Dexamethasone Treatment Group Research Articles

The establishment of biological reference intervals of neonatal immunologic function in 24-hour newborns in Guangxi Province

Objective To establish biological reference intervals of neonatal T lymphocyte subsets and IgG, IgA, IgM levels in 24-hour newborns in Guangxi. Methods Maternal history and neonatal clinical data were evaluated and recorded.Venous blood samplings were collected within 24 hours of birth and were sent for testing in half an hour.The neonates were divided into the early-preterm, the late-preterm and the term neonates group, 110 cases for each group.The parturients were divided into Dexamethasone treatment group and without Dexamethasone treatment group.Data in neonates and the parturients and the sex were analyzed by SPSS 17.0 software and the biological refe-rence values were calculated. Results The two-sided reference intervals of 95% in the early-preterm group, the late-preterm group and the term neonates group were as follows: CD3+ : 52.07-88.92 g/L, 58.16-90.42 g/L, 56.15-95.67 g/L; CD4+ : 25.20-59.26 g/L, 31.27-72.91 g/L, 28.44-82.66 g/L; CD8+ : 7.30-36.26 g/L, 9.13-38.49 g/L, 11.09-48.99 g/L; CD4+ /CD8+ : 0.34-4.58, 0.34-4.58, 0.32-3.80; CD19+: 3.95-27.59 g/L, 4.04-30.94 g/L, 4.08-38.70 g/L; NK cell: 1.34-6.64 g/L, 2.88-8.92 g/L, 3.07-9.35 g/L; IgA: 0.000 4-0.039 6 g/L, 0.000 0-0.069 0 g/L, 0.000 0-0.069 0 g/L; IgM: 0.001 6-0.158 4 g/L, 0.020 0-0.140 0 g/L, 0.020 0-0.420 0 g/L; IgG: 3.22-10.98 g/L, 1.10-14.62 g/L, 5.00-13.66 g/L.Moreover the cases with Dexamethasone treatment were as follows: the late-preterm infants CD8+ 10.35-40.33 g/L, NK 3.10-9.46 g/L, term NK 6.60-9.50 g/L; those in without Dexamethasone treatment: the late-preterm infants CD8+ 8.42-34.96 g/L, NK 2.94-7.80 g/L, term NK 2.98-8.94 g/L; according to gender, the males in the late-preterm infants CD8+ 8.26-35.66 g/L, term CD3+ 51.90-92.94 g/L; females in the late-preterm infants CD8+ 11.08-40.68 g/L, term CD3+ 61.10-96.14 g/L. Conclusions Testing values of neonatal T lymphocyte subsets and IgG, IgA, IgM levels in 24-hour newborns in Guangxi disperse largely and show some differences among the early-preterm neonates, the late-preterm neonates and the term neonates, and maternal Dexamethasone treatment during pregnancy and gender play a role in neonatal immunity. Key words: Infant, newborn; Immunologic function; T lymphocyte subsets; Immunoglubulin

Early-life stress changes expression of GnRH and kisspeptin genes and DNA methylation of GnRH3 promoter in the adult zebrafish brain

Early-life stress can cause long-term effects in the adulthood such as alterations in behaviour, brain functions and reproduction. DNA methylation is a mechanism of epigenetic change caused by early-life stress. Dexamethasone (DEX) was administered to zebrafish larvae to study its effect on reproductive dysfunction. The level of GnRH2, GnRH3, Kiss1 and Kiss2 mRNAs were measured between different doses of DEX treatment groups in adult zebrafish. Kiss1 and GnRH2 expression were increased in the 200mg/L DEX treated while Kiss2 and GnRH3 mRNA levels were up-regulated in the 2mg/L DEX-treated zebrafish. The up-regulation may be related to programming effect of DEX in the zebrafish larvae, causing overcompensation mechanism to increase the mRNA levels. Furthermore, DEX treatment caused negative impact on the development and maturation of the testes, in particular spermatogenesis. Therefore, immature gonadal development may cause positive feedback by increasing GnRH and Kiss. This indicates that DEX can alter the regulation of GnRH2, GnRH3, Kiss1 and Kiss2 in adult zebrafish, which affects maturation of gonads. Computer analysis of 1.5kb region upstream of the 5′ UTR of Kiss1, Kiss2, GnRH2 and GnRH3 promoter showed that there are putative binding sites of glucocorticoid response element and transcription factors involved in stress response. GnRH3 promoter analysed from pre-optic area, ventral telencephalon and ventral olfactory bulb showed higher methylation at CpG residues located on −1410, −1377 and −1355 between control and 2mg/L DEX-treated groups. Hence, early-life DEX treatment can alter methylation of GnRH3 gene promoter, which subsequently affects gene regulation and reproductive functions.

Effects of glycerin fructose combined with dexamethasone on the expressions of aquaporins-4 and matrix metalloproteinases-9 and neurological function in mice after cerebral hemorrhage

Objective To assess the effects of glycerin fructose combined with dexamethasone on neurological function and the expressions of aquaporins (AQP)-4 and matrix metalloproteinases (MMP)-9 in mice after cerebral hemorrhage. Methods Totally 96 male mice(kunming) were randomly divided into the control group (n=24), the model group (n=24), dexamethasone treatment group (n=24), glycerin fructose combined with dexamethasone treatment group (combination group, n=24). The cerebral hemorrhage model was set up in the last three groups, which were given corresponding drug treatment. Mice in each group were subgrouped into 12 h , 1 d, 3 d and 5 d groups according to the time after treatment (n=6, each group). The neurological function was determined according to the reformed mNSS. The dry and wet weight method was used to the brain water content. RT-PCR technology was used to analysis the expressions of AQP-4 and MMP-9 mRNA in mice brain tissue. Results Each treatment group as compared with model group, mNSS was the highest (F=4.56, P<0.05). the brain water content was the lowest (F=5.38, P<0.05), the mRNA expressions of AQP-4 and MMP-9 was the least in combination Group(F=4.02, F=4.68, P<0.05) Conclusions Dexamethasone may relieve cerebral edema, improve the neural function in mice after brain hemorrhage and protect the brain tissue by regulating the transcriptional expression of AQP-4 and MMP-9. If combined with the high permeability dehydrant glycerin fructose, dexamethasone will further inhibit the progress of neurological impairment and brain edema. Key words: Fructors; Dexamethasone; Cerebral hemorrhage; Aquaporin 4; Matrix metalloproteinase 9

Effect and mechanism of ginsenoside Rg1 as an alcoholic hepatitis treatment in a rat model

To observe the effect of Rgl treatment on prognosis of alcoholic hepatitis using a rat model. Female Sprague-Dawley rats were radomly divided into four groups:unmodeled control, untreated model, Rgl-treated model, and dexamethasone (DXM)-treated model. The model groups were generated by intragastric injection of alcohol. The unmodeled control group was given an equal dosage of normal saline by the same route. After model establishment, the Rg1 treatment group and the DXM treatment group were administered a 120-hour treatment of Rgl or DXM; the unmodeled controls were administered normal saline on the same schedule. All rats were then fasted for 120 hours and venous blood samples were collected for detection of serum aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBil), albumin (Alb), tumor necrosis factor-alpha (TNFat) and interleukin 6 (IL-6). Markers of liver inflammation were measured by immunohistochemistry, western blotting, and real-time quantitative reverse transcription PCR. Fat and apoptosis indices were assessed by hematoxylin-eosin staining and TUNEL assay, respectively. The t-test and F test were used for statistical analyses. The model group showed remarkably more liver steatosis (over one-third of the tissue) than the unmodeled control group, indicating proper establishment of alcoholic liver disease in the modeled rats. The AST, ALT, TBil, and IL-6 levels were significantly higher in the untreated model group than in the Rgl-treated group and the DXM-treated group. The values were significantly different between the Rg1-treated group and the DXM-treated group:ALT, 69.19+/-8.00 U/L vs.102.88+/-5.16 U/L; TBil, 0.36+/-0.07 µmol/L vs.1.20+/-0.18 µmol/L; IL-6, 126.50+/-6.50 U/ml vs.169.19+/-7.68 U/ml; TNFa, 268.31+/-13.19 µg/L vs.318.94+/-7.87 µg/L (all P less than 0.05). Expression of caspase3 and caspase8 was significantly higher in the model group than in the Rgltreated group and the DXM-treated group (both P<0.05). The apoptosis index was significantly lower in the Rgltreated group and the DXM-treated group than in the model group (both P<0.05). The mRNA and protein expression of caspase3, caspase8 and NF-kB were significantly lower in the Rgl-treated group and the DXM-treated group than in the model group (allP less than 0.05), and the levels of all were significantly lower in the Rgl-treated group cornered to the DXM-treated group (all P<0.05). Conehision In rats with alcoholic hepatitis, Rg1 can significantly relieve pathological injury, improve liver function by blocking the apoptotic pathway, and inhibit release of inflammatory cytokines.

Panaxadiol Saponin and Dexamethasone Improve Renal Function in Lipopolysaccharide-Induced Mouse Model of Acute Kidney Injury.

BackgroundAcute kidney injury (AKI) is a serious complication of systemic inflammatory response syndrome (SIRS), which has a high mortality rate. Previous studies showed that panaxadiol saponin (PDS) and Dexamethasone have similar anti-inflammatory properties and protect cardiopulmonary function in lipopolysaccharide (LPS)-induced septic shock rats. In the present study, we investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice.Methods and ResultsMice subjected to LPS (10 mg/kg) treatment exhibited AKI demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P<0.01). However, PDS and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P<0.05). PDS decreased the production and release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by inhibiting the NF-κB signaling pathway, down-regulating inducible nitric oxide synthase protein expression levels and inhibiting oxidative stress. In most anti-AKI mechanisms, PDS and dexamethasone were similar, but PDS are better at inhibition of TNF production, promote SOD activity and inhibition of IKB phosphorylation. In addition, nuclear glucocorticoid receptor expression was markedly enhanced in PDS and Dexamethasone treatment groups. Further research is required to determine whether PDS can combine with the glucocorticoid receptor to enter the nucleus.ConclusionThis study demonstrated that PDS and dexamethasone have similar reverse amelioration for renal functions, and have potential application prospects in the treatment of sepsis-induced AKI.

Inhibition of pulmonary nuclear factor -ΚB and tumor necrosis factor -α expression by diallyl sulfide in rats with paraquat poisoning

To investigate the mechanism of anti-inflammatory effect of diallyl sulfide (DAS) in protection against acute lung injury (ALI) in rats with paraquat poisoning. Eighty male Wistar rats were randomly divided into four groups, namely: control group, model group, dexamethasone (DXM) treatment group, and DAS treatment group, with 20 rats in each group. The model of paraquat poisoning was reproduced by single does of 70 mg/kg given by gavage, while the same volume of normal saline (NS) was given in same manner in control group. 100 mg/kg of DAS, the same volume of NS, or 1 mg/kg DXM injection were given respectively in DAS treatment group, model group, or DXM treatment group intraperitoneally after exposure to paraquat, once a day for 14 days. Five rats in each group were sacrificed at 1, 3, 7, 14 days, respectively. The inferior lobe of right lung was harvested, and the degree of lung injury was observed with hematoxylin and eosin (HE) staining under optical microscope; the upper lobe of right lung was used to determine the lung wet/dry weight (W/D) ratio and for evaluation of the degree of pulmonary edema. The expression of nuclear factor -ΚB (NF-ΚB) in the middle lobe of right lung was assessed with immunohistochemistry. The expression of tumor necrosis factor -α ( TNF-α ) mRNA in the left lung was determined with the reverse transcription-polymerase chain reaction (RT-PCR). (1) The pulmonary structure in control group was found to be intact. However, in the model group there were progressive pathological changes in lung, including marked edema and thickening of alveolar walls, collapse of alveoli, infiltration of inflammatory cells, alveolar wall, and obvious bleeding in the local lung tissue, and formation of transparent membrane in alveolar space. Less infiltration of inflammatory cells and no obvious destruction were found in alveolar structure in the DAS and DXM treatment groups. (2) Lung W/D ratio: lung W/D ratio of model group was apparently higher than that in control group at every time point, and peaking on the 3rd day ( 6.15 ± 0.54 vs. 4.15 ± 2.10, P < 0.05 ), and the ratio of lung W/D of DAS and DXM treatment groups was obviously lower than that in model group at every time point, especially on the 3rd day (3.99 ± 1.26, 4.30 ± 0.70 vs. 6.15 ± 0.54, both P < 0.05), but there was no significant difference between DAS and DXM treatment groups in this regard. (3) The immunocytochemistry analysis revealed minimal NF-ΚBp65 expression in the cell nuclei of the control group, while extensive NF-ΚBp65 expression was found in model group. Minimal NF-ΚBp65 positive expression in the cytoplasm and even less positive expression in the nucleus was found in the DAS and DXM treatment groups, and integral A value was significantly lower in the DAS and DXM treatment groups than that of the model group, especially on the 3rd day [(17.98 ± 0.06 )× 10⁷, (18.53 ± 0.04) × 10⁷ vs. (28.85 ± 0.61) × 10⁷, both P < 0.01], but there was no significant difference between DAS and DXM treatment groups. (4) It was shown by RT-PCR that the expression of TNF-α mRNA in lung tissue of the model group was significantly higher than that in the control group on the 3rd day (gray value: 3.63 ± 0.62 vs. 0.51 ± 0.13, P < 0.05 ). The expression of TNF-α mRNA in lung tissue was significantly decreased in DAS and DXM treatment groups compared with model group ( gray value: 2.49 ± 0.57, 2.02 ± 0.26 vs. 3.63 ± 0.62, both P < 0.05 ), but there was no significant difference between DAS and DXM treated groups. Treatment with an intraperitoneally injection of DAS is capable of attenuate the extent of PQ-induced ALI in rats by alleviating pulmonary edema, inhibiting the expression of NF-ΚB and TNF-α in lung tissue, and ameliorating pathological changes in lung tissue.

Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic renal failure.

The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (P<0.05) and improve renal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.

Comparison of effect of granules and herbs of Bu-Shen-Yi-Qi-Tang on airway inflammation in asthmatic mice

Background Bu-Shen-Yi-Qi-Tang (BSYQT), which is prescribed on the basis of clinical experience, is commonly used in clinics of traditional Chinese medicine (TCM) for asthma treatment. The components of BSYQT include Radix Astragali (RA), Herba Epimedii (HE) and Radix Rehmanniae (RR). The aim of this study was to compare the effect of granules and herbs of BSYQT on airway inflammation in asthmatic mice. Methods Sixty female BALB/c mice were randomly divided into the normal control (NC) group, asthmatic group (A), decoction of granules of BSYQT treatment group (GD), decoction of herbs of BSYQT treatment group (HD), and dexamethasone treatment group (DEX). The mouse asthmatic model was induced by ovalbumin (OVA) sensitization and challenge. GD and HD of BSYQT as well as DEX were prepared and administered by intragastric infusion. Airway hyperresponsiveness (AHR) to methacholine (Mch), lung histopathology analysis, inflammatory mediators in serum (IL-4, IL-5, IL-17A, IFN-γ, and eotaxin) and in lung (IL-4, IL-5, IFN-γ, and eotaxin) were selected for investigation and comparison. Results Both GD and HD treatment could decrease airway resistance (RL) and increase dynamic compliance (Cdyn) to Mch compared with the A group (P &lt;0.05). HD treatment was more effective in RL reduction than Mch at doses of 3.125 and 6.25 mg/ml (P &lt;0.05) and in Cdyn increase at Mch doses of 6.25 and 12.5 mg/ml (P &lt;0.05). There were no marked differences in RL reduction and Cdyn improvement between mice in HD and DEX groups (P &gt;0.05). Both GD and HD treatment markedly attenuated lung inflammation (P &lt;0.05), and HD treatment demonstrated more significant therapeutic function in alleviating lung inflammation than that of GD and DEX treatment (P &lt;0.05). Both GD and HD treatment resulted in a significant reduction in IL-4 and IL-17A levels and an increase in the IFN-γ level in serum compared with the A group (P &lt;0.05). The effect of HD in lowering the IL-4 and IL-17A level was significantly greater than that of GD (P &lt;0.05), and was not significantly different from DEX (P &gt;0.05). HD treatment significantly reduced the serum level of IL-5 and eotaxin compared with the A group (P &lt;0.05), however, mice in the GD treatment group did not demonstrate this effect. GD and HD treatment significantly reduced IL-4 and eotaxin mRNA expression compared with the A group (P &lt;0.05). HD treatment significantly reduced IL-5 mRNA expression compared with the A group (P &lt;0.05). There was a significant difference between the GD and HD treatment groups in reducing IL-5 and eotaxin mRNA expression (P &lt;0.05). HD treatment was more effective in down-regulation of IL-5 in serum and eotaxin level both in serum and lung than DEX (P &lt;0.05). Compared with the A group, an obvious increase in mRNA expression of IFN-γ was observed in both the GD and HD treatment groups (P &lt;0.05). However, the effect of HD treatment on increase of IFN-γ mRNA expression was more apparent than GD and DEX treatment (P &lt;0.05). Conclusions Both GD and HD treatment could decrease AHR, attenuate lung inflammation, reduce IL-4, IL-5, IL-17A, and eotaxin levels and increase IFN-γ levels in asthmatic mice. HD treatment manifests more remarkable inhibitory effects on asthmatic inflammation than GD treatment, which could provide a guide for further research on the screening of the material basis of the best anti-inflammatory effect of BSYQT.

Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice.

To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100 μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100 μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100 μL saline (i.p.); mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B; mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γ in the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γ proteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P<0.05), and there was no significant difference between Group B and C (P>0.05); the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05); the concentrations of plasma IL-12 and IFN-γ, and spleen protein expression of IL-12 and IFN-γ in Group C mice were significantly higher than those of Group A (P<0.05). Histological observation showed obvious ear tissue exudation, erythema, swelling, desquamation of skin, and scabbing in Group A. Histopathology of the skin lesion also showed hyperkeratosis, focal-parakeratosis, stratum spinosum hypertrophy, mild sponge-like edema, a large number of lymphocytes along with plasma cell infiltration in dermis, angiectasis and hyperemia in Group A, while degree of ear skin lesion in Group B and D mice was significantly lighter than that of Group A. BCG polysaccharide nucleic acid can significantly reduce the serum IgE concentrations, increase the expression of IL-12, IFN-γ protein, correct the imbalance of Thl/Th2 in atopic dermatitis mice, and has obvious inhibitory effect on atopic dermatitis in NC/Nga mice.

Effect of Korean Red Ginseng on Artificial Sand Dust (ASD) Induced Allergic Lung Inflammation

Asian sand dust is known to promote various respiratory symptoms or disorders. For the prevention of harmful health effects by Asian sand dust, the best strategy is known to avoid or reduce exposure to the Asian sand dust. Several studies have shown that Korean red ginseng (RG) has anti-inflammatory and anti-allergic effects. The study aimed to clarify the effect of Korean red ginseng intake on lung inflammation responses to artificial sand dust (ASD) similar to Asian sand dust. BALB/c mice were divided into five groups (n=12) of control (saline), ovalbumin (OVA), OVA with ASD, OVA plus RG with ASD, and OVA plus dexamethasone (DEXA) with ASD. Histopathologic evaluation of lung was conducted. Interleukin (IL)-5, IL-12, interferon (IFN)-γ, IL-13, monocyte chemotactic protein (MCP)-1, and eotaxin within bronchoalveolar lavage (BAL) fluid were measured by ELISA. OVA+ASD group significantly increased concentrations of IL-5, IL-13, MCP-1, and eotaxin (P<0.01) compared to the control. OVA+ASD+RG group showed significant decreased levels of IL-2, IL-13, MCP-1 and eotaxin (P<0.01) compared with OVA+ASD. Between RG and DEXA treatment groups, there was no significant difference in all cytokines and chemokines. The inflammatory cells were significantly decreased in treatment groups with RG or DEXA compared to OVA+ASD group. This study suggests a beneficial effect of Korean RG administration in preventing inflammation of lung resulting from Asian sand dust.

Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model.

The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation.

The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan.

We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.

Effect of topical dexamethasone in reducing dysfunction after facial nerve crush injury in the rat

ObjectiveTo date, the effect of topical steroid after a crush injury to rat facial nerve has rarely been reported on. The aim of this study was to investigate the effects of topical dexamethasone on recovery after a crush injury to the rat facial nerve, by functional, electrophysiological, and morphological evaluation. Materials and methodsWe investigated the effects of topical dexamethasone on recovery after a crush injury to rat facial nerve by functional, electrophysiological and morphological evaluation. ResultsThe functional recovery using vibrissae movement was significantly high scores in the experimental group than control group at two and three weeks post-crush. The recovery of the threshold of muscle action potential was significantly lowered in the experimental group compared to the control (p<0.05). However, there was no statistical significance in the nerve conduction velocity. The dexamethasone treatment groups showed a larger axon diameter and thicker myelin sheath than the control group. ConclusionFrom our results, topical dexamethasone accelerates recovery of the crush-injured facial nerve.

Induced lactation in heifers: Effects of dexamethasone and age at induction on milk yield and composition

Milk production in heifers induced into lactation is lower than that of postpartum primiparous cows. A method to improve milk production in induced lactations may provide opportunities for increased profitability as well as increase our understanding of the mechanisms that regulate mammary gland development and colostrum composition. The present study was conducted to determine if dexamethasone administration at the onset of milking or age at lactation induction would affect milk production in heifers induced into lactation. Holstein heifers at 14 [n=20; 354±38 kg of body weight (BW)] and 18mo of age (n=20; 456±30kg of BW) were assigned randomly to dexamethasone (DEX) or control (CON) treatment groups in a 2× 2 factorial arrangement with age and dexamethasone treatment as the 2 factors. Heifers were induced into lactation with daily subcutaneous injections of estradiol-17β and progesterone (0.075 and 0.25 mg/kg of BW per d, respectively) on experimental d 1 to 7. They also received bovine somatotropin (bST) every 14d beginning on experimental d 1. Milking began on experiment d 18 (lactation d 1). Dexamethasone (10mg) was administered on lactation d 1 and 2 following the morning milking; CON heifers did not receive dexamethasone. Milk yield from d2 to 15 of lactation of heifers receiving DEX (7.8kg/d) was greater than that of CON heifers (6.0 kg/d) but was similar thereafter through 305d of lactation (18.2kg/d). Milk production to d 11 was similar for 14- and 18-mo-old heifers but was greater for 18- (18.9kg/d) than for 14-mo-old animals (17.4kg/d) through 305 d in milk. Milk fat percentage increased initially and was greater in DEX (4.51%) compared with CON (3.53%) heifers until 21d in milk. Milk protein and lactose concentrations were not affected by DEX treatment. Age at induction did not affect milk fat, protein, or lactose percentages. Mean milk IgG concentration declined from 107.4mg/mL on d 1 to 5.0mg/mL on d 7 of lactation, tended to be greater for 18- compared with 14-mo-old heifers, and was not different due to DEX treatment. Administration of DEX to heifers induced into lactation increased initial milk production during the first 2 wk of lactation but this effect did not persist through 305 DIM. Treatment with DEX appeared to stimulate mammary cell differentiation but did not change the rate of decline of milk IgG concentrations. Higher milk yield in 18-mo-old heifers may be due to greater mammary epithelium, higher body mass, or both.

Effect of secondary lymphoid tissue chemokine suppression on experimental ulcerative colitis in mice.

The secondary lymphoid tissue chemokine (CCL21) is closely associated with lymphoid homing and anti-tumor immune responses. CCL21 also has a chemotactic effect on intestinal lymphocytes. This study mainly focused on CCL21 expression in experimental ulcerative colitis and on the effects of CCL21 suppression on this disease in mice. The mouse colitis model was induced by dextran sulfate sodium (DSS) in 40 female BALB/c mice that were equally distributed into five groups: control, DSS, propylene glycol, triptolide (TL), and dexamethasone treatment groups. The disease activity index, general morphology score of the colon, and histological pathology score of colon tissues were evaluated. CCL21 expression was examined in colons of mice by immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting analysis. CCL21 was upregulated in the mouse model of ulcerative colitis (control group vs DSS group/propylene glycol group, P<0.01). The TL and dexamethasone treatments improved colitis symptoms and decreased CCL21 expression (TL group/dexamethasone group vs DSS group/propylene glycol group, P<0.05). In conclusion, CCL21 was shown to be involved in the induction of ulcerative colitis. Suppression of CCL21 expression decreased damage induced from ulcerative colitis, indicating that CCL21 targeted therapy might be an effective treatment for this disease.

Adiponectin decreases lipids deposition by p38 MAPK/ATF2 signaling pathway in muscle of broilers

Adiponectin is an adipokine hormone that influences glucose utilization, insulin sensitivity and energy homeostasis. To investigate the effect of adiponectin on lipids deposition in broilers, rosiglitazone and dexamethasone were used to treat broilers. A total of 120 twenty-three-day-old male Cobb broilers were randomly divided into 3 groups for 3weeks of drug treatment. Serum adiponectin level and fatty acid composition in muscles were measured. Adiponectin, adiponectin receptors (adipoR1, adipoR2) and lipid metabolism-related genes expression levels in muscles were measured using real-time PCR. Western blot was used to measure the expression levels of lipid metabolism-related proteins and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)/activating transcription factor 2 (ATF2) pathway marker proteins. Rosiglitazone increased serum adiponectin concentration and the expression levels of adiponectin and adipoR1 (P<0.05), while dexamethasone had the opposite effect. Intramuscular fat content, total fatty acid, saturated fatty acid and monounsaturated fatty acid reduced in the rosiglitazone treatment group (P<0.05). In the rosiglitazone treatment group, the expression levels of lipogenic genes and proteins decreased in the muscles, whereas the expression levels of lipolysis genes increased. Meanwhile, the phosphorylation levels of p38MAPK and ATF2 increased with supplementation of rosiglitazone and decreased in the dexamethasone treatment group (P<0.01). These results indicated that rosiglitazone and dexamethasone could regulate adiponectin expression in muscle of broilers and adiponectin had an anti-lipogenic effect by p38 MAPK/ATF2 signaling pathway.

Dexamethasone multifunctional role in spreading depression

Spreading depression (SD) is a neural hyperexc/INS;itabi/INS;lity, which spreads/INS; to adjoining area of brain cortical; slowly continues/INS; through the brain and changes /INS;neural electrical and metabolic activity. It has been proved that SD plays/INS; a dramatic role in some neurological disorder through the changes it causes/INS;. Previous studies applied various types of drugs through diverse pharmacological aspects to relieve /INS;SD wave distribution. However most have been abort due to their unpleasant side effects. In the present study we seek for dexamethasone's (Dex) multifunctional properties in order to protect cellular damage and/INS; then prevent even other neurological disorder accuracy following SD. Animals/INS; were /INS;randomly divided into five groups/INS; including /INS;CTRLs, sham, spreading depression and dexamethasone treatment group. Animals/INS; were anesthetized and a /INS;cannula as well as an /INS;electrode was /INS;established above the brain cortex. Intracerebral KCl was used to induce repetitive cortical SD for 4 continuous week. Following each induction memory retrieval tests/INS; (T-maze) were done. The brains were removed after 4 weeks. Histopathologically estimation was used to testify dexamethasone effect. In addition dexamethasone effects on blood brain barer (BBB) to facilitate /INS;substance recovery in cerebral fluid were tested by Evans blue. By repetitive SD memory retrieval was impaired due to increscent of dark neural seen in several regions of juvenile rat brain. Besides/INS; that brain electrical activity determination showed slake of neural activity after SD induction. Neural cell recoveries after SD due to increscent of substance passage through BBB were promoted/INS;.

Experimental treatment of pulmonary interstitial fibrosis with human umbilical cord blood mesenchymal stem cells

To investigate the therapeutic effect and possible action mechanism of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the treatment of bleomycin-induced pulmonary fibrosis in rats. The second generation of hUCB-MSCs was cultured to the fourth generation. Sixty healthy male Sprague-Dawley rats (clean grade) were randomly and equally divided into 4 groups: bleomycin group, stem cell treatment group, dexamethasone treatment group, and negative control group. A pulmonary fibrosis model was established by intratracheal instillation of bleomycin in the bleomycin group, stem cell treatment group, and dexamethasone treatment group. The stem cell treatment group was injected with stem cells labeled with 5-bromo-2-deoxyuridine (Brdu) via the caudal vein immediately after the model was established. The dexamethasone treatment group was intraperitoneally injected with dexamethasone for 7 d from the next day after the model was established. The negative control group was given an equal volume of normal saline by intra-tracheal instillation. In each group, 5 rats were sacrificed in the 7th, 14th, and 28th days. The expression of transforming growth factor β1 (TGF-β1) and Brdu-labeled stem cells were observed by HE and Masson staining and immunohistochemistry. Lung hydroxyproline content was determined by acid hydrolysis. The stem cell treatment groups had Brdu-labeled stem cells seen in lung tissue in the 7th, 14th, and 28th days. Compared with the negative control group, the bleomycin group, stem cell treatment group, and dexamethasone treatment group had significantly increased scores of alveolitis and pulmonary fibrosis (P < 0.05). In the 7th, 14th, and 28th days, the scores of alveolitis in stem cell treatment group and dexamethasone treatment group were significantly lower than those in bleomycin group (P < 0.05); in the 28th day, the scores of pulmonary fibrosis in stem cell treatment group and dexamethasone treatment group were significantly lower than that in bleomycin group (P < 0.05). There were no significant differences in scores of alveolitis and pulmonary fibrosis between the dexamethasone treatment group and stem cell treatment group (P > 0.05). Compared with the bleomycin group, the stem cell treatment group and dexamethasone treatment group had significantly decreased number of TGF-β1-positive cells and hydroxyproline content in lung tissue at all time points (P < 0.05). There were no significant differences in number of TGF-β1-positive cells and hydroxyproline content in lung tissue between the stem cell treatment group and dexamethasone treatment group (P > 0.05). hUCB-MSCs can be transplanted into damaged lung tissue and effectively reduce alveolitis and pulmonary fibrosis in the early stage of pulmonary fibrosis. The action mechanism of hUCB-MSCs may involve inhibiting the expression of TGF-β1 and reducing the formation of collagen.

Changes of regulatory T cells distribution in trinitrobenzene sulfonic acid induced mice colitis

Objective To investigate the changes of regulatory T cells (Treg) distribution in trinitrobenzene sulfonic acid (TNBS) induced mice colitis and the therapeutic effects of dexamethasone (DEX).Methods A total of 40 mice were evenly divided into healthy control group,ethanol control group,model group and DEX treatment group.The model group was given 2.5 mg TNBS through enema,while healthy control group and ethanol control group were administered with 0.9％ NaCl solution and ethanol solution respectively.DEX treatment group was intraperitoneal injected with DEX (0.6 mg/kg) since the first day after modeling.Mice were executed at 3rd,5th and 7th day after modeling,mice body weight of each group were observed and the rate of both CD25+ forkhead box P3(Foxp3) positive and CD4 positive cells in spleen and mesenteric lymph nodes were measured by flowcytometry.At the 7th day,disease activity index (DAI) and colonic histopathological score were evaluated,the expression of Foxp3 in colon tissue were measured by immunohistochemistry.t-test was applied for each group comparison.Results Compared with healthy control group and ethanol control group,the mice body weight of model group significantly decreased (t=3.604 and 2.422,both P＜0.05); DAI score and colonic histopathologic score increased (t=2.630 and 2.438,both P＜0.05;t=7.910 and 6.600; both P＜0.01).Compared with the model group,DAI score decreased (t=2.076,P＞0.05) and histopathologic severity in DEX treatment group improved significantly (t =2.320,P＜0.05).At the 7th day after modeling,the rate of both CD25+ Foxp3 positive and CD4 positive cells in spleen and mesenteric lymph nodes of model group was 3.320％ ± 0.533％ and 2.888％±0.379％,lower than that of healthy control group (5.379％ ±0.518％ and 4.688％±0.553％; t=2.769 and 2.686; both P＜0.05).After DEX treatment,the rate increased.The expression of Foxp3 in colon tissue of healthy control group,model group and DEX treatment group was 3.000±0.577,7.200±0.800 and 6.000±0.931 per high power field respectively,and the expression of model group and DEX group significantly increased (t=4.257 and 2.739,both P＜ 0.05).Conclusions The distribution of Treg in spleen and colon were abnormal in TNBS-induced mice colitis model.DEX may improve the disease state of the mice model through upregulating Treg. Key words: Colitis; Disease models, animal; CD4-positive T-lymphocytes; Dexamethasone

Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation

The aim of this study was to investigate the neuroprotective effect of magnesium sulfate and dexamethasone on oxidative damage in intrauterine ischemia. In this study, 19-day pregnant rats were divided into five groups. Fetal brain ischemia was achieved in the ischemia/ reperfusion (I/R) group by bilaterally closing the utero-ovarian artery with aneurysm clips for 30 min and subsequently removing the aneurysm clips for 60 min for reperfusion. Mg (600 mg/kg) and dexamethasone (0.25 mg/kg) were administered 20 min before the I/R insult. The lipid peroxidation in the brain tissue was determined by the concentration of thiobarbituric acid reactive substances (TBARS). The mitochondrial score was calculated after an evaluation with electron microscopy. Both the electron microscope and TBARS data showed a significant difference between the control and I/R groups. The Mg and dexamethasone treatment groups exhibited significantly lower TBARS values compared to the IR group. Similarly, the mitochondrial scores in the Mg and dexamethasone treatment groups were significantly lower than those in the I/R group. Result showed that magnesium sulfate and dexamethasone prevent lipid peroxidation and reduce mitochondrial injury thus suggests neuroprotective effects in fetal rat brain in intrauterine ischemia-reperfusion (I/R) injury.