Dexamethasone ; therapeutic use ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; drug therapy ; physiopathology ; Methylprednisolone ; therapeutic use ; Prednisolone ; therapeutic use

Arthritis, Juvenile ; drug therapy ; Glucocorticoids ; adverse effects ; pharmacology ; therapeutic use ; Humans

OBJECTIVE: To evaluate the benefits and toxicities of different corticosteroid regimes in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: MEDLINE (Jan. 1963-Mar. 2007), elsevier (Jan. 1997-Aug. 2006), OVID databank (Jan. 1993-Aug. 2006), Springer databank (Jan. 1994-March 2007), the Cochrane Controlled Trials Register (Cochrane Library, Issue Feb. 2006), Cochrane Renal Group Specialised Register (Jul. 2006), EMBASE (Jan. 1980-Mar. 2007) and CNKI (Jan. 1994-Mar. 2007) etc, were searched by the terms primary nephrotic syndrome, glucocorticoid, corticosteroid, steroid, prednisone, methylprednisolone, dexamethasone and children etc for the human clinical trials about glucocorticoid (GC) administration in primary nephrotic syndrome (PNS) (aged 3 months to 18 years), controlled or semi-controlled ones, including unpublished documents from scientific meetings and theses, and similar documents listed in the references of the above documents were also included. All the studies were evaluated strictly according to Jadad Standard, and the Meta-analysis were adopted. Review manager 4.2 software was used to analyze the data. The odds ratio was calculated for the relapse rate and side effect from the initial episode to the end of follow-up between the patients treated with corticosteroids and the controls. RESULTS: Totally 12 trials with 868 subjects meeting the criteria were included in this review. A Meta-analysis of 7 trials, which compared between 2 months of prednisone and 3 months or more in the first episode, showed that longer treatment duration significantly reduced the risk of relapse at 12-24 months (RR=0.70,95% CI:0.60-0.89),without an increase of side effect. There was a negative linear relationship between the duration of treatment and risk of relapse (r2 =0.66, P=0.05). CONCLUSION (1) Children in their first episode of SSNS should be treated for at least 3 months of GC. The therapeutic effect of patients in the primary nephrotic syndrome treated with GC for 12 weeks was prior to that for 8 weeks, compared with that in the controls. It could reduce the relapse rate of half year, the longer treatment duration in the NS patients at the first relapse was, the lower relapse risk was.(2) Compared with alternative GC administration, standard GC administration can reduce the side effects; Course more than 1 year of GC administration can reduce the 2-year relapse rate. Hence in children who relapse frequently, multicentre, well-designed experiments should be adopted.
Child ; Drug Resistance ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Nephrotic Syndrome ; drug therapy

Glucocorticoids (GCs) are the most effective group of medications available to treat inflammation. Although most patients with inflammation respond to GC, a small group of patients exhibit persistent GC-resistance with prolonged inflammation. Previously, it was proposed that the GC-resistance is caused by low amount of human GC receptor (hGR alpha) and/or excessive presence of a GC receptor isoform, hGR beta that was generated from alternative splicing of the hGR message. We have tested this hypothesis by investigating correlation between the expression pattern of hGR mRNAs in patients with inflammatory nasal polyps and the effectiveness of GC treatment.? We have performed reverse transcription PCR analysis of mRNAs coding each hGR alpha and hGR beta in nasal tissues.? hGR alpha mRNA was more expressed in patients with nasal polyps than in normal subjects. However, the elevated hGR alpha mRNA expression was decreased after GC treatment. Compared with hGR alpha mRNA expression, level of hGR beta mRNA expression was very low in all groups. In patients, hGR beta mRNA was expressed at a similar level regardless of GC efficacy, indicating that there is no correlation between the GC sensitivity and the expression level of hGR beta mRNA. Thus, persistent GC-resistance is not associated with low expression of hGRa or over- expression of hGR beta.
Treatment Failure ; Reverse Transcriptase Polymerase Chain Reaction ; Receptors, Glucocorticoid/*metabolism ; RNA, Messenger/metabolism ; Nasal Polyps/drug therapy/*metabolism/surgery ; Middle Aged ; Male ; Humans ; Glucocorticoids/*pharmacology/therapeutic use ; Gene Expression ; Female ; *Drug Resistance ; Child ; Aged ; Adult ; Adolescent

OBJECTIVETo establish rat models of Steroid-avascular necrosis of femoral head, observe the effects of activating blood circulation of chinese herbal medicine on genetic expression of transforming growth factor-beta1 (TGF-beta1). To interpret the mechanism of the effect on Steroid-avascular necrosis of femoral head by activating blood circulation,and offer a effective method to clinical.

METHODSCleaner-40 SD rats,half males and half females, weight (200 +/- 20) g, were randomly divided into 2 groups: 4 rats were in common group and 36 rats were in medel group. The rats in medel group were administered with 24.5 mg/kg hydroxyprednisone twice a week peritoneal injection for 6 weeks induced to femur head necrosis. The rats in common group were through gluteus injection as control. There were 4 rats were killed in each group after 6 weeks, to be assure that the model were succed. All surplus rats were divided into treatment group and control group:the treatment group were administrated with activating blood circulation of Chinese herbal medicine 12.3 ml/kg per day,the control group were administrated with sodium chloride 12.3 ml/kg per day. Then, after 6 and 8 weeks, killed the animal and detected all indexes.

RESULTS(1) The expression of TGF-beta by immunohistochemistry and image analysis: the expression of femoral head TGF-beta increased significantly in treatment group than in control group and two group had significant differences. (2) Serum levels of TGF-beta1: in the treatment group serum expression of TGF-beta1 increased,compared with the control group had significant difference (P < 0.01). (3) The femoral head local TGF-beta1 mRNA transcription: treatment group in the first six weeks, expressed that the increase in the first eight weeks, expressed also reduced,and the control group in the first six weeks, expressed a decrease in the first eight weeks,was not detected to TGF-beta1 mRNA expression of difference between the two groups was significant (P < 0.01). TGF-beta1 mRNA in serum and the femoral head with local expression of TGF-beta1, in consistency.

CONCLUSIONRat abdominal cavity prednisolone acetate injection plus intermittent standing avascular necrosis modeling stability, good repeatability. Taohongsiwu through the promotion of hormone-ischemic necrosis of the femoral head rat model of TGF-beta1 mRNA transcription, and promote expression of TGF-beta1.

Animals ; Blood Circulation ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Femur Head Necrosis ; chemically induced ; drug therapy ; Glucocorticoids ; pharmacology ; Male ; Medicine, Chinese Traditional ; Rats ; Transforming Growth Factor beta1 ; blood ; genetics ; physiology

This study was aimed to investigate the sensitive index for predicting the sensitivity of patients with multiple myeloma (MM) to glucocorticoid (GC). MM1.S, MM1.R cell lines and 10 MM patients sensitive or non-sensitive to GC were enrolled in this study. The expression of heat shock protein 90 (HSP90) and P23 in peripheral blood mononuclear cells (PBMNC) of MM patients was detected by Western blot, and its relation with GC resistance was explored. The results showed that there were no differences in HSP90, GR and IκB-α expressions among MM1.S, MM1.R, PBMNC of normal persons and MM patients, while there was apparent difference in P23; along with increasing of dexamethasone dose, the survival rate of MM1.S decreased, but that of MM1.R did not change so obviously. Among 7 cases with P23 low expression, combination treatment scheme with GC was effective in 6 cases (86%), uneffective in 1 cases (14%); while among 3 cases with P23 high expression, 1 cases (33%) showed effective to combination treatment with GC, 2 cases (67%) showed uneffective (P < 0.05). It is concluded that the P23 expression may predict the sensitivity of MM patients to GC and may be used as index for guiding clinical treatment.
Aged ; Aged, 80 and over ; Female ; Glucocorticoids ; pharmacology ; therapeutic use ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Male ; Middle Aged ; Molecular Chaperones ; metabolism ; Multiple Myeloma ; diagnosis ; drug therapy ; metabolism ; Phosphoproteins ; metabolism ; Tumor Cells, Cultured

OBJECTIVE: To study the effect of intranasal glucosteroid on the expression of PKC, Bcl-2 and Bax in nasal polyps. METHOD: The expression of PKC, Bcl-2 protein and Bax were detected with immunohistochemistry in nasal polyps from the patients (n=16) pre and post treated for 4 weeks with intranasal glucosteroid. And which compared with normal mucous membrane of inferior turbinate concha. RESULT: The PKC and Bcl-2 protein expressed significantly higher in the pretreated patients (P < 0.01), which were significant reduced in the post treated patients compared with pretreated ones. The expression of Bax protein significantly higher in the post treated patients (P < 0.05). CONCLUSION Our findings indicated that abnormal expression of apoptosis related genes in nasal polyps tissues might play an important role in the occurrence and progression of nasal polyps. The treatment of intranasal glucosteroid may regulate the expression of apoptosis related genes.
Administration, Intranasal ; Adolescent ; Adult ; Aged ; Female ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Male ; Middle Aged ; Nasal Polyps ; drug therapy ; metabolism ; Protein Kinase C ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Young Adult ; bcl-2-Associated X Protein ; metabolism

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

OBJECTIVEMany studies have shown that glucocorticoids play a crucial role in the development of obesity and insulin resistance. This study investigated the therapeutic effects of long-term inhibition of glucocorticoid activity on obesity and insulin resistance.

METHODSFour-week-old male Sprague-Dawley (SD) rats were randomly fed with a high-fat diet (fat content accounting for 20% of total calorie) (control group, n=8) or with a high-fat diet along with glycyrrhetic acid (GE, 800 mg/L), an inhibitor of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) for 24 weeks (GE-treated group, n=9). The body weights and the amount of food intake were monitored weekly and daily, respectively. After 24 weeks of GE treatment, oral glucose tolerance tests were performed. Blood glucose was measured by glucose oxidase method. The levels of plasma glucocorticoids, insulin and leptin were measured with radioimmunoassay. The levels of serum cholesterol and triglyceride were determined with an automatic measuring analyzer.

RESULTSThe food intake amount decreased significantly in the GE-treated group from 6 weeks and body weight gain was markedly less from 8 weeks after GE administration compared with the control group. After 24 weeks of treatment, the plasma levels of leptin and insulin in GE-treated rats were significantly reduced compared with the control group. The serum levels of cholesterol and triglyceride decreased markedly compared with the control group and the levels of blood glucose were significantly lower 15, 30, 60 and 120 minutes after oral glucose load in the GE-treated group compared with the control group.

CONCLUSIONSLong-term GE treatment may contribute to resisting diet-induced obesity and insulin resistance.

11-beta-Hydroxysteroid Dehydrogenases ; antagonists & inhibitors ; Animals ; Body Weight ; drug effects ; Dietary Fats ; administration & dosage ; Enzyme Inhibitors ; pharmacology ; Glucocorticoids ; physiology ; Glucose Tolerance Test ; Glycyrrhetinic Acid ; pharmacology ; therapeutic use ; Insulin ; blood ; Insulin Resistance ; Leptin ; blood ; Male ; Obesity ; drug therapy ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. METHODS: COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-β) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. RESULTS: Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ± 6.1 vs. 20.1 ± 3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ± 1.2 vs. 6.7 ± 0.5 pg/mL, P = 0.01; lung TGF-β: 122.4 ± 20.8 vs. 81.9 ± 10.8 pg/mL, P < 0.01; serum TGF-β: 38.9 ± 8.5 vs. 20.6 ± 2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ± 0.1 fold of control vs. 0.2 ± 0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ± 0.4 μmol/μg vs. 17.4 ± 1.1 μmol/μg, P < 0.01; activity: 1.1 ± 0.1 unit vs. 1.4 ± 0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ± 0.4 μmol/μg vs. 14.1 ± 0.9 μmol/μg, P < 0.01; activity: 1.3 ± 0.1 unit vs. 1.0 ± 0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ± 0.0 fold of control vs. 0.3 ± 0.1 fold of control, P < 0.01). CONCLUSIONS This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway.
Animals ; Antimicrobial Cationic Peptides ; pharmacology ; therapeutic use ; Glucocorticoids ; metabolism ; Histone Deacetylase 2 ; metabolism ; Humans ; Inflammation ; chemically induced ; drug therapy ; Lipopolysaccharides ; pharmacology ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism ; Rats ; Rats, Wistar ; Smoking ; adverse effects ; Tumor Necrosis Factor-alpha ; metabolism