprisingly, similar levels of BMP2 expression could not be achieved after transduction with Ad5BMP2 of either human bone marrow stromal cells or the mouse bone marrow stromal cell line W20-17. However, human bone marrow stromal cells cultured with 1 ,M dexamethasone for four days, or further stimulated to become osteoblast-like cells with 50 ,g/ml ascorbic acid, produced high levels of BMP2 upon Ad5BMP2 infection as compared to the undifferentiated cells. The increased production of BMP2 in adenovirus transduced cells following exposure to 1 ,M dexamethasone was reduced if the cells were not given 50 ,g/ml ascorbic acid. When bone marrow stromal cells were allowed to become confluent in culture prior to differentiation, BMP2 production in response to Ad5BMP2 infection was lost entirely. Furthermore, the increase in BMP2 synthesis seen during differentiation was greatly decreased when Ad5BMP2 was administered prior to dexamethasone treatment. In short, the efficiency of adenovirus mediated expression of BMP2 in bone marrow stromal cells appears to be dependent on the differentiation state of these cells. J. Cell. Biochem. 82: 11,21, 2001. 2001 Wiley-Liss, Inc. [source]


Altered Mesencephalic Dopaminergic Populations in Adulthood as a Consequence of Brief Perinatal Glucocorticoid Exposure

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2005
S. McArthur
Abstract Early exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological ,programming' are unclear. This study tested the hypothesis that inappropriate exposure to glucocorticoid stress hormones (GCs) during critical periods of development permanently alters the mesencephalic dopaminergic populations in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Using a rat model, the synthetic GC dexamethasone was added to the maternal drinking water during gestational days 16,19 or over the first week of postnatal life. In adulthood, the effects upon tyrosine hydroxylase immunopositive (TH+) cell numbers in the midbrain, and monoamine levels in the forebrain, of the adult offspring were assessed and compared with control offspring whose dams received normal drinking water. In the VTA, both prenatal and postnatal dexamethasone treatment increased TH+ cell numbers by approximately 50% in males and females. Although prenatal dexamethasone treatment also increased TH+ cell numbers in the SNc by 40,50% in males and females, postnatal treatment affected females only by increasing TH+ cell numbers by approximately 30%. In comparison, similar changes were not detected in the monoamine levels of the dorsolateral striatum, nucleus accumbens or infralimbic cortex of either males or females, which is a feature likely to reflect adaptive changes in these pathways. These studies demonstrate that the survival or phenotypic expression of VTA and SNc dopaminergic neurones is profoundly influenced by brief perinatal exposure to GCs at times when endogenous levels are normally low. These findings are the first to demonstrate permanent changes in the cytoarchitecture within midbrain dopamine nuclei after perinatal exposure to stress hormones and implicate altered functionality. Thus, they have significance for the increasing use of GCs in perinatal medicine and indicate potential mechanisms whereby perinatal distress may predispose to the development of a range of psychiatric conditions in later life. [source]


Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment

JOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2000
K. Felszeghy
Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 g/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 g/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source]


Beer But Not Wine, Hard Liquors, or Pure Ethanol Stimulates Amylase Secretion of Rat Pancreatic Acinar Cells In Vitro

ALCOHOLISM, Issue 9 2009
Andreas Gerloff
Background:, In contrast to pure ethanol, the effect of alcoholic beverages on the exocrine pancreas is greatly unknown. Besides ethanol, alcoholic beverages contain numerous nonalcoholic constituents which might have pathophysiological effects on the pancreas. The aim of the present study was to investigate whether some commonly used alcoholic beverages and pure ethanol influence the main function of rat pancreatic acinar cells, i.e., enzyme output in vitro. Methods:, Rat pancreatic AR4-2J cells were differentiated by dexamethasone treatment for 72 hours and freshly isolated pancreatic acini were prepared from Sprague,Dawley rats using collagenase digestion. After incubation of cells in the absence or presence of 1 to 10% (v/v) beer (containing 4.7% v/v ethanol), 10% (v/v) wine (containing 10.5 to 12.5% v/v ethanol), 10% (v/v) hard liquor (such as whisky, rum, and gin), or of the corresponding ethanol concentrations (4.03 to 80.6 mM) for 60 minutes, protein secretion was measured using amylase activity assay. Results:, Incubation of AR4-2J cells with beer caused a dose-dependent stimulation of basal amylase secretion that was significant at doses of beer above 0.5% (v/v). Stimulation with 10% (v/v) beer induced 92.7 25.2% of maximal amylase release in response to the most effective cholecystokinin (CCK) concentration (100 nM). In contrast, ethanol (up to 80.6 mM) did neither stimulate nor inhibit basal amylase release. Lactate dehydrogenase measurement after treatment of AR4-2J cells with beer for 24 hours indicated that the increase of amylase release was not due to cell membrane damage. Wine and hard liquor had no effect on basal amylase secretion neither diluted to the ethanol concentration of beer nor undiluted. In freshly isolated rat pancreatic acinar cells beer dose-dependently stimulated amylase secretion in a similar manner as in AR4-2J cells. Conclusions:, Our data demonstrate that beer dose-dependently increases amylase output. Since neither ethanol nor the other alcoholic beverages tested caused stimulation of amylase release, our findings indicate that nonalcoholic constituents specific for beer are responsible for this increase. These as yet unknown compounds have to be identified and considered in further studies of ethanol-induced pathological and functional changes of the pancreas. [source]


Beer-Induced Pancreatic Enzyme Secretion: Characterization of Some Signaling Pathways and of the Responsible Nonalcoholic Compounds

ALCOHOLISM, Issue 9 2009
Andreas Gerloff
Background:, Various alcoholic beverages have different effects on pancreatic enzyme secretion in vivo and in vitro. Recently we demonstrated that beer dose-dependently induces amylase release of rat pancreatic acinar cells, whereas pure ethanol and other alcoholic beverages have no effect. The aims of this study were to: (1) investigate the involved signaling pathways in the beer-induced enzyme secretion of rat pancreatic acinar cells and (2) characterize the responsible nonalcoholic compounds from beer. Methods:, Rat pancreatic AR4-2J cells were differentiated by dexamethasone treatment for 72 hours. After incubation of cells with 1 to 10% (v/v) beer (containing 4.7% v/v ethanol) in the absence or presence of the maximal effective concentration of cholecystokinin (CCK) (100 nM) for 60 minutes, protein secretion was measured using amylase activity assay. To study the involved signaling pathways, cells were pretreated with selective inhibitors or the fluorescent dye Fura2/AM for 15 and 30 minutes, respectively. To characterize the responsible compounds, beer was distilled, lyophilized, dialyzed, or treated with proteases prior stimulation of the cells. Extract of barley was prepared by boiling the crop and subsequent filtration. Results:, Stimulation with 5% and 10% beer (v/v) significantly (p < 0.001) increased maximally CCK-induced amylase by 55 25% and 56 37%, respectively. By using selective antagonists, we found that inhibition of phospholipase C (PLC) and inositol 1,4,5-trisphosphate-receptor binding reduced beer-induced amylase release, whereas inhibition of protein kinase C, adenylate cyclase, and protein kinase A had no significant effect. Using the fluorescent Ca2+ indicator Fura-2/AM revealed that beer induces an increase of cytosolic free Ca2+ concentration. Stimulation of AR4-2J cells with preproducts of beer and fermented glucose indicated that the stimulatory substances from beer derived from barley and are not produced during alcoholic fermentation. Furthermore, the stimulants from beer are thermostable, nonvolatile substances with a molecular weight higher than 15 kDa. Conclusions:, Beer-induced enzyme secretion of AR4-2J cells is, at least in part, mediated by the activation of PLC and subsequent Ca2+ release from internal stores. However, the additive effect of beer on CCK-induced amylase release suggests that additional signaling pathways are involved. The yet unknown stimulants of pancreatic enzyme secretion originate from barley and their stimulatory potential is maintained during the process of malting and brewing. [source]


Decreased FOXP3 protein expression in patients with asthma

ALLERGY, Issue 10 2009
S. Provoost
Background:, T-regulatory cells (Treg) are important in balancing immune responses and maintaining peripheral tolerance. Current evidence suggests that asthma is characterized by a relative deficiency in Treg, allowing T helper 2 cells to expand. In this study, we aimed to evaluate circulating Treg, defined by the protein FOXP3, in both control subjects and patients with stable asthma. Methods:, Peripheral blood mononuclear cells (PBMC) of control (n = 14) and asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3 and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and representative cytokines were studied. Results:, In control subjects and asthmatic patients, numbers of peripheral blood CD4+CD25high and CD4+CD25highFOXP3+ T-cells were similar. However, FOXP3 protein expression within CD4+CD25high T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4+CD25high T-cells in glucocorticosteroid-treated patients when compared to steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T-bet, and FOXP3/RORc2. Conclusion:, Asthmatic patients have decreased FOXP3 protein expression within their CD4+CD25high Treg. Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4+CD25high T-cell population. [source]


Subhypnotic propofol infusion plus dexamethasone is more effective than dexamethasone alone for the prevention of vomiting in children after tonsillectomy

PEDIATRIC ANESTHESIA, Issue 9 2008
ALI FUAT ERDEM MD
Summary Background:, Postoperative vomiting (POV) is a common complication after tonsillectomy. Dexamethasone is known to decrease postsurgical vomiting. In this study, we compared the effects of dexamethasone alone to dexamethasone plus propofol on postoperative vomiting in children undergoing tonsillectomy. Methods:, In a randomized double-blinded study, we evaluated 80 healthy children, aged 4,12 years, who underwent tonsillectomy with or without adenoidectomy. After anesthesia was induced by inhalation of sevoflurane, 0.15 mgkg,1 dexamethasone and 2 ,gkg,1 fentanyl was administered i.v. to all patients. The patients in the dexamethasone plus propofol group received 1 mgkg,1 propofol before intubation and continuously after intubation at a rate of 20 ,gkg,1min,1 until the surgery was completed. Data for postoperative vomiting were grouped into the following time periods: 0,4 and 4,24 h. Data were analyzed using a Student's t -test and chi-squared analysis. Results:, The percentage of patients exhibiting a complete response (defined as no retching or vomiting for 24 h) increased from 37.5% in the dexamethasone-alone group to 75% in the dexamethasone plus propofol group (P = 0.001). Twenty-two patients (55%) in the dexamethasone-alone and nine patients (22.5%) in the dexamethasone plus propofol groups experienced vomited during 0,4 h (P = 0.003). Eight patients in the dexamethasone-alone group and three patients in the dexamethasone plus propofol group received ondansetron as a rescue antiemetic during the postoperative period. Conclusion:, For children undergoing tonsillectomy, intraoperative subhypnotic propofol infusion combined with dexamethasone treatment provides a better prophylaxis against postoperative vomiting than does dexamethasone alone. [source]


Genome-wide analyses of the transcriptomes of salicylic acid-deficient versus wild-type plants uncover Pathogen and Circadian Controlled 1 (PCC1) as a regulator of flowering time in Arabidopsis

PLANT CELL & ENVIRONMENT, Issue 1 2010
SILVIA SEGARRA
ABSTRACT Salicylic acid (SA) has been characterized as an activator of pathogen-triggered resistance of plants. SA also regulates developmental processes such as thermogenesis in floral organs and stress-induced flowering. To deepen our knowledge of the mechanism underlying SA regulation of flowering time in Arabidopsis, we compared the transcriptomes of SA-deficient late flowering genotypes with wild-type plants. Down- or up-regulated genes in SA-deficient plants were screened for responsiveness to ultraviolet (UV)-C light, which accelerates flowering in Arabidopsis. Among them, only Pathogen and Circadian Controlled 1 (PCC1) was up-regulated by UV-C light through a SA-dependent process. Moreover, UV-C light-activated expression of PCC1 was also dependent on the flowering activator CONSTANS (CO). PCC1 gene has a circadian-regulated developmental pattern of expression with low transcript levels after germination that increased abruptly by day 10. RNAi plants with very low expression of PCC1 gene were late flowering, defective in UV-C light acceleration of flowering and contained FLOWERING LOCUS T (FT) transcript levels below 5% of that detected in wild-type plants. Although PCC1 seems to function between CO and FT in the photoperiod-dependent flowering pathway, transgenic plants overexpressing a Glucocorticoid Receptor (GR)-fused version of CO strongly activated FT but not PCC1 after dexamethasone treatment. [source]


Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase response

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2009
Daniel E. Butz
The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3,h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4,5 delta values lower than those of the control animals by 2.5,h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright 2009 John Wiley & Sons, Ltd. [source]


Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation

THE JOURNAL OF PHYSIOLOGY, Issue 2 2002
Andrew J. W. Fletcher
This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 1 dGA, fetuses were infused with dexamethasone (2.06 0.13 ,g kg,1 h,1i.v.; n= 13) or saline (n= 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 1 (pre-infusion), 126 1 (during infusion) and 128 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 0.12 mmHg (ml min,1),1 (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment. [source]


Composite Tissue Vasculopathy and Degeneration Following Multiple Episodes of Acute Rejection in Reconstructive Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
J. V. Unadkat
Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of ,composite tissue vasculopathy and degeneration (CTVD)' in CTA. [source]


Curcumin differentially regulates TGF-,1, its receptors and nitric oxide synthase during impaired wound healing

BIOFACTORS, Issue 1-2 2002
Haresh Mani
Abstract Wound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors of which transforming growth factor-beta (TGF-,) is one of the most important. Nitric oxide is also an important factor in healing and its production is regulated by inducible nitric oxide synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane), a natural product obtained from the plant Curcuma longa, enhances cutaneous wound healing in normal and diabetic rats. In this study, we have investigated the effect of curcumin treatment by topical application in dexamethasone-impaired cutaneous healing in a full thickness punch wound model in rats. We assessed healing in terms of histology, morphometry, and collagenization on the fourth and seventh days post-wounding and analyzed the regulation of TGF-,1, its receptors type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly accelerated healing of wounds with or without dexamethasone treatment as revealed by a reduction in the wound width and gap length compared to controls. Curcumin treatment resulted in the enhanced expression of TGF-,1 and TGF-, tIIrc in both normal and impaired healing wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed an enhanced expression of TGF-,1 mRNA in curcumin treated wounds as evidenced by in situ hybridization. However, enhanced expression of TGF-, tIrc by curcumin treatment observed only in dexamethasone-impaired wounds at the 7th day post-wounding. iNOS levels were increased following curcumin treatment in unimpaired wounds, but not so in the dexamethasone-impaired wounds. The study indicates an enhancement in dexamethasone impaired wound repair by topical curcumin and its differential regulatory effect on TGF-,1, it's receptors and iNOS in this cutaneous wound-healing model. [source]


Effect of dexamethasone on neutrophil metabolism

CELL BIOCHEMISTRY AND FUNCTION, Issue 2 2003
Carolina Garcia
Abstract The effect of dexamethasone on glucose and glutamine metabolism was investigated. The consumption and oxidation of glucose and glutamine, and the production of glutamate and lactate were determined in neutrophils cultured for 3,h in the presence of dexamethasone. The activities and expression of glucose-6-phosphate dehydrogenase (G6PDH) and phosphate-dependent glutaminase were also determined under the same conditions. Addition of dexamethasone to the culture medium caused a significant increase of glucose consumption at 0.5,,m (123.9%) and 1.0,,m (78.3%) concentrations. In spite of this, however, glucose oxidation remained unchanged. The glucocorticoid did not change glutamine consumption but caused a significant increase of glutamate production and did not alter glutamine oxidation. Dexamethasone-treated neutrophils had a significant decrease of G6PDH activity and expression in particular at 1.0,,m concentration. Phosphate- dependent glutaminase activity was also decreased (about 34%) by dexamethasone treatment. A similar effect was observed on glutaminase expression as indicated by RT-PCR analysis. Thus, the effect of dexamethasone on neutrophil metabolism was particularly noticeable with respect to G6PDH and glutaminase activities where a decrease in the respective mRNA levels was demonstrated. Copyright 2002 John Wiley & Sons, Ltd. [source]


Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea-pigs

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2004
E. A. Leick-maldonado
Abstract Background Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti-inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen-induced chronic airway inflammation in guinea-pigs (GP). Methods GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol. Results Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025). Conclusion Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration. [source]


An open randomized controlled trial of desmopressin and pulse dexamethasone as adjunct therapy in patients with pulmonary involvement associated with severe leptospirosis

CLINICAL MICROBIOLOGY AND INFECTION, Issue 8 2010
K. Niwattayakul
Clin Microbiol Infect 2010; 16: 1207,1212 Abstract Pulmonary involvement in leptospirosis is emerging as a common complication of severe leptospirosis. A prospective randomized controlled trial of desmopressin or high-dose (pulse) dexamethasone as adjunctive therapy in 68 patients with pulmonary involvement associated with severe leptospirosis was conducted between July 2003 and October 2006 at five hospitals in Thailand. There were 23 patients in the desmopressin group, 22 in the pulse dexamethasone group, and 23 in a control group who received standard critical care alone. The diagnosis of leptospirosis was confirmed in 52 patients (77%). There were 15 deaths (22%), of which eight patients received desmopressin, four patients received pulse dexamethasone, and three patients received critical care alone (p 0.19). Eight patients with confirmed leptospirosis died (five patients in the desmopressin group, one in the pulse dexamethasone group and two in the control group). The mortality was not significantly different in the desmopressin group or pulse dexamethasone group compared to the control group in both intention-to-treat patients, and in patients with confirmed leptospirosis. There were no serious events associated with desmopressin treatment, although pulse dexamethasone treatment was associated with a significant increase in nosocomial infection. The results of logistic regression analysis revealed that serum bilirubin level was the only significant risk factor associated with mortality (OR 0.759, 95% CI 0.598,0.965, p 0.024). The results obtained in the present study do not support the use of either pulse dexamethasone or desmopressin as adjunct therapy for pulmonary involvement associated with severe leptospirosis. [source]


Effects of short-term dexamethasone treatment on collagen synthesis and degradation markers in preterm infants with developing lung disease

ACTA PAEDIATRICA, Issue 5 2003
T Saarela
Aim: To assess the effects of dexamethasone treatment on collagen turnover in preterm infants. Methods: The serum concentrations of the amino-terminal propeptide of type I and III procollagens (PINP and PIIINP), which reflect rates of type I and III collagen synthesis, respectively, and the carboxyterminal telopeptide of type I procollagen (ICTP), which reflects the rate of type I collagen degradation, were monitored in 13 preterm infants receiving dexamethasone and 13 matched control infants without glucocorticoid treatment for a total period of 12 mo. Dexamethasone was started at a median age of 12 d and continued at tapering doses for a median total duration of 10 d. Blood samples were taken immediately after birth, at 7, 14 and 28 d of age and at 2, 3, 6, 9 and 12 mo. The same markers were also measured just before the initiation of dexamethasone and on days 1, 3, and 7 of treatment. Results: A striking decrease in all of the markers was already observed in every case on day 1 of dexamethasone, the suppression being greatest on day 3 and still considerable on day 7. The percentages from the pretreatment levels recorded on days 1, 3 and 7 were: for PINP 51, 26 and 45%; for PIIINP 63, 44% and 52%; and for ICTP 64, 41 and 51%. A rebound rise in PINP levels was seen in dexamethasone-treated infants, the levels exceeding those of the controls at 3 and 6 mo of age. A similar phenomenon was noted concerning PIIINP at 3 mo. The levels settled down at 9 and 12 mo. Conclusion: Dexamethasone causes an immediate, inevitable, deep suppression of type I and III collagen synthesis and also type I collagen degradation. This should be taken into consideration, e.g. when assessing for the indications for steroid treatment in sick preterm infants and its dosing and duration. [source]


Body composition in infants with chronic lung disease after treatment with dexamethasone

ACTA PAEDIATRICA, Issue 7 2002
RJ Bolt
The aim of this study was to study the effect of chronic lung disease (CLD) and dexamethasone treatment on body composition in preterm infants (birthweight > 1500g). In addition, anthropo-metric measurement of body composition were compared with dual-energy X-ray absorptiometry (DXA). Fourteen preterm infants with CLD and a comparison group of 18 preterm infants were studied until 3 mo corrected age. CLD infants received approximately 20 kcal kg -1 per day extra nutritional intake during dexamethasone treatment until term. At term no differences were found between CLD and no CLD infants for percentage bone mass (1.4 0.2 vs 1.4 0.1%), fat mass (18.7 4.5 vs 17.4 3.5%), lean body mass (79.9 4.6 vs 81.2 3.5%) or bone mineral density (0.15 0.02 vs 0.15 0.01%). At 3 mo corrected age both groups were also similar for bone mass (1.6 0.1 vs 1.6 0.2%), fat mass (22.6 5.5 vs 24.5 5.7%), lean body mass (75.8 5.7 vs 74.0 5.8%) and bone mineral density (0.20 0.02 vs 0.20 0.01%). All anthropometric measurements showed a high correlation with body composition. However, calculated fat mass was 56.7 8.8% lower than fat mass measured with DXA. Conclusion: Body composition at term and 3 mo corrected age in preterm infants treated with dexamethasone for CLD, who received extra caloric intake until term, did not differ from that in preterm infants without CLD. [source]


Changes in serum leptin concentration after corticosteroid treatment in preterm infants

ACTA PAEDIATRICA, Issue 6 2002
PC Ng
The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic-pituitary-adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (Td-pre), 3 wk after commencement of the drug (Td-end) and 2 wk after dexamethasone treatment had been stopped (Td-post). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (Twk,2), 5 (Twk,5) and 7 (Twk,7) wk of postnatal age. Serum leptin and insulin at Td,end were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (Td,pre) levels in the corticosteroid group (p > 0.0001 for leptin and insulin; p > 0.05 and p > 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (Twk,5) and 7 (Twk,7) did not differ significantly from their respective levels at week 2 (Twk,2) in the non-treatment group. Conclusion: The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the "adipoinsular" and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates. [source]