This study was aimed to investigate the effects of different mobilization methods on mobilization and collection of peripheral blood stem cells in healthy donors and the adverse effect of collection, as well as hematopoietic construction in recipients. A total of 43 donors between January 2008 and May 2013 were divided into the simple mobilization group and the combined mobilization group. The simple group was subcutaneously injected with 5.0-10.0 µg/(kg·d) recombinant human granulocyte colony-stimulating factor (rhG-CSF), and the combined mobilization group was treated with rhG-CSF and intravenously dripped with 10 mg dexamethasone for 2-4 hours before collection. The acquisition and count of MNC and CD34(+) cells in different groups, the relationship between the stem cells and MNC count in blood before collection, and the adverse reactions were analyzed; the hematopoietic reconstruction of recipients was investigated. The results showed that the hematopoietic stem cell number of the two groups meet the demands. The count of MNC and CD34(+) cells in the simple mobilization group was more than that in the combined mobilization group. The MNC count in two groups positively correlated with peripheral blood MNC count before collection. The decline of hemoglobin and platelet levels was more obvious in the simple mobilization group than that in combined mobilization group. The adverse reactions of collection in the simple mobilization group could be well tolerated and reversed. There was no adverse reaction in the combined mobilization group. The differences of conditioning regimens between two groups were not statistically significant and the hematopoietic reconstruction time of combined group was shorter than that in the simple mobilization group.It is concluded that the adverse reactions in process of collection can be reduced, and enough hematopoietic stem cells can be collected by G-CSF plus dexamethasone in mobilization of peripheral blood stem cells. The count of MNC in peripheral blood before collection can be still used as a reference index to evaluate the acquisition of MNC. Especially the combination with dexamethasone for stem cell mobilization can promote the hematopoietic reconstruction of the recipients.
Adolescent ; Adult ; Child ; Child, Preschool ; Dexamethasone ; pharmacology ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cells ; drug effects ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Recovery of Function ; Young Adult

INTRODUCTIONGlucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11β-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11β-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.

METHODSA total of 30 male Sprague-Dawley rats (aged three months, weighing 200-250 g) were divided into three groups of ten each. Group 1 rats were the baseline control, which were sacrificed untreated at the beginning of the study. Group 2 rats underwent sham operation and were administered with vehicle olive oil intramuscularly at 0.05 ml/kg. Group 3 rats were adrenalectomised and administered with an intramuscular injection of dexamethasone 120 μg/kg body weight/day. The treatment was started two weeks after the operation, for a duration of two months. Plasma osteocalcin, plasma pyrodinoline, plasma corticosterone and 11β-HSD1 were measured, and bone histomorphometry analysis was performed.

RESULTSDexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11β-HSD1 dehydrogenase activity of the bone, along with a higher plasma level of the bone resorption marker, pyridinoline. Dexamethasone treatment also caused a reduction in trabecular volume, number and thickness, and an increase in trabecular separation.

CONCLUSIONLong-term glucocorticoid treatment reduces the 11β-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenase Type 1 ; metabolism ; Adrenal Cortex Hormones ; metabolism ; Amino Acids ; pharmacology ; Animals ; Body Weight ; Bone and Bones ; metabolism ; Corticosterone ; blood ; Dexamethasone ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; methods ; Gene Expression Regulation, Enzymologic ; Glucocorticoids ; metabolism ; Humans ; Male ; Osteoporosis ; metabolism ; Rats ; Rats, Sprague-Dawley

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; blood ; immunology ; prevention & control ; Concanavalin A ; adverse effects ; Cytokines ; blood ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Female ; Hepatocytes ; drug effects ; pathology ; Liver ; drug effects ; immunology ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Peroxidase ; blood ; Protective Agents ; pharmacology ; Random Allocation ; Saponins ; pharmacology ; Triterpenes ; pharmacology

OBJECTIVEThe pathogenesis of mesangial proliferative glomerulonephritis (MsPGN) and mechanisms of glucocorticoid (GC) resistance have not been fully identified. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte activation. The objective of the study is to investigate the CTLA-4 expression and apoptosis in lymphocytes of children with MsPGN and the effects of dexamethasone (Dex) on the CTLA-4 expression and apoptosis.

METHODSBlood samples were collected from 36 children with MsPGN and 30 healthy children. CTLA-4 expression in in vitro cultured lymphocytes with or without Dex treatment was measured by flow cytometry following direct immune fluorescene. The rate of apoptosis in the lymphocytes was evaluated by annexin V-FITC and propidium iodide staining.

RESULTSThe CTLA-4 expression and apoptosis in lymphocytes from children with MsPGN were significantly lower than those in the healthy control children in the absence or presence of Dex treatment (p<0.05). There was a positive correlation between CTLA-4 expression and apoptosis in lymphocytes (p<0.05).

CONCLUSIONSAbnormal CTLA-4 expression may participate in the pathogenesis of MsPGN and be one of mechanisms of GC resistance.

Antigens, CD ; blood ; Apoptosis ; drug effects ; CTLA-4 Antigen ; Child ; Dexamethasone ; pharmacology ; Female ; Glomerulonephritis, Membranoproliferative ; drug therapy ; etiology ; Humans ; Lymphocytes ; drug effects ; immunology ; Male

OBJECTIVETo investigate the effect of nebulized total ginkgo flavone glycosides (TFG) on Th1/Th2 imbalance in mice with athma.

METHODForty-eight BALB/C mice were randomly divided into four groups: group A (control group, n=12); group B (asthmatic model group, n=12); group C (TFG nebulized treated group, n=12); group D (dexamethasone intraperitoneal treated group, n=12). The asthmatic model was established by sensitivity and local activation with Ovalbumin(OVA) and aluminum hydroxide Al(OH)3. TFG (50 g x L(-1), per aerosol per six mice, 30 minutes) was nebulized 20 days after modeling, while dexamethasone (1 g x L(-1)) was intraperitoneal once daily for 10 days. Perfusate of bronchoalveolar lavage fluid(BALF) was collected on day 32. The level of IL-4, IFN-gamma in BALF, and the level of total IgE in serum was determined. The airway inflammation pathology change and the expression of GATA-3 protein in lungs was detected by immunohistochemical staining.

RESULTCompared with model group, the decreased content of IL-4(49.30 +/- 7.95) ng x L(-1) and increased level of IFN-gamma (49.08 x 5.46) ng x L(-1). were found in BALF, and the level of total IgE (9.47 +/- 1.52) microg x L(-1) in serum also decreased in TFG treated group. In model group, smooth muscle hypertrophing, mucous hyperemia, mucous layer thickening, and inflammatory cell in filtration were observed. Phlegmasia was appeared in the bronchi, which was filled with lots of mucus. In contrast, the inflammatory reaction in TFG and Dexamethasone treated group was less obvious. Expression of GATA-3 was markly increased in model group with decreased expression in TFG treated group.

CONCLUSIONNebulized TFG showed a therapeutic effect for asthmatic mice, the mechanism may be explained by blockingnnnn GATA-3 expression and regulating the disorder Th1/Th2 imbalance.

Aluminum Hydroxide ; pharmacology ; Animals ; Asthma ; chemically induced ; drug therapy ; metabolism ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Dexamethasone ; therapeutic use ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Female ; Flavones ; Flavonoids ; chemistry ; GATA3 Transcription Factor ; metabolism ; Ginkgo biloba ; chemistry ; Glycosides ; chemistry ; therapeutic use ; Immunoglobulin E ; blood ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lung ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; pharmacology ; Random Allocation ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism

OBJECTIVE: The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. MATERIALS AND METHODS: An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. RESULTS: Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). CONCLUSION: Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.
Animals ; Blood-Aqueous Barrier/*drug effects ; Blood-Retinal Barrier/*drug effects ; Capillary Permeability/drug effects ; Cats ; Contrast Media ; Dexamethasone/*pharmacology ; Emulsions ; Glucocorticoids/*pharmacology ; Image Enhancement ; Magnetic Resonance Imaging/*methods ; Triolein/*adverse effects

OBJECTIVETo study the effect of dexamethasone on spontaneously apoptosis, bcl-2, and neuclear facor kappa (NFkappaB) expressions of polymorphonuclear neutrophil (PMN) from postburn rabbits.

METHODSPMN were isolated from 8 rabbits on 24 postburn hours and cultured with normal serum (NS), burn serum (BS), normal serum plus dexamethasone (ND), and burn serum plus dexamethasone (BD) for 24 hours, respectively. The quantification of apoptosis was analyzed by acridine orange + ethidium bromide fluorescent staining and flow cytometry , and the contents of bcl-2 and NFkappaB protein detected by immunohistochemical method.

RESULTSIn the BS group, the percentage of apoptotic PMN decreased (compared with NS group, 6.18 +/- 0.96 vs. 21.77 +/- 2.32, P<0.05), and the contents of bcl-2 and NFkappaB protein increased (compared with NS group, 83.27 +/- 5.45 vs. 49.95 +/- 2.67, P<0.05). When compared with BS group, the apoptotic percentage of BD group increased (12.67 +/- 0.71 vs. 6.18 +/- 0.96, P<0.05), and the content of NFkappaB protein reduced (0. 1031 +/- 0.0154 vs. 0.1802 +/- 0.0130, P<0.05), but no significant difference between ND and NS group was found.

CONCLUSIONDexamethasone decreases the inhibition of PMN apoptosis by bumn serum, which may be associated with the down-regulation of NFKB expression.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Apoptosis ; drug effects ; Burns ; blood ; Dexamethasone ; pharmacology ; NF-kappa B ; biosynthesis ; blood ; Neutrophils ; drug effects ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; blood ; Rabbits

OBJECTIVEThe metabolic character of tetramethylpyrazine (TMPz) in rat liver microsomes was studied in vitro and in vivo to identify which isoforms of cytochrome P450 were responsible for TMPz metabolism in rats, offer the theoretical foundation for the fact that it is rational to use medicine in clinic.

METHODSet up UV- HPLC method of TMPz, determine concentration of TMPz and its formation in rat plasma and liver microsomes incubation solution, analyze the correlation between TMPz's metabolic eliminate rate and each inducer. Erythromycin( ERY) N-demethylase activity of each sample in rat liver microsomes was measured using N-demethylation reaction of ERY as probe. The correlation between the rate of TMPz metabolite formation and the demethylase activity was analysed. After the SD rats who had been treated with inducer, inhibitor, or untreated, received administration of TMPz in vein, the plasma concentration of TMPz were determined by HPLC. Pharmacokinetic parameters of TMPz were computed and compared.

RESULTThe disppearing rate of TMPz in the incubation solutions of the rats liver microsomes, which treated with DEX, were markedly quicker than that of control group (P < 0. 01) , while no obvious difference between P-NF group or PB and control group was observed (P > 0. 05). The activity of ERY-N-demethylase in DEX-induced group was corespondingly enhanced, was much higer than that in control group. The correlation between the rate of TMPz metabolic product formation and the activity of N-demethylase was significant. After using Ket, the CYP3A inhibitor, the metabolism of TMPz could be significantly inhibited the metabolism of TMPz in rat liver microsomes. In vivo, CL( s) were larger than that of the control group,t,/2 were smaller than the control group in DEX group; By contrary, CL(s) was smaller than the control group,t1/2 was larger than the control group in Ket group.

CONCLUSIONResults suggest that CYP3A plays a major role in TMPz metabolism in rats, TMPz lie in the possibility of Interaction among the medicines between TMPz and CYP3A inducers or inhibitors when they are used in clinic.

Animals ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Dexamethasone ; pharmacology ; Ketoconazole ; pharmacology ; Male ; Metabolic Clearance Rate ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Pyrazines ; blood ; metabolism ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Wistar ; Vasodilator Agents ; blood ; metabolism ; pharmacokinetics

OBJECTIVETo observe the protective effect of ginsenosides (GS) or low dose of glucocorticoid dexamethasone (Dex) alone or combined in managing the liver injury and renal function after transcatheter arterial chemoembolization (TACE).

METHODS120 patients with primary liver carcinoma were randomly divided into four groups (A, B, C, D) with 30 patients in each. Group A was treated with placebo; group B with Dex; group C with GS and group D with Dex plus GS. The changes in liver and renal function after TACE were observe according to the WHO criteria for side effects of anti-cancer drug.

RESULTSCompared with group A, Dex combined with GS was able to reduce the level of TB, ALT/AST, BUN and Child-grade, which significantly protected the liver and kidney (P < 0. 05). However, Dex or GS alone could also improve some parameters of liver and renal function after TACE (P < 0.05).

CONCLUSIONDex combined with GS is effective in managing the liver injury and renal function after transcatheter arterial

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Blood Urea Nitrogen ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Creatinine ; blood ; Dexamethasone ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Ginsenosides ; pharmacology ; therapeutic use ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Iodized Oil ; administration & dosage ; Kidney ; drug effects ; pathology ; physiopathology ; Liver Diseases ; etiology ; pathology ; prevention & control ; Liver Neoplasms ; blood ; therapy ; Male ; Middle Aged ; Prospective Studies ; Topotecan ; administration & dosage

OBJECTIVEEosinophilic airway inflammation is one of the basic characteristics of allergic asthma. Toll-like receptor is one of the most important innate immunity pattern recognition receptors. Glucocorticoids (GCS) are still the most effective treatment for asthma. However, few reports of studies on regulatory mechanism of GCS on the innate immunity system are available. The mechanism of effects of GCS on TLR4 is unclear. The present study aimed at understanding the effect of dexamethasone (DXM) on change of TLR4 and mechanism of regulatory effect of TLR4 on eosinophil (EOS) apoptosis.

METHODSTwenty-seven Sprague-Dawley (SD) rats (age 28 to 42 days, body weight 120 to 180 gram) were randomly divided into the control group, asthma group and DXM group with 9 in each. Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1 mg) and Al (OH)(3), 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15, once a day for three days and continued for 30 minutes at every time. During the sensitization stage, 100 microg/ml DXM were prepared with DXM group for every other day, and the same doses DXM were prepared for every day on the stage of challenge. The histopathological changes of lung tissues were observed with light microscope (LM). EOS and other inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of OVA-sIgE in serum were measured by using "sandwich" ELISA; The expressions of TLR4 mRNA were determined by in situ hybridization, the apoptosis of EOS was detected by TUNEL.

RESULTS(1) LM showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased, airway epithelium damage and desquamation, and airway mucous plugs in asthma group, whereas DXM group showed significantly milder changes. (2) Inflammationary cells count in BALF of asthma group was significantly higher as compared to control group (P < 0.01); compared with asthma group, the total cell count, EOS absolute count and EOS% were all significantly decreased in DXM group [(2.14 +/- 0.10) x 10(9)/L, (4.78 +/- 1.23) x 10(7)/L, (2.17 +/- 0.25)%]. (3) Levels of OVA-sIgE in serum of asthma group [(83.40 +/- 6.80) microg/ml] were significantly higher than those of the control group [(14.38 +/- 4.25) microg/ml] (P < 0.01), while those of DXM group [(45.02 +/- 7.47) microg/ml] were significantly lower than asthma group (P < 0.0 1). (4) There were no significant differences in TLR4 mRNA detected by in situ hybridization between control group (24.71 +/- 0.85) and asthma group (25.81 +/- 3.56) (P > 0.05); but it significantly increased in DXM group (29.86 +/- 3.92) as compared to asthma group. (5) The percentages of apoptotic EOS in asthma group [(7.39 +/- 1.93)%] were significantly lower than those in control group [(9.06 +/- 1.52)%] (P < 0.01); and significantly higher in DXM group [(13.33 +/- 1.09)%] than in asthma group (P < 0.01). There were significantly positive correlations between TLR4 mRNA and the percentage of apoptotic EOS (r = 0.612, P < 0.01).

CONCLUSIONDXM can decrease OVA-sIgE level, induce EOS apoptosis, which may correlate with the activation of TLR4 signal transduction.

Animals ; Apoptosis ; Asthma ; chemically induced ; immunology ; Bronchoalveolar Lavage Fluid ; cytology ; Dexamethasone ; pharmacology ; Eosinophils ; immunology ; Glucocorticoids ; pharmacology ; Immunoglobulin E ; blood ; Lung ; pathology ; Ovalbumin ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; immunology ; metabolism