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Objective To observe the expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampi of rats stressed by restraint,and adjustments to 11β-HSD1 expression in response to electroacupuncture.The mechanisms of adjustment of the hypothalamic-pituitary-adrenal axis(HPA) to electroacupuncture were also studied.Methods Rats were randomly divided into a control group,a group stressed by restraint and an electroacupuncture group.The rats in the control group received no treatment. The rats in the strssd group were put into a small columnar cage and their hind legs tied outside the cage. The electroacupuncture group, in addition to being restrained,received electroacupuncture at the Zusanli acupoints on both sides of their bodies. The rats were then sacrificed and their hippocampi were isolated and lysed. The expression of 11β-HSD1 in each hippocampus were observed using the Western blotting technique. Results The leves of expression of 11β-HSD1 in the hippocampi of the restrained group were significantly higher than those in the control group.After electroacupuncture,11β-HSD1 expression in the hippocampus increased further and lasted 3 h. Conclusion Electroacupuncture at the Zusanli acupoints (ST36) can increase 11β-HSD1 expression in the hippocampus of stressed rats, and this adjustment may be related to the HPA axis' negative feedback function.
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Objective To observe the effects of restrain stress on the phosphorylation of p38 mitogen-activated protein kinase ~MAPK) in rat hypothalamus and the regulation effects of electroacupuncture on the phosphorylated-p38 MAPK. Methods Twenty-eight rats were randomly divided into a control group, a restrain stress group and a restrain stress plus electroacupuncture group. The Western blot was employed to observe the changes of phosphorylated-p38MAPK in the three groups. Results Western blot analysis demonstrated a higher level of phosphorylation of p38 MAPK in the hypothalamus from restrain stress group than that from control. The higher level of phosphorylated-p38 MAPK could last for 3 hours after stress was relieved. The level of phosphorylated-p38MAPK could be decreased to some extent when the Zusanli acupoint of the restrained rat was acupunctured. The effects of electroacupuncture of Zusanli on phosphorylated-p38MAPK in hypothalamus could still be retained although the electroacupuncture was ended for 3 hours. Conclusion The results suggested that restrain stress can lead to a higher level of phosphorylation of p38 MAPK in hypothalamus, which might be an important event in the response of hypothalamic-pitutary-adrenal ~HPA) axis. The mechanism underlying the regulation of HPA by electroacupuncture might be (related) to the regulation of phosphorylated-p38 MAPK in hypothalamus.
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Objective To investigate the clinical features of myasthenia gravis (MG) in elderly people. Methods Elderly patients among all MG patients observed from February 1977 to February 2003 were respectively reviewed. Results Of 3010 MG patients,232(7.7%) were identified with the onset of the disease after or at the age of 60,and males were more than females with the ratio of 1.3∶1. The first and most commonly seen symptom in the elderly people after MG onset were ocular manifestation,occurring in 79.3%. Bulbar symptoms(12.9%) such as dysarthria and swallowing difficulties were the following symptoms. The systemic form (62.9%) were significantly more than ocular form (37.1%). There were less MG patients with autoimmunity diseases such as thyroid diseases associated with MG than that with the other senile diseases,and the myasthenia crisis were even less in the elderly patients with MG. However,it was found that more MG patients with thymoma than with other thymus abnormality. Conclusions The elderly MG patients had its distinctive clinical features. It is beneficial for diagnosing and treating the MG patients in the elderly people by understanding these clinical features.
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Objective To evaluate the long-term outcomes of immunosuppressive agents used for myasthenia gravis(MG) patients with disease onset after or at 60. Methods Long-term outcome was evaluated in 99 cases with following-up longer than 1 year. Remission, pharmacological remission, and marked improvement were considered as good results or good long-term outcome. Results All good results were recorded in 79 MG patients (79.8%) receiving immunosuppressive treatments. 48 patients had been treated with glucocorticoids (GC) alone, of them, 35(72.9%) achieved good results. 8 of them having a complete remission for 18 to 67 months (averaging (54.8?19.8) months). 16 patients got pharmacological remission for 7 to 37 months (averaging (15.7?8.0) months). MG patients in different gender had different responses to GC. The good long-term outcome was found in 83.3% (25/30) males and only 55.6% (10/18) in females with GC therapy. There was a rate statistically higher in male than in female patients (P
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Objective:To study the toxicity of 11 dehydrocorticosterone on hippocampal neurons and to determine whether 11? hydroxysteroid dehydrogenase (11? HSD1) is involved in the neurotoxity. Methods:Western blotting, radiometric enzyme activity assay and MTT assay were employed in this study. Results:Both 11? HSD1 protein and bioactivity were positive in the hippocampal neurons as demonstrated by Western blotting and radiometric enzyme activity assay. At concentration of 10 -6 mol/L, 11 dehydrocorticosterone was neurontoxic to hippocampal neurons cultured in serum free DMEM medium. This neurotoxic effect of 11 dehydrocorticosterone was blocked by 11? HSD1 inhibitor carbenoxolone (CBX) and glucocorticoid receptor (GR) antagonist RU38486, but not by mineralcocorticoid receptor (MR) antagonist spironolatone. Corticosterone and its derivative 11 dehydrocorticosterone up regulated 11? HSD1 level. Conclusion:11 dehydrocorticosterone has toxicity on hippocampal neurons, and it can be blocked by CBX, suggesting 11? HSD1 may convert biologically inactive 11 dehydrocorticosterone to active corticosterone. The up regulation of 11? HSD1 by glucocorticoids in return exaggerates the neurotoxic effect of corticosterone, which may play a positive role in the delayed neuron death during stress.
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Objective:To observe the imprinting effects of prenatal overexposure to glucocorticoids on 11?-hydroxysteroid dehydrogenase type 1(11?-HSD1) expression in the rat offspring liver. Methods: Pregnancy was determined by examining vaginal smear. Eight pregnant rats were divided into dexamethasone(DEX) group and normal saline(NS) group at random with each group containing 4 rats.DEX group was given subcutaneous injection of DEX [0.05 mg/(kg?d)] and NS group was given injection of NS.Western blot was adopted to determine 11?-HSD1 protein in the liver of the offspring at the age of 4 months;RT-PCR was used to determine 11?-HSD1 mRNA and hepatic phosphoenolpyruvate carboxykinase(PEPCK) mRNA;and glucose oxidase method was used to measure the blood glucose concentration. Results: Western blot and RT-PCR showed that prenatal overexposure to DEX increased the expression of 11?-HSD1 protein and mRNA in the liver of the female offsprings at 4 months old, but not in male offsprings.Prenatal overexposure to DEX also increased the expression of PEPCK mRNA and blood glucose level in the female offsprings at 4 months old.Conclusion:Our study suggests that prenatal overexposure to glucocorticoids throughout gestation can imprint the expression of 11?-HSD1 in rat offsprings liver, which may lead to the PEPCK overexpression and blood glucose elevation.Development of diabetes may be induced in individuals overexposed to glucocorticoids during fetal period.
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Objective This study was designed to study the distribution and developmental changes of 11?\|hydroxysteroid dehydrogenase 1(11?\|HSD1) in the neonatal rat brain. Methods Immunohistochemistry and Western blot were used to observe the distribution and changes of 11?\|HSD1 protein levels in the neonatal rat brain. Results 11?\|HSD1 protein was highly expressed in all layers of the cerebral cortex as well as all sub\|regions of the hippocampus by immunohistochemistry.Western blot analysis showed that the expression of 11?\|HSD1 protein in the neonatal rat cortex,hippocampus and hypothalamus was higher during the first two weeks of life,but started to fall from 15th day after birth.Conclusion\ The expression pattern of 11?\|HSD1 protein in different brain areas in the neonatal rat suggests that 11?\|HSD1 protein may play an important role in the development and maturation of the brain.\;[