OBJECTIVETo identify the changes in serum insulin like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF-I and IGFBPs.

METHODSWe measured serum IGF-I and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n = 12), a remission stage group (RE, n = 12), an active stage group with glucocorticoid treatment (GNS, n = 12), and a normal control group (NC, n = 10).

RESULTS1) Compared to NC, serum levels of IGF-I and IGFBP-3 were decreased (P < 0.01); serum levels of IGFBP-1 and IGFBP-2 were increased (P < 0.01) in the ANS group. 2) Serum levels of IGF-I and IGFBP-3 were higher and IGFBP-1 and IGFBP-2 were lower in the RE Group than in theANS Group (P < 0.01). 3) Compared to the ANS group, serum levels of IGF-I and IGFBP-3 were increased (P < 0.01) and serum levels of IGFBP-1 and IGFBP-2 were decreased (P < 0.01) in the GNS group. 4) A correlation was found between serum levels of IGFBP-3 and albumin in the active stage group (r = 0.76, P < 0.01). There was also a correlation between serum levels of IGF-I and IGFBP-3 and an inverse correlation between the serum level of IGF-I and serum levels of IGFBP-1 and IGFBP-2 in the ANS group. No other correlations were observed.

CONCLUSIONSThe serum levels of IGF-I and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage. GC treatment may influence serum IGF-I and IGFBPs in children with NS. Changes in IGF-I and IGFBPs levels may play a role in the growth retardation of NS children.

Child ; Dexamethasone ; pharmacology ; Female ; Glucocorticoids ; pharmacology ; Humans ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Nephrotic Syndrome ; blood

OBJECTIVETo study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro.

METHODSUsing Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test.

RESULTSBoth LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade.

CONCLUSIONSBoth LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.

Dexamethasone ; pharmacology ; Dose-Response Relationship, Drug ; Hemoglobinuria, Paroxysmal ; blood ; drug therapy ; Hemolysis ; drug effects ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Partial Thromboplastin Time

OBJECTIVETo study the modulation of neutrophil apoptosis and necrosis, elucidate the protecton mechanisms of dexamethasone.

METHODS50 rats were divided into 5 groups. I: normal island flap. II: artery occlusion for 8 hours, saline given into peritoneal. III: venous occlusion for 8 hours, saline given into peritoneal. IV: artery occlusion for 8 hours, dexamethasone injected through peritoneal. V: venous occlusion for 8 hours, dexamethasone injected through peritoneal. Flap survived areas were measured, neutrophil apoptosis and necrosis values were ananlyzed with FCM. Their morphology were observed with light microscopy. The swallows of apoptotic neutrophil by mascrophages were studied with transmission electron microscopy.

RESULTSFlap survived areas I, IV and V groups were higher than that in II and III groups, which in I, IV, V had no significant values. Apoptotic neutrophils values in II and III groups on 1, 3 days were less than that in, but on 6 days, higher than that in I, IV and V. Necrotic neutrophils showed another tendency postoperatively when compared with its apoptotic values. There were more swallows of apoptotic neutrophils in flaps of IV, V groups than that in II, III flaps.

CONCLUSIONDexamethasone's flap protection results from modulating of neutrophils apoptosis, decreasing it's necrosis, increasing swallowings values of apoptotic neutrophils by macrophages.

Animals ; Apoptosis ; physiology ; Dexamethasone ; pharmacology ; Glucocorticoids ; pharmacology ; Ischemia ; complications ; Neutrophils ; drug effects ; physiology ; Rats ; Reperfusion Injury ; prevention & control ; Surgical Flaps ; blood supply

AIMTo build a easy and reliable rat model of insulin resistance.

METHODSChanges concerning sugar metabolism were observed in experimental rats injected intraperitoneally by different doses of dexamethasone.

RESULTSThe changes by dexamethasone in fasting blood insulin and insulin resistance prior to that of fasting blood glucose were dose and time dependent.

CONCLUSIONIt was convenience to set up a insulin resistance model induced by dexamethasone in rats which would favor other related research.

Animals ; Blood Glucose ; analysis ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

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 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

The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood. In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes. The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal). Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes. The level of leptin protein in cultured media of adipocytes treated with insulin or dexamethasone was higher than that of the control group but growth hormone or epinephrine treatment had no effect on them. Insulin administration (0.6 units/mouse) enhanced leptin mRNA as well as leptin protein in mouse adipose tissue but growth hormone administration (0.3 or 0.6 units/mouse) had no effect on them. Leptin protein level in sera of mice injected with insulin or growth hormone was not significantly different from that of control group. These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.
Adipocytes/*metabolism ; Animal ; Cells, Cultured ; Culture Media/analysis ; Dexamethasone/pharmacology ; Dose-Response Relationship, Drug ; Epinephrine/pharmacology ; Gene Expression Regulation/*drug effects ; Growth Hormone/blood/*pharmacology ; Hypoglycemic Agents/blood/*pharmacology ; Insulin/blood/*pharmacology ; Leptin/blood/genetics/*metabolism ; Male ; Mice ; Mice, Inbred ICR ; RNA, Messenger/analysis ; Transcription, Genetic/drug effects

The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood. In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes. The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal). Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes. The level of leptin protein in cultured media of adipocytes treated with insulin or dexamethasone was higher than that of the control group but growth hormone or epinephrine treatment had no effect on them. Insulin administration (0.6 units/mouse) enhanced leptin mRNA as well as leptin protein in mouse adipose tissue but growth hormone administration (0.3 or 0.6 units/mouse) had no effect on them. Leptin protein level in sera of mice injected with insulin or growth hormone was not significantly different from that of control group. These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.
Adipocytes/*metabolism ; Animal ; Cells, Cultured ; Culture Media/analysis ; Dexamethasone/pharmacology ; Dose-Response Relationship, Drug ; Epinephrine/pharmacology ; Gene Expression Regulation/*drug effects ; Growth Hormone/blood/*pharmacology ; Hypoglycemic Agents/blood/*pharmacology ; Insulin/blood/*pharmacology ; Leptin/blood/genetics/*metabolism ; Male ; Mice ; Mice, Inbred ICR ; RNA, Messenger/analysis ; Transcription, Genetic/drug effects

This study was conducted to define the molecular mechanism of fasting-induced down-regulation of neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN). Rats were adrenalectomized (ADX), and then either underwent food deprivation or received varying doses of dexamethasone for 48 h. The brain tissues were processed for NADPH-diaphorase (NADPH-d) staining, a histochemical marker of nNOS enzyme activity. Both the ADX and the sham operated rats showed a significant weight loss after 48 h of food deprivation. Food deprivation decreased the number of NADPH-d containing cells in the PVN of sham rats, however, not in the ADX rats. Dexamethasone dose- dependently decreased NADPH-d cells in the PVN of ADX rats. The effect of ADX or dexamethasone was limited to the parvocellular subdivision of PVN. These results suggest that the adrenal glucocorticoids may down-regulate nNOS expression in the PVN during food deprivation.
*Adrenalectomy ; Animals ; Biological Markers ; Dexamethasone/blood/pharmacology ; Down-Regulation/physiology ; Fasting/*physiology ; Food Deprivation/physiology ; Glucocorticoids/blood/pharmacology ; Male ; NADPH Dehydrogenase/*metabolism ; Nitric-Oxide Synthase/*metabolism ; Paraventricular Hypothalamic Nucleus/*enzymology ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't

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