Effects Of Dexamethasone Administration Research Articles

The effects of dexamethasone administration on physiological, behavioral, and production parameters in dairy cows after a difficult calving.

Dairy cows are predisposed to diseases during the postpartum period. Dystocia has been associated with increased risk for disease, which is likely the result of increased tissue trauma and stress during the prolonged parturition. To attenuate the inflammatory response seen in dystocic animals and improve well-being, we assessed the effects of a glucocorticoid, dexamethasone administered within 12 h after calving. Dystocia was defined as a difficult birth resulting in a prolonged calving (≥70 min after the amniotic sac appears) and was monitored through 3 video cameras in the close-up dry-cow pen. Cows meeting the dystocia definition were randomly assigned to receive a single intramuscular injection of either dexamethasone (DEX; 0.1 mg/kg of body weight; n = 43) or saline (CON, n = 44) within 12 h following a dystocic calving. Serum haptoglobin, blood β-hydroxybutyrate (BHB) concentrations, body temperature, and several behaviors were measured for the first 7 d postpartum. Additionally, milk production and components for the first 120 d were recorded. Using a mixed model, the fixed effects of treatment, parity, calving assistance, and time, along with 2- and 3-way interactions, were analyzed with cow as a random effect. We observed that primiparous DEX cows had greater serum haptoglobin concentrations on d 3 and d 7 postpartum compared with primiparous CON cows. There was no difference between treatment groups for blood BHB concentrations and body temperature. Behavior was altered between treatments, with DEX cows having reduced activity for the first week postpartum, as well as less restlessness and increased lying times on some of the days following calving. Treatment interacted with time for milk yield, such that DEX cows produced 2.7 kg/d less milk than CON cows for the first month following calving. The administration of dexamethasone resulted in changes in behavioral measurements, which could suggest a reduction in discomfort; however, due to the reduction in milk yield for the first month following calving, DEX administration may not be applicable for typical farm use. Additional research is needed to investigate treatments for cows experiencing dystocia without detrimental effects on milk yield.

Environmental enrichment modulates silent information regulator 1 (SIRT1) activity to attenuate central presbycusis in a rat model of normal aging.

Age-related hearing loss (ARHL) is sensory impairment in the elderly. This study aimed to identify a critical molecular mechanism that can maintain young phenotypes. We focused on the effect of exposure to environmental enrichment (EE) for 12weeks in the central auditory pathway and limbic system of aged rats. The effects of EE were compared with the effects of dexamethasone administration. We found that in 74-week-old rats hearing function was significantly reduced and the number of neuronal specific nuclear protein (NeuN)-positive cells was decreased by 10-15% in the auditory cortex, amygdala, and hippocampus. EE exposure did not significantly affect the number of neurons, but DX administration significantly decreased their numbers in the amygdala compared with untreated aged rats. Both treatments reduced inducible nitric oxide synthase (iNOS) expression in the auditory pathway and limbic system. Exposure to EE significantly increased silent information regulator 1 (SIRT1) expression and activity, and nicotinamide phosphoribosyltransferase (NAMPT) concentration. In this study, the exposure to EE resulted in attenuated age-related hearing loss accompanied by reduction of iNOS expression and increase SIRT1 activity and NAMPT level. These data showed that EE may be a potential therapeutic to prevent ARHL.

Antinociceptive and anti-inflammatory activities of a standardizedextract of bis-iridoids from Pterocephalus hookeri

Ethnopharmacological relevancePterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before. Aim of the studyThis study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis. Materials and methodsThe analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied. ResultsBCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter. ConclusionThe results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Relationship of Glucocorticoid Receptor Expression in Peripheral Blood Mononuclear Cells and the Cochlea of Guinea Pigs and Effects of Dexamethasone Administration

BackgroundGlucocorticoids (GCs) are widely used to treat sudden sensorineural hearing loss (SSNHL) and significantly improve hearing. However, GC insensitivity has been observed in some patients of SSNHL.ObjectiveTo study the correlation between GR expression in peripheral blood mononuclear cells (PBMCs) and in the cochlea of guinea pigs at mRNA and protein levels.MethodsOne group of guinea pigs received dexamethasone (10 mg/kg/day) intraperitoneally for 7 consecutive days (dexamethasone group), and another group of guinea pigs received normal saline (control group). Real time PCR and Western blotting were used to detect the expression of GR mRNA and GR protein in PBMCs and the cochleae.ResultsThe GR mRNA and GR protein were detected in both PBMCs and the cochlear tissue of guinea pigs. GR mRNA and GR protein levels in PBMCs were positively correlated with those in the cochlea. The expression of GR mRNA and GR protein was significantly increased in the dexamethasone group compared to the control group.ConclusionsLevels of GR mRNA and GR protein in the PBMCs were positively correlated with those in the cochlea of guinea pigs. Systemic dexamethasone treatment can significantly up-regulate GR expression in PBMCs and in the cochlea. Measurement of the GR level in PBMCs could be used as an indicator of GR level in the cochlea.

Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle

To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC). 6 adult Standardbreds. In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance and phosphorylation state (PKB Ser(473) and GSK-3alpha/beta Ser(21/9)), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration. Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state. In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.

Age‐Related Effects of Dexamethasone Administration in Adrenal Zona Reticularis

Suppression of adrenocorticotropic hormone results in reduced adrenal steroid output, adrenocortical cell atrophy, and apoptosis in young rats. To verify such effects during aging, dexamethasone was injected into rats for 3 days at five different ages; at day 4, adrenals and blood were collected for morphologic and corticosterone assay. Adrenal structure was similar at all ages, but in dexamethasone-injected animals there were ultrastructural features of apoptosis and a higher percentage of TUNEL and caspase-3-labeled nuclei and cytoplasm; their corticosterone decreased significantly. In both groups, there was age-related decrease in the percentage of apoptotic cells, significant only in dexamethasone-injected rats. The data suggest that aged adrenocortical cells are less susceptible to the lack of adrenocorticotropic hormone (ACTH), possibly as a result of their decreased functional ability.

Indomethacin, dexamethasone, and intestinal damage in infant rats.

Indomethacin is commonly used in the Neonatal Intensive Care Unit to induce closure of the patent ductus arteriosus and to prevent intraventricular hemorrhage. It is known that indomethacin causes intestinal ulceration in adults, but its effect in infants is less clear. In a preliminary experiment, it was found that the administration of 10 mg/kg/d of indomethacin, a dose that damages the adult rat intestine, had no detrimental effects on newborn suckling rats whereas dexamethasone at 0.25 mg/kg/d caused significant growth failure and villous blunting. It was then hypothesized that the lack of intestinal damage with indomethacin in infants was related to protection given by mother's milk. Subsequent experiments were performed wherein 10 mg/kg/d of indomethacin was provided to infant mother-reared, infant artificially fed, and adult rats. The expression of intestinal cyclooxygenases in the prostaglandin synthetic pathway of control rats was examined to initiate an exploration into a mechanism for the developmental response to indomethacin. Mother-reared and artificially fed infant rats demonstrated resistance to the ulcerogenic effects of indomethacin, in contrast to the adults. A differential presence of cyclooxygenase-1 and cyclooxygenase-2 was not distinctly seen between infancy and adulthood. The results indicate that a varying response to the damaging effects of indomethacin on the intestine occurs during development with the infant being less susceptible than the adult. This differed from the effects of dexamethasone administration, which caused significant intestinal atrophy in the infant rats. The intestinal protection to the effects of indomethacin in infants is not dependent on mother's milk or a developmental difference in the prostaglandin biosynthetic pathway.

Indomethacin, Dexamethasone, and Intestinal Damage in Infant Rats

ABSTRACTBackgroundIndomethacin is commonly used in the Neonatal Intensive Care Unit to induce closure of the patent ductus arteriosus and to prevent intraventricular hemorrhage. It is known that indomethacin causes intestinal ulceration in adults, but its effect in infants is less clear. In a preliminary experiment, it was found that the administration of 10 mg/kg/d of indomethacin, a dose that damages the adult rat intestine, had no detrimental effects on newborn suckling rats whereas dexamethasone at 0.25 mg/kg/d caused significant growth failure and villous blunting. It was then hypothesized that the lack of intestinal damage with indomethacin in infants was related to protection given by mother's milk.MethodsSubsequent experiments were performed wherein 10 mg/kg/d of indomethacin was provided to infant mother‐reared, infant artificially fed, and adult rats. The expression of intestinal cyclooxygenases in the prostaglandin synthetic pathway of control rats was examined to initiate an exploration into a mechanism for the developmental response to indomethacin.ResultsMother‐reared and artificially fed infant rats demonstrated resistance to the ulcerogenic effects of indomethacin, in contrast to the adults. A differential presence of cyclooxygenase‐1 and cyclooxygenase‐2 was not distinctly seen between infancy and adulthood.ConclusionsThe results indicate that a varying response to the damaging effects of indomethacin on the intestine occurs during development with the infant being less susceptible than the adult. This differed from the effects of dexamethasone administration, which caused significant intestinal atrophy in the infant rats. The intestinal protection to the effects of indomethacin in infants is not dependent on mother's milk or a developmental difference in the prostaglandin biosynthetic pathway.

Effects of dexamethasone administration on serum trypsin-like immunoreactivity in healthy dogs

Abstract Objective To determine whether administration of dexamethasone altered serum trypsin-like immunore-activity (TLI) in healthy dogs. Animals 12 healthy dogs. Procedure Dexamethasone (0.25 mg/kg, PO, q 24 h) was administered for 7 days. Serum TLI, α-amylase and alanine aminotransferase (ALT) activities, and urea and creatinine concentrations were determined on days 0, 7, 14, and 21 of the study. Results Serum TLI and ALT activities were significantly increased, and serum α-amylase activity was significantly decreased after administration of dexamethasone for 7 days. However, values obtained on days 14 and 21 were not significantly different from baseline values. Dexamethasone administration was not associated with any significant changes in serum creatinine or urea concentrations. Serum TLI and α-amylase activities were significantly correlated prior to dexamethasone administration. Dogs did not develop clinical signs of pancreatitis. Conclusions and Clinical Relevance Dexamethasone administration was associated with an increase in serum TLI. However, values returned to baseline 7 days after dexamethasone administration was discontinued. Serum TLI may be falsely high in dogs that have been treated with dexamethasone in the week preceding analysis. (Am J Vet Res 1999;60:1357–1359)

Retinoids modulate the binding capacity of the glucocorticoid receptor and its translocation from cytosol to nucleus in liver cells.

The binding capacity (Cmax) of the glucocorticoid hormone receptor (GR) was affected by vitamin A status in rat liver. In rats fed on a vitamin A-overloaded diet as well as in rats administered with retinoic acid (RA) there was an increased ratio Cmax of nuclear GR (expressed as fmol/mg liver): Cmax of cytosolic GR (expressed as fmol/mg liver) while in rats fed on a vitamin A-deficient diet this ratio was decreased. These results suggested that an increased amount of RA, resulting from either metabolization of an increased amount of dietary retinol or RA administration, enhanced the translocation of GR from the cytosolic compartment to the nuclear compartment. Moreover such an increased amount of RA could also induce the observed decreased Cmax of the total GR that we observed. These observations were similar to the well known effects of dexamethasone administration on the properties of GR. It is probable that RA, similarly to dexamethasone treatment, induces a dissociation of the tetrameric form of the cytosolic GR and thus enhances translocation of the monomeric form from cytosol to nucleus and also resulting in an increased proteolytic degradation of the receptor.

The effect of dexamethasone administration on rat intestinal permeability: The role of bacterial adherence

Previous studies have shown that dexamethasone administration to rats results in diminution of biliary secretory immunoglobulin A concentration and alters intestinal barrier function to bacteria. The aims of this study were to examine and characterize the effect of dexamethasone on intestinal permeability and to determine the possible influence of bacterial adherence to the mucosa in this process. Groups of adult Fisher rats were studied, and the effects of dexamethasone administration and bowel decontamination on bacterial adherence and intestinal permeability were determined in various bowel segments. Dexamethasone administration was associated with a significant increase in bacterial adherence to the mucosa, which was most pronounced in the cecum (4.33 +/- 0.2 colony forming units (cfu) (log10) per gram of mucosa for control vs. 6.23 +/- 0.2 for dexamethasone). This was accompanied by significant alterations in intestinal permeability as measured by a decrease in transepithelial electrical resistance (49.5 +/- 4.1 omega.cm2 for control vs. 25.4 +/- 2.5 omega.cm2 for dexamethasone). Dual sodium-mannitol flux analysis showed this defect to be predominantly paracellular. Antibiotic decontamination of the intestine completely abrogated the intestinal permeability defect observed in this model. Bacterial-mucosal cell interactions may be responsible for alterations in intestinal permeability after dexamethasone administration.

Effects of dexamethasone on carnitine metabolism in liver and extrahepatic tissues.

The in vivo effects of dexamethasone administration on liver and extrahepatic tissue carnitine concentrations were assessed in 48-h-starved rats. In heart and kidney, but not in liver, dexamethasone significantly increased total carnitine concentration. Acute (2.5 h) treatment with 2-tetradecylglycidate (TDG), a specific inhibitor of carnitine palmitoyl transferase 1, not only increased total hepatic carnitine concentrations, but also permitted an effect of dexamethasone (a further increase in hepatic carnitine concentration). The results are discussed in terms of acute (substrate-mediated) and chronic (hormonal) control of carnitine turnover.

The effects of dexamethasone administration on EEG sleep in depressed patients

Since DST non-suppression and sleep abnormalities have been shown to co-exist in depressive states, it seems important to examine what effects dexamethasone administration might have on the sleep of depressed patients. Therefore, the effects of 1 mg dexamethasone p.o. administered at 11 p.m. to a group of 12 depressed outpatients was examined. In this series of patients, the hypothesis of no significant changes in sleep continuity, sleep architecture or REM sleep features was confirmed aside from an increase in Stage 2 sleep percent and decrease in Stage 1 REM percent in these patients (both variables stayed in the normal range). It can be concluded that acute administration of dexamethasone does not influence the sleep of depressed patients in a major way.

Effects of dexamethasone administration on hepatic glycogen synthesis and accumulation in adrenalectomized fasted rats.

Adrenalectomized 24-h fasted rats lack the ability to synthesize and accumulate hepatic glycogen. In addition, the ability of liver glycogen synthase to respond to acute glucose administration is muted. The defect has been localized to the level of smooth endoplasmic reticulum-associated synthase phosphatase activity which is greatly reduced in adrenalectomized fasted rat liver. In vivo exposure to dexamethasone increases hepatic glucose output and hepatic glycogen synthesis and accumulation by 2-6 h after administration. Smooth endoplasmic reticulum synthase phosphatase activity is increased, and activation of glycogen synthase is restored. Ambient insulin concentrations are increased by steroid administration and appear to have a role in restoration of the ability to activate glycogen synthase, and consequently to restore the ability to synthesize and accumulate hepatic glycogen.

Effects of changes in serum insulin in response to dexamethasone and adrenalectomy on insulin-sensitive phosphodiesterase in rat fat cells

The effects of dexamethasone administration and adrenalectomy on insulin-sensitive phosphodiesterase were studied in rat fat cells. Isolated fat cells were incubated at 37°C for ten minutes with or without insulin. A crude microsomal fraction prepared by differential centrifugation was used for the determination of phosphodiesterase level. With dexamethasone treatment (400 μg/kg/day) for seven days, specific activity of the enzyme and its sensitivity (ED 50) to insulin were decreased, as was the maximal responsiveness to insulin. Under conditions of adrenalectomy, the specific activity and the sensitivity (ED 50) were increased while the maximal responsiveness to insulin was decreased. Following dexamethasone treatment specific insulin binding was decreased, and after adrenalectomy it increased. These findings were attributed to changes in the number of insulin receptors per cell rather than to changes in affinity. Alterations in insulin sensitivity (ED 50) of the enzyme seemed to be due to alterations in insulin binding to the receptor. The reduction in maximal insulin responsiveness suggested postreceptor defects in both experimental groups. The mechanism related to alterations in the specific activity was not thoroughly clarified; however, serum insulin levels may specifically affect the enzyme activity.