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Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.
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Background: Colonoscopy has been widely applied in clinic because of its value in screening, diagnosis and treatment of colorectal diseases. Discomfort and pain account for a great part of incomplete intubation during sedation-free colonoscopy. Aims: To identify the predictive factors for difficult sedation-free colonoscopy. Methods: Patients aged 18-80 years old undergone sedation-free colonoscopy at the Tenth People's Hospital of Tongji University from January to December in 2017 were enrolled. The clinical data and medical history were collected. Each patient completed the Eysenck Personality Questionnaire (EPQ) with the help of nurse before colonoscopy. Sedation-free colonoscopy was performed by experienced endoscopist. The Ottawa bowel preparation scale and Visual Analog Scale were used to evaluate the quality of bowel cleansing and pain during the procedure. Results: The total cecum intubation rate was 97.1% (198/204), and 192 patients completing the EPQ were enrolled for analyses. Twenty-four patients had a difficult colonoscopy (intubation time prolonged to >10 min). By univariate analysis, gender, age, body mass index (BMI), history of surgery, pain level and score of Extraversion-Introversion Scale of EPQ (EPQ-E) were associated with difficulty during colonoscopy (all P<0.05). Multivariate analysis revealed that history of pelvic surgery was a risk factor for difficult colonoscopy (OR=6.833, 95% CI: 2.396-19.488, P<0.001), whereas overweight (OR=0.190, 95% CI: 0.038-0.962, P=0.045) and score of EPQ-E ranged from 8-15 (OR=0.367, 95% CI: 0.150-0.896, P=0.028) were protective factors. Conclusions: History of pelvic surgery, lower BMI and extraversion or introversion personality may increase the difficulty during sedation-free colonoscopy. EPQ-E might be used for selecting candidates of sedation-free colonoscopy when it is performed by an inexperienced endoscopist.
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Objective:To screen the risk factors of psychology problems and quality of life of patients with inflammatory bowel disease (IBD) by questionnaire, and to explore the impact of anxiety and depression on the quality of life and disease of IBD patients, in order to guide the treatment of IBD.Methods:From June 15 to July 15 in 2019, 171 IBD patients diagnosed in the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University in Shanghai were investigated by internet questionnaire. Finally 136 IBD patients (IBD group) were enrolled. During the same period 121 healthy individuals with no difference in age and gender were selected as healthy control group. IBD clinical questionnaire, the generalized anxiety disorder (GAD)-7, patient health questionnare (PHQ)-9 depression screening and the short form 36-item health survey (SF-36) quality of life evaluation scale were used in IBD group. General situation questionnaire, GAD-7, PHQ-9 and SF-36 scale were conducted in healthy control group. Chi-square test, Binary logistic regression analysis, Ordinal logistic regression analysis, and Pearson correlation analysis were used for statistical analysis.Results:In IBD group, 87(64.0%) were males and 49(36.0%) were females; 25 cases (18.4%) were ulcerative colitis (UC) and 111 cases (81.6%) were Crohn′s disease (CD); and the median age was (32(26, 40)) years old. In healthy control group, 68 (56.2%) were males and 53(43.8%) were females; the median age was (32(26, 37)) years old. The incidence of anxiety in UC patients and CD patients was 64.0%(16/25) and 64.9%(72/111), respectively, and the incidence of depression in UC and CD was 72.0%(18/25) and 58.6%(65/111), respectively. There were no significant differences in the incidence of anxiety and depression between UC patients and CD patients (both P>0.05). Role-emotional (odds ratio ( OR)=0.965, 95% confidence interval ( CI) 0.937 to 0.994, P=0.017) and mental health ( OR=0.940, 95% CI 0.896 to 0.985, P=0.010) may be the independent factors of depression. Physiological function ( OR=1.040, 95% CI 1.010 to 2.730, P=0.022) was the independent factors of depression. There was no significant correlation between the duration of disease and the quality of life ( P>0.05). There was no significant correlation between disease activity and quality of life, however it was related to physiological function ( r=0.15, P=0.046). The physiological function of IBD patients in remission stage was better than that of patients in activity stage. Depression was negatively correlated with quality of life ( r=-0.55, P<0.01), and with a linear relationship ( r=19.429, intercept was 744.455, P<0.01). Anxiety was not correlated with quality of life ( P>0.05). Depression was negatively correlated with changes of physical function, role-physical function, physical pain, general health, vitality, social function, emotional function, mental health, and reported health transition ( r=-0.234, -0.358, -0.454, -0.449, -0.566, -0.485, -0.441, -0.597, and -0.193, all P<0.05). Conclusions:IBD patients are prone to anxiety and depression. Depression is negative correlated with quality of life. It is very important to screen and intervene mental disorders in IBD patients, especially in patients with depression. Controlling the activity of IBD and relieving the clinical symptoms of patients may be effective in improving anxiety and depression. The treatment of IBD itself is the basis of IBD psychotherapy.
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Objective To investigate the independent association of serum Fetuin-B with metabolic syndrome in obese Chinese adults.Methods Cross-sectional data on socio-demographic,lifestyle,clinical characteristics, and serum Fetuin-B were collected for 1 318 Chinese adults with central obesity.Associations of serum Fetuin-B with metabolic syndrome and insulin resistance were analyzed using multivariable Logistic regression analysis.Results A total of 820(62.2%)individuals were identified as metabolic syndrome.Subjects with metabolic syndrome showed significantly increased levels of serum Fetuin-B than those with non-metabolic syndrome[(4.18 ±1.39 vs 4.02 ± 1.35)μg/ml,P=0.043].Increased serum Fetuin-B were significantly associated with increased fasting plasma glucose and insulin levels, as well as prevalences of non-alcoholic fatty liver disease(NAFLD)and insulin resistance.After adjustment for potential confounders, serum Fetuin-B was significantly associated with increased risks of metabolic syndrome and insulin resistance(OR=1.19,95%CI 1.06-1.34,P=0.004;OR=1.15,95%CI 1.01-1.30,P=0.031 respectively).Conclusion Serum Fetuin-B level was significantly associated with NAFLD;and elevated serum Fetuin-B was significantly associated with increased risk of metabolic syndrome.
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Objective To study the strain difference in response to the antidepressant fluoxetine in mouse tail suspension test.Methods Two outbred mouse strains (KM and ICR) and three inbred mouse strains (C57BL/6,Balb/c and DBA/2) were used in this study.They were treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine or saline and the immobility time in tail suspension test was recorded.Results There was significant difference of baseline immobility time among different stains with C57BL/6 the most immobile((145.0 ±16.8) s) and DBA/2 the least ((34.5 ± 6.1)s).Fluoxetine significantly decreased the immobility time in C57BL/6 ((116.0 ± 10.3) s vs (145.0 ± 16.8) s) of control),Balb/c ((44.3 ± 6.2) s vs (75.3 ± 10.3) s) of control) and DBA/2 mice ((16.6 ± 4.3) s vs (34.5 ± 6.1) s) of control),while the immobile time of KM and ICR mice was not influenced by fluoxetine.Conclusion The effects of fluoxetine in tail suspension test are strain dependent.Fluoxetiue exhibits antidepressant effects in C57BL/6,Balb/c and DBA/2 mice,but not in KM and ICR mice.
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Objective To investigate the expression of microRNA (miRNA)-10a in the intestinal mucosa,serum and peripheral blood mononuclear cell (PBMC) of patients with inflammatory bowel disease (IBD) and explore its role and relevance in the pathogenesis of the disease.Methods The intestinal or colonic mucosal biopsy specimens of nine active ulcerative colitis (UC) patients,11 active Crohn's disease (CD) patients and eight patients with negative colonoscopy result as control were collected.The sera of 12 active UC patients,13 active CD patients and nine healthy controls were collected.The PBMC of nine active UC patients,11 active CD patients and eight healthy controls were collected.The expression of miRNA-10a in the intestinal mucosa,sera and PBMC and the expression of IL-12/IL-23 p40 in the intestinal mucosa were detected by real-time polymerase chain reaction (PCR).Each 8 cases of active UC and CD patients were collected.The intestinal mucosa before infliximab (IFX) treatment and six weeks after three times of IFX treatment were collected.And at same time,the intestinal mucosa of 11 active UC patients and 10 active CD patients were collected and cultured for 18 hours stimulated with IFX in vitro and then the expression of miRNA-10a in the intestinal mucosa was tested.One-way analysis of variance was used for comparison in three samples.Paired t-test was used for two samples comparison.Spearman test was used for correlation analysis.Results Compared with healthy controls,the expression of miRNA-10a in the intestinal mucosa,serum and PBMC of UC and CD patients significantly decreased (F=38.45,30.46 and 14.74,all P＜0.05).There was no statistic significance between UC and CD groups.The expression of IL-12/IL-23 p40 in the intestinal mucosa of UC and CD patients significantly increased (F=32.90,P＜0.05).The expression of IL-12/IL-23 p40 was negatively correlated with the expression of miRNA-10a in the intestinal mucosa of CD patients.After three times of IFX treatment,the expression of miR-10a in the intestinal mucosa of IBD patients significantly increased (t=3.341,3.382,both P＜0.05).After stimulated with IFX in vitro,the expression of miRNA-10a in the intestinal mucosa significantly increased (t=3.095,7.193,both P＜0.05).Conclusions miRNA-10a was closely correlated with the inflammation of IBD patients and with the role of targeting IL-12/IL-23 p40.miRNA-10a might be a new target for the IBD treatment.
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Objective To investigate the changes of interleukin-21 (IL 21) and interleukin-21 receptor (IL 21R) expression level in Crohn's disease (CD) patients before and after accepted infliximab (IFX) treatment.Methods From June 2009 to July 2011,twenty-two CD patients met the research criteria were recruited at Tenth People's Hospital of Tongji University.Patients were treated with infliximab at weeks 0,2,6,and 16 healthy individuals were set as healthy control group at same time.Peripheral blood of healthy control group was taken at regular physical examination and blood of CD patients was taken before treatment and 10 weeks after treatment,intestinal mucosa biopsy samples were taken under colon endoscopy examination.The changes of Crohn's disease activity index (CDAI),erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) in CD patients were observed.The change of IL-21R in peripheral blood CD4+ T lymphocytes was detected by flow cytometry.The change of IL-21 expression at mRNA level in intestinal mucosa was determined by realtime quantitative polymerase chain reaction (PCR).The data were analyzed by t test.Results Before treatment,the level of IL21R in peripheral blood CD4+ T lymphocytes of CD patients (12.25％±3.25％) and the expression of IL-21 at mRNA level in inflamed intestinal mucosa (1.38±0.32) were both significantly higher than those of healthy controls (4.25 ％ ± 1.41％,0.44±0.18),the differences were statistically significant (F=15.88,6.75 ; both P＜0.05).At 10th week,the level of IL-21R in peripheral blood CD4+ T lymphocytes of CD patients (8.12％ ± 2.05％) and the expression of IL-21 at mRNA level in intestinal mucosa (0.77 ± 0.24) were both significantly lower than those before treatment,the differences were statistically significant ( t=4.880,8.019; both P＜0.01).Before treatment,ESR,CRP and CDAI of CD patients was (46.8±11.4) mm/1 h,(52.4±11.5) mg/L and 319±74,which was (23.5±9.0) mm/1 h,(11.6±4.6) mg/L and 113±42 after treatment,the differences were statistically significant (t=9.485,16.458,11.100; all P＜0.05).Conclusion The IL-21 expression of active CD patients decreases after IFX treatment,which indicates that IL-21 may involve in IFX induced clinical remission of active CD.
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Objective To observe The liver lipogenic gene expression of animal model of phlegm and dampness syndrome. Methods According to the theory "Obese people have much more phlegm and dampness", the animal model of phlegm and dampness was built by high fat feeding. After 10 weeks' high fat feeding, we examined liver HE slice, the level of lipids in the normal and model group rats .The liver lipogenic gene expression including LXRα, SREBP-1c, and FAS were detected by fluorescence real time quantative PCR. Results Compared with that of the normal group rat, there was increasing lipids both in serum and liver in the model rats. There was typical appearance of fatty accumulation in the liver cells examined by liver HE staining. The expression of SREBP-Ic and FAS was much higher in phlegm and dampness group than that in the normal group, although there was no difference in the expression of LXRα. Conclusion The fatty accumulation of liver cell in phlegm and dampness group has a close relation to the enhancement of the liver lipoganic gene expression.
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Non-alcoholic fatty liver (NAFLD) is one of the most commonly liver diseases. Food control and proper amount of physical exercise are reliable measures to treat it. TCM has accumulated plenty experiences and found solid basis in treating NAFLD. In this article, we made a summarization and study on mechanism and effective substance of TCM in treating NAFLD clinically.
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Objective To investigate the effect of diltiazem, one of calcium antagonists, on the function of rat beta cells and the re- lease of insulin induced by D860. Methods Intravenous glucose tolerance test (IVGTY) was conducted to assess beta-cell function of rats among control, dihiazem, D860, and dihiazem plus D860 groups, followed by treatment with dihiazem and D860 for 4 weeks respectively. Another IVGTT was carded out at the end of the study. Results The data showed that diltiazem could inhibit insulin released from normal SD rats. Moreover, it reduced the hypoglycemic effect promoted by D860. However, in long term, the rise of blood sugar in rats treated with D860 respectively was not found. Conclusion Diltiazem did not impair beta cells function and interfere the hypoglycemic effect of D860 in rats in long time.
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Summary: To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruend's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23 %, 58.82 % and 63.16 % respectively, which were significantly higher than those of MG group and NS group (40.00 %, 40.00 %, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.
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BACKGROUND: It is recently found that some kinds of antibiotics can aggravate the obstruction of neuromuscular junction(NM J) transmission,exacerbate myasthenia gravis (MG). Hitherto, there are few reports about the effect of antibiotics on transitive function on animal models. Along with the appearance of new antibiotics, the effects of the antibiotics on NMJ transitive function need to be further observed.OBJECTIVE: To investigate the effect of aminoglycoside antibiotics, fluoroquinolone antibiotics and cephalosporin antibiotics on the transitive function of NMJ in MG, and to provide an experimental basis for using those antibiotics securely in clinic and for selecting those antibiotics to treat MG properly.DESIGN: Randomized controlled study based on experimental animals.SETTING: Department of nosocomial infection, neurology and pharmacy in a university hospital.MATERIALS: The experiment was conducted at the Neurological Institute of Tongji Medical College, Huazhong University of Science and Technology from March 2002 to January 2003. Totally 150 healthy female C57BL/6mice, 6 - 8 weeks old, weighting 18 - 20 g, were divided randomly into 4groups: normal group( n = 10), MG group( n = 10), saline group( n = 10)and antibiotics group( n = 120) . Mice in antibiotics group were divided randomly again into gentamicin group, etimicin group, ciprofloxacin group,fleroxacin group, cefuroxime group and cephradine group, with 20 mice in each group.INTERVENTIONS: C57BL/6 mice were immunized with the acetylcholine receptor(AChR) protein in complete Fruend' s adjuvant(CFA) to establish experimental autoimmune myasthenia gravis(EAMG) . Mice in saline group were injected normal saline and mice in antibiotics group were injected antibiotics(10 mg/kg), lasted 14 days. Mice in MG group were without any treatments. On the 7th day after the last immunization and the 14th day after the antibiotics treatments, MG scores was evaluated, repetitive nerve stimulation(RNS) and the levels of acetylcholine receptor antibody(AChRab)were tested at the same time.RESULTS; The mean symptom scores on the 14th day after the antibiotics treatment with gentamicin, etimicin, ciprofloxacin and fleroxacin were higher than that in MG group, and there was no significant difference in the mean symptom scores among cefuroxime group, cephradine group and MG group. The decrement percent of RNS in gentamicin group [ (21.22 ± 4.63)% ], etimicin group[ (19.08 ±4. 25)% ], ciprofloxacin group[ (22.25 ±4.95)% ] and fleroxacin group[ (21.71 ±4.99)% ] were higher than that in MG group[(15.75 ±2.22)% ], but no difference was found in the attenuation rate among cefuroxime group[(15.25 ±2. 87)% ],cephradine group[ ( 15.25 ± 3.30)% ] and MG group. The levels of AChRab in gentamicin, etimicin, ciprofloxacin and fleroxacin groups were also higher than that in MG group, but no difference was found among cefuroxime group, cephradine group and MG group.CONCLUSOIN: Aminoglycoside and fluoroquinolone antibiotics can aggravate the obstruction of NMJ transmission, and cephalosporin antibiotics have no obvious effect on the obstruction of NMJ transmission function in MG.
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In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24 h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.
Subject(s)
Animals , Rats , Apoptosis , Brain Ischemia , Metabolism , Calcium Channel Blockers , Pharmacology , Nimodipine , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Genetics , RNA, Messenger , Genetics , Rats, Wistar , bcl-2-Associated X Protein , GeneticsABSTRACT
To explore the relationship between beta-amyloid (A beta) and the pathogenesis of Alzheimer disease (AD), after injection of beta-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of A beta was also analyzed. A beta peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P < 0.05 or P < 0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of A beta (P < 0.05 or P < 0.01). It is concluded that A beta may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
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Acetylcholine/metabolism , Aging , Alzheimer Disease/etiology , Amyloid beta-Peptides/toxicity , Apoptosis/drug effects , Dexamethasone/pharmacology , Drug Synergism , Hippocampus/metabolism , Hippocampus/pathology , Injections, Intraventricular , Neurons/pathology , Rats, WistarABSTRACT
To investigate the effects of time interval and cumulative dosage of repetitive mild cellular hypoxia on shape of neurodegeneration and neuroprotection in mice, population spike amplitude (PSA) was measured during hypoxia and posthypoxic recovery in hippocampal slices from untreated control and mice pretreated in vivo with a single or repeatedly intraperitoneal injection of 3-nitropropionate (3-NP). Posthypoxic recovery of PSA was dose-dependent in single pretreated slices, with maximal recovery on pretreatment attained with 20 mg/kg 3-NP (82 +/- 32%, P < 0.01). Upon 5 and 9 treatments with 20 mg/kg 3-NP (dosage interval 3 days), PSA recovered to (38 +/- 9)% with the difference being not significant vs control group and (72 +/- 45)% with the difference being significant (P < 0.05 to control, P < 0.05 to 5 treatments), respectively. In contrast, with 2 days time interval, recovery after 5 and 9 treatments was (30 +/- 25)% and (16 +/- 14)%, respectively (without significant difference from control). Continued neuroprotection was also observed upon increase of dosage interval to 4 and 5 days. It was suggested that repetitive chemical hypoxia is a model for neurodegenerative disease and continued neuroprotection depending on time interval between repetitive hypoxic episodes rather than cumulative dosage. At appropriate time intervals increased neuronal hypoxic tolerance could be induced with number of hypoxic episodes.
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Animals , Male , Mice , Adaptation, Physiological , Cell Hypoxia , Disease Models, Animal , Hippocampus , Cell Biology , Huntington Disease , Ischemic Preconditioning , Neuronal Plasticity , Physiology , Nitro Compounds , Propionates , Time FactorsABSTRACT
To explore the relationship between beta-amyloid (A beta) and the pathogenesis of Alzheimer disease (AD), after injection of beta-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of A beta was also analyzed. A beta peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P < 0.05 or P < 0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of A beta (P < 0.05 or P < 0.01). It is concluded that A beta may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
Subject(s)
Animals , Male , Rats , Acetylcholine , Metabolism , Aging , Alzheimer Disease , Amyloid beta-Peptides , Toxicity , Apoptosis , Dexamethasone , Pharmacology , Drug Synergism , Hippocampus , Metabolism , Pathology , Injections, Intraventricular , Neurons , Pathology , Rats, WistarABSTRACT
Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-α (1-250 U/ml) or IL-1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-α (100 U/ml) or IL-1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-α, IL-1β in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.
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Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-α (1-250 U/ml) or IL-1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-α (100 U/ml) or IL-1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-α, IL-1β in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.
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Objective To explore Bcl-2 and Bax gene expression in hippocampus region after cerebral ischemia in rats and the modulation of expression by Nimodipine.Methods The cerebral ischemic model of rat was made by occluding left middle cerebral artery according to Nagasawy and Zea Longa improvement method. The rats in one group were pre-treated with Nimodipine. The expression of Bcl-2 and Bax mRNA were measured by RT-PCR method.Results Both Bcl-2 and Bax mRNA were induced in the hippocampus regions after middle cerebral artery occlusion. The Bcl-2 mRNA level was continuously high. However,the level of Bax mRNA increased gradually at first,reached a peak at 24 h,then decreased slowly.For the rats pretreated with Nimodipine Bcl-2 mRNA was up-regulated and Bax mRNA was down-regulated in the hippocampus at 6 and 24 h after ischemia.Conclusion Calcium antagonist can regulate Bcl-2 and Bax genes expression in the hippocampus region after cerebral ischemia.This study indicates that pharmacological modulation of Bcl-2 family member expression may become a new strategy to interfere with neuronal damage.