Objective To search novel genes or pathways involved in the recovery process after restraint stress in rats. Methods We compared the hypothalamus transcriptional profiles of two different recovery patterns (fast reco...Objective To search novel genes or pathways involved in the recovery process after restraint stress in rats. Methods We compared the hypothalamus transcriptional profiles of two different recovery patterns (fast recovery vs slow recovery) from restraint stress in rats using oligonucleotide microarray, the recovery pattern was determined by the decrement of plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels during one hour recovery period after stress. A real-time quantitative RT-PCR was applied to validate the differential expressed genes. Results Analysis of the microarray data showed that most of genes were not differentially expressed between fast recovery group and slow recovery group. Among the differentially expressed genes we found that talin, together with serine/threonine protein phosphatase PPl-beta catalytic subunit (PP-1B) and integrin α-6 precursor (VLA-6) genes, were at least 1.5 fold upregulated in the fast recovery group, while junctional adhesion molecule 1 (F11r) was 1.5 fold down-regulated in the fast recovery group. Conclusion The results implied that integrin signaling pathway may be involved in the recovery from restraint stress in rats. The present study provided a global overview of hypothalamus transcriptional profiles during the process of recovery from the restraint stress in rats. The integrin signaling pathway seems to be involved in the recovery process, which deserves further study to clarify the integrin-mediated recovery mechanism after restraint stress.展开更多
Objective Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was pe...Objective Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by videoEEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00 a.m.), sleep (00:00 a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures (P 〈 0.001). Such changes did not occur in the control group (P 〉 0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P 〉 0.05). Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.展开更多
AIM: To investigate the effect and mechanism of electro-acupuncture lEA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into norm...AIM: To investigate the effect and mechanism of electro-acupuncture lEA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum (CR). An abdominal withdrawal reflex (AWR) scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells (MC), changes of substance P (SP) and substance P receptor (SPR) in colon and change of corticotropin-releasing hormone (CRH) in hypothalamus. RESULTS: The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION: EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.展开更多
AIM:To investigate whether peripheral corticotropin releasing hormone (CRH), which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis. METHOD...AIM:To investigate whether peripheral corticotropin releasing hormone (CRH), which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis. METHODS:We measured mucosal myeloperoxidase (MPO) activity as a marker of inflammation, plasma CRH level, and abdominal withdrawal reflex (AWR) to colorectal distension as a visceral nociceptive response at 2, 7 and 14 d after the induction of colitis with 4% acetic acid. RESULTS:Colonic inflammation, quantified by MPO activity, significantly increased on d 2 and subsided thereafter, which indicated a resolution of inflammation within 7 d. On the contrary, plasma CRH level and AWR score were increased on d 2, remained high on d 7, and returned to control level on d 14. Intraperitoneal injection of a CRH antagonist, astressin (30 μg/kg), significantly attenuated the post-inflammatory visceral hypersensitivity on d 7. Furthermore, intraperitoneal administration of CRH (3 and 10 μg/kg) mimicked the post-inflammatory visceral hypersensitivity in naive rats. CONCLUSION:These results suggest that increased peripheral CRH mediates the enhanced visceral nociception in rats recovered from experimental colitis.展开更多
AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was adm...AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.展开更多
Objective To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH) -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI po...Objective To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH) -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confn'med Cushing's disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) on a 1. 5 Tesla MR/scanner, and dynamic enhanced MR/was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. Results Preoperative MR/revealed normal results in 41 ( 15.4% ) cases, microadenoma in 179 (67. 3% ), macroadenoma in 42 ( 15.8% ), and huge adenoma in 4 ( 1.5% ). Pituitary apoplexy was found in 13 (4.9%) cases. Positive rate of ACTH-secreting adenomas was 84.6% (225/266) on MR/scans, and that of small microadenomas was 87.2% (34/39) on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing's disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6. 4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results (90% vs. 87. 8%, P =0. 904). Conclusions Enhanced coronal pituitary MR/ is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MR/may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MR/results indicating presence or absence of microadenoma.展开更多
AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play...AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRa and GRp in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n - 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRa and GRp expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRa and GRp expression. Both positive association between GRa expression and the response of UC to GC and strong negative association between GRp expression and the response of UC to GC were identified. There was no significant association between GRa/GRp expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRa and GRp may play an important role in the action of GC, and that GRp functions as a dominant negative inhibitor of GRa. Expression of GRa and GRp in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.展开更多
Objective: To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation (SEM-rTMS) and conventional rTMS (C-rTMS) on the activity of hypothalamic-pituitary-adren...Objective: To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation (SEM-rTMS) and conventional rTMS (C-rTMS) on the activity of hypothalamic-pituitary-adrenal (HPA) axis in patients with depression. Methods: In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS (n=57), C-rTMS (n=55) or sham rTMS (n=52) for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (CORT) were measured, and the 24-item Hamilton Depression Rating Scale (HAMD-24) was used for assessment. Results: The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group (P〈0.05). The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly (P〈0.05). There was a significant positive correlation between the HAMD-24 scores and plasma ACTH (n=240, r=0.105, P=0.048) and CORT concentrations (n-240, r=0.126, P=0.023) in the patients with depression before and after treatment. Conclusion: The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. (This trail was registered. No: ChiCTR-TRC-00000465)展开更多
Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhib...Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocorticoid receptor, and enhances glucocorticoid receptor transactivation ability.展开更多
AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seede...AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seeded into 24-well culture plates and grown for 3 d.Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291),Bacteroides vulgatus (B.vulgatus) (JCM5856),Escherichia coli (JCM1649),or Fusobacterium varium (F.varium) (ATCC8501) were added to the cells except for the control well,and incubated for 2 h.After incubation,we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells,and compared these values with controls.RESULTS:The level of CRF secretion by control dendritic cells was 40.4±6.2 pg/mL.The CRF levels for cells incubated with F.varium and B.vulgatus were significantly higher than that of the control (P<0.0001).CRF mRNA was present in the control sample without bacteria,and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F.varium caused the greatest increase in CRF mRNA expression.CONCLUSION:Our results suggest that dendritic cells produce CRF,a process augmented by commensal bacteria.展开更多
On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental pertur...On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.展开更多
Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order...Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.展开更多
Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete E...Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist , and Tamoxifen, an ERa-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERa.展开更多
To investigate the significance of bone mineral changes in the pathogenic process of steroid-induced osteonecrosis in rabbits. Methods: Seventy adult female Japanese White rabbits were randomly divided into five grou...To investigate the significance of bone mineral changes in the pathogenic process of steroid-induced osteonecrosis in rabbits. Methods: Seventy adult female Japanese White rabbits were randomly divided into five groups Animals in steroid group received an intramuscular injection of methylprednisolone acetate (4 mg/kg) once a week, and killed in four different time after first treatment. Animals in control group received an intramuscular injection with the same volume of normal saline, while 150 kU penicillin was injected twice a week for preventing infection in all groups. The contents of serum calcium (Ca) and phosphorus (P) were determined and the bone mineral densities of the femoral head and neck were measured at the 2nd, 4th, 8th and 10th weeks after first treatment. Meanwhile the general condition such as weight, spirit and hair of rabbits was observed. Results: Compared with the control group, the weight of rabbits in steroid group lost since the first week, and progressively aggravated; the bone mineral density of the femoral head and neck was lowered since the 2nd and 4th week respectively (P〈0.05, P〈0.01), and lowered more quickly in femoral neck than in femoral head. In steroid group, the bone mineral density of the femoral neck at the 10th week was significantly lower than that at the 8th week (P〈0.05) Compared with the control group, the serum levels of Ca and P in steroid group were lowered since the 2nd week (P〈0.05, P〈0.01). In steroid group, the serum Ca level at the 10th week was lower than that at the 8th week, and the serum P level waslowered more quickly than Ca level was. Conclusion: Osteonecrosis appears in rabbits shortly after corticoids are first administered, and osteonecrosis in rabbits is chronologically associated with the onset of hypocalcaemia, hypophosphatemia and lowered bone mineral density. Steroid-induced osteonecrosis may be relevant to bone mineral loss and density lowering of the femoral head and neck.展开更多
文摘Objective To search novel genes or pathways involved in the recovery process after restraint stress in rats. Methods We compared the hypothalamus transcriptional profiles of two different recovery patterns (fast recovery vs slow recovery) from restraint stress in rats using oligonucleotide microarray, the recovery pattern was determined by the decrement of plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels during one hour recovery period after stress. A real-time quantitative RT-PCR was applied to validate the differential expressed genes. Results Analysis of the microarray data showed that most of genes were not differentially expressed between fast recovery group and slow recovery group. Among the differentially expressed genes we found that talin, together with serine/threonine protein phosphatase PPl-beta catalytic subunit (PP-1B) and integrin α-6 precursor (VLA-6) genes, were at least 1.5 fold upregulated in the fast recovery group, while junctional adhesion molecule 1 (F11r) was 1.5 fold down-regulated in the fast recovery group. Conclusion The results implied that integrin signaling pathway may be involved in the recovery from restraint stress in rats. The present study provided a global overview of hypothalamus transcriptional profiles during the process of recovery from the restraint stress in rats. The integrin signaling pathway seems to be involved in the recovery process, which deserves further study to clarify the integrin-mediated recovery mechanism after restraint stress.
文摘Objective Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by videoEEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00 a.m.), sleep (00:00 a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures (P 〈 0.001). Such changes did not occur in the control group (P 〉 0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P 〉 0.05). Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.
基金Supported by Open Fund of Key Laboratory of Acupuncture Combined with Medication (Nanjing University of TCM), Ministry of Education, No. KJA200809Shanghai Rising-Star Program, No. 08QA14064Shanghai Leading Academic Discipline Project, No. S30304
文摘AIM: To investigate the effect and mechanism of electro-acupuncture lEA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum (CR). An abdominal withdrawal reflex (AWR) scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells (MC), changes of substance P (SP) and substance P receptor (SPR) in colon and change of corticotropin-releasing hormone (CRH) in hypothalamus. RESULTS: The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION: EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.
文摘AIM:To investigate whether peripheral corticotropin releasing hormone (CRH), which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis. METHODS:We measured mucosal myeloperoxidase (MPO) activity as a marker of inflammation, plasma CRH level, and abdominal withdrawal reflex (AWR) to colorectal distension as a visceral nociceptive response at 2, 7 and 14 d after the induction of colitis with 4% acetic acid. RESULTS:Colonic inflammation, quantified by MPO activity, significantly increased on d 2 and subsided thereafter, which indicated a resolution of inflammation within 7 d. On the contrary, plasma CRH level and AWR score were increased on d 2, remained high on d 7, and returned to control level on d 14. Intraperitoneal injection of a CRH antagonist, astressin (30 μg/kg), significantly attenuated the post-inflammatory visceral hypersensitivity on d 7. Furthermore, intraperitoneal administration of CRH (3 and 10 μg/kg) mimicked the post-inflammatory visceral hypersensitivity in naive rats. CONCLUSION:These results suggest that increased peripheral CRH mediates the enhanced visceral nociception in rats recovered from experimental colitis.
文摘AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.
文摘Objective To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH) -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confn'med Cushing's disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) on a 1. 5 Tesla MR/scanner, and dynamic enhanced MR/was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. Results Preoperative MR/revealed normal results in 41 ( 15.4% ) cases, microadenoma in 179 (67. 3% ), macroadenoma in 42 ( 15.8% ), and huge adenoma in 4 ( 1.5% ). Pituitary apoplexy was found in 13 (4.9%) cases. Positive rate of ACTH-secreting adenomas was 84.6% (225/266) on MR/scans, and that of small microadenomas was 87.2% (34/39) on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing's disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6. 4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results (90% vs. 87. 8%, P =0. 904). Conclusions Enhanced coronal pituitary MR/ is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MR/may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MR/results indicating presence or absence of microadenoma.
文摘AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRAAA and GRp) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRa and GRp in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n - 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRa and GRp expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRa and GRp expression. Both positive association between GRa expression and the response of UC to GC and strong negative association between GRp expression and the response of UC to GC were identified. There was no significant association between GRa/GRp expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRa and GRp may play an important role in the action of GC, and that GRp functions as a dominant negative inhibitor of GRa. Expression of GRa and GRp in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.
基金Supported by the Social Development Guide Projects of Science and Technology Committee of Jiangsu Province in 2005 (BS2005629)"The Six Major Expert Peaks" Projects of Jiangsu Provincial Government in 2006 [Surentong (2006) 174]
文摘Objective: To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation (SEM-rTMS) and conventional rTMS (C-rTMS) on the activity of hypothalamic-pituitary-adrenal (HPA) axis in patients with depression. Methods: In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS (n=57), C-rTMS (n=55) or sham rTMS (n=52) for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (CORT) were measured, and the 24-item Hamilton Depression Rating Scale (HAMD-24) was used for assessment. Results: The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group (P〈0.05). The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly (P〈0.05). There was a significant positive correlation between the HAMD-24 scores and plasma ACTH (n=240, r=0.105, P=0.048) and CORT concentrations (n-240, r=0.126, P=0.023) in the patients with depression before and after treatment. Conclusion: The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. (This trail was registered. No: ChiCTR-TRC-00000465)
文摘Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocorticoid receptor, and enhances glucocorticoid receptor transactivation ability.
基金Supported by Grants in Aid for Scientific Research (C) from the Japanese Ministry of Education,Culture,Sports,Science and Technology,No. 17590679
文摘AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seeded into 24-well culture plates and grown for 3 d.Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291),Bacteroides vulgatus (B.vulgatus) (JCM5856),Escherichia coli (JCM1649),or Fusobacterium varium (F.varium) (ATCC8501) were added to the cells except for the control well,and incubated for 2 h.After incubation,we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells,and compared these values with controls.RESULTS:The level of CRF secretion by control dendritic cells was 40.4±6.2 pg/mL.The CRF levels for cells incubated with F.varium and B.vulgatus were significantly higher than that of the control (P<0.0001).CRF mRNA was present in the control sample without bacteria,and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F.varium caused the greatest increase in CRF mRNA expression.CONCLUSION:Our results suggest that dendritic cells produce CRF,a process augmented by commensal bacteria.
文摘On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.
文摘Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.
基金Supported by National Natural Science Foundation of China(No.39870300)
文摘Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist , and Tamoxifen, an ERa-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERa.
文摘To investigate the significance of bone mineral changes in the pathogenic process of steroid-induced osteonecrosis in rabbits. Methods: Seventy adult female Japanese White rabbits were randomly divided into five groups Animals in steroid group received an intramuscular injection of methylprednisolone acetate (4 mg/kg) once a week, and killed in four different time after first treatment. Animals in control group received an intramuscular injection with the same volume of normal saline, while 150 kU penicillin was injected twice a week for preventing infection in all groups. The contents of serum calcium (Ca) and phosphorus (P) were determined and the bone mineral densities of the femoral head and neck were measured at the 2nd, 4th, 8th and 10th weeks after first treatment. Meanwhile the general condition such as weight, spirit and hair of rabbits was observed. Results: Compared with the control group, the weight of rabbits in steroid group lost since the first week, and progressively aggravated; the bone mineral density of the femoral head and neck was lowered since the 2nd and 4th week respectively (P〈0.05, P〈0.01), and lowered more quickly in femoral neck than in femoral head. In steroid group, the bone mineral density of the femoral neck at the 10th week was significantly lower than that at the 8th week (P〈0.05) Compared with the control group, the serum levels of Ca and P in steroid group were lowered since the 2nd week (P〈0.05, P〈0.01). In steroid group, the serum Ca level at the 10th week was lower than that at the 8th week, and the serum P level waslowered more quickly than Ca level was. Conclusion: Osteonecrosis appears in rabbits shortly after corticoids are first administered, and osteonecrosis in rabbits is chronologically associated with the onset of hypocalcaemia, hypophosphatemia and lowered bone mineral density. Steroid-induced osteonecrosis may be relevant to bone mineral loss and density lowering of the femoral head and neck.