1.Research progress of Claudin family proteins in inflammatory bowel disease and colitis associated colorectal cancer
Practical Oncology Journal 2024;38(3):207-212
In recent years,the generation,maintenance and regulation of the intestinal mucosal barrier have become a re-search focus in the occurrence,development,treatment,and prognosis of inflammatory bowel disease(IBD)and colitis associated color-ectal cancer(CAC).Tight junction(TJ)proteins are an important component of the intestinal mucosal barrier,which the Claudin fami-ly proteins have become a research hotspot.This review mainly introduces the changes of Claudin protein in IBD and CAC,as well as the latest research progress on its role in the occurrence,development and clinical treatment of IBD and CAC.
2.Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases
Wei XIAO ; Longyi DU ; Linli CAI ; Tiwei MIAO ; Bing MAO ; Fuqiang WEN ; Gerard Peter GIBSON ; Deying GONG ; Yan ZENG ; Mei KANG ; Xinmiao DU ; Junyan QU ; Yan WANG ; Xuemei LIU ; Ruizhi FENG ; Juanjuan FU
Chinese Medical Journal 2022;135(13):1545-1554
Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.
3. Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor
Wenze WAN ; Peng ZHANG ; Xiangyu ZENG ; Hong ZHOU ; Yao LIN ; Zhen XIONG ; Ruizhi ZHANG ; Weizhen LIU ; Yong HAN ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(9):848-855
Objective:
To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 μg/L influences the efficacy of adjuvant therapy.
Methods:
A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis.
Results:
Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration <1100 μg/L and 53 patients with plasma concentration ≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all
4.Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor
Wenze WAN ; Peng ZHANG ; Xiangyu ZENG ; Hong ZHOU ; Yao LIN ; Zhen XIONG ; Ruizhi ZHANG ; Weizhen LIU ; Yong HAN ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(9):848-855
Objective To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration<1100 μg/L influences the efficacy of adjuvant therapy. Methods A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease?Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22?26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography?tandem mass spectrometry (HPLC?MS/MS). Patients were divided into<1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non?normal distribution were analyzed by Spearman correlation. Kaplan?Meier survival curves and COX regression model were used for survival analysis. Results Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c?Kit exon 11 mutation, 4 with c?Kit exon 9 mutation, 1 with c?Kit exon 11 and 17 mutation and 2 without c?Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration<1100 μg/L and 53 patients with plasma concentration≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow?up time was 30 (range 4?49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c?Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c?Kit exon 9 mutation. The 3?year relapse?free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration≥1100 μg/L. No significant difference in relapse?free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration<1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022?2.637, P=0.242). Conclusions IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.
5.Analysis of imatinib trough concentration at steady state in adjuvant therapy of patients with high risk gastrointestinal stromal tumor
Wenze WAN ; Peng ZHANG ; Xiangyu ZENG ; Hong ZHOU ; Yao LIN ; Zhen XIONG ; Ruizhi ZHANG ; Weizhen LIU ; Yong HAN ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(9):848-855
Objective To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration<1100 μg/L influences the efficacy of adjuvant therapy. Methods A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease?Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22?26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography?tandem mass spectrometry (HPLC?MS/MS). Patients were divided into<1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non?normal distribution were analyzed by Spearman correlation. Kaplan?Meier survival curves and COX regression model were used for survival analysis. Results Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c?Kit exon 11 mutation, 4 with c?Kit exon 9 mutation, 1 with c?Kit exon 11 and 17 mutation and 2 without c?Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration<1100 μg/L and 53 patients with plasma concentration≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow?up time was 30 (range 4?49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c?Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c?Kit exon 9 mutation. The 3?year relapse?free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration≥1100 μg/L. No significant difference in relapse?free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration<1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022?2.637, P=0.242). Conclusions IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.
6.Analysis of diagnosis and treatment of gastrointestinal stromal tumor recurrence and metastasis after postoperative adjuvant imatinib treatment
Wenze WAN ; Ruizhi ZHANG ; Chengguo LI ; Wenchang YANG ; Tao WANG ; Xiangyu ZENG ; Ming CAI ; Guobin WANG ; Peng ZHANG ; Kaixiong TAO
Journal of International Oncology 2018;45(11):665-669
Objective To investigate the clinical characteristics,treatment strategies and curative effect of recurrence and metastasis of primary gastrointestinal stromal tumor (GIST) after complete resection along with adjuvant therapy with imatinib,and to analyze the risk factors of recurrence and metastasis after adjuvant therapy.Methods The demographic data,clinicopathological characteristics and follow-up data of 80 primary GIST patients who received adjuvant therapy with imatinib for at least 1-year duration and had already stopped taking imatinib from January 2005 to December 2017 in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology were analyzed retrospectively.The survival analysis was performed using Kaplan-Meier approach.Univariate analysis was conducted using log-rank test.Multivariate analysis was produced by Cox regression model.Results Of the enrolled 80 patients,recurrence and metastasis were detected in 17 cases after completion of postoperative adjuvant therapy with imatinib,with a median recurrence time of 12 months.All the 17 patients showed no specific clinical manifestations.Liver metastasis,peritoneum metastasis and local recurrence were found in 9,5 and 3 cases,respectively.In the 17 patients with recurrence and metastasis,9 patients received imatinib monotherapy.Among the 9 patients,6 achieved partial responses,while 3 demonstrated stable disease,and secondary drug resistance was found in 7 patients during the follow-up period,with a median progression-free survival of 35 months (95% CI:15-55 months) and median overall survival of 49 months (95% CI:30-68 months).A total of 7 patients with recurrence and metastasis were treated with imatinib after operation and achieved satisfying tumor control,and secondary drug resistance was found in 4 patients during the follow-up period,with a median progression-free survival of 31 months (95% CI:6-56 months) and fell short of median overall survival.The remaining 1 patient gave up treatment.Univariate analysis showed that tumor location (x2 =4.120,P =0.042),preoperative neutrophil-to-lymphocyte ratio (NLR) (x2 =7.513,P =0.006) and preoperative platelet-to-lymphocyte ratio (PLR) (x2 =6.575,P =0.010) were associated with recurrence and metastasis of GIST patients after completion of adjuvant therapy.Multivariate analysis revealed that tumor location (HR =3.787,95% CI:1.126-12.732,x2 =4.631,P =0.031) was an independent prognostic factor for those patients.Conclusion GIST patients who are identified recurrence and metastasis after completion of adjuvant imatinib treatment show no specific clinical manifestations after stopping andjuvant therapy with imatinib.Compared with gastric GIST,non-gastric origin GIST has a higher risk of recurrence.Imatinib monotherapy and surgery combined with imatinib therapy are both effective in treating this subgroup of patients.
7.Causes and management for male urethral stricture
Caifang CHEN ; Mingqiang ZENG ; Ruizhi XUE ; Guilin WANG ; Zhiyong GAO ; Wuxiong YUAN ; Zhengyan TANG
Journal of Central South University(Medical Sciences) 2018;43(5):520-527
Objective:To explore the etiology of male urethral stricture,analyze the therapeutic strategies of urethral stricture,and summarize the complicated cases.Methods:The data of 183 patients with urethral stricture were retrospectively analyzed,including etiology,obstruction site,stricture length,therapeutic strategy,and related complications.Results:The mean age was 49.7 years,the average course was 64.7 months,and the constituent ratio of51 to 65 years old patients was 38.8% (71/183).The traumatic injury of patients accounted for 52.4% (96/183),in which the pelvic fracture accounted for 35.5% (65/183) and the straddle injury accounted for 16.9% (31/183).There were 54 cases of iatrogenic injury (29.5%).The posterior urethral stricture accounted for 45.9% (84/183),followed by the anterior urethral stricture (44.8%,82/183) and the stenosis (6.6%,12/183).A total of 99 patients (54.1%) received the end to end anastomosis,and 40 (21.9%) were treated with intracavitary surgery,such as endoscopic holmium laser,cold knife incision,endoscopic electroknife scar removal,balloon dilation,and urethral dilation.In the patients over 65-years old,the urethral stricture rate was 14.8% and the complication rate (70.4%) for transurethral resection of the prostate (TURP) was significantly higher than that of all samples (P< 0.01).Conclusion:Both the etiology of male urethral stricture and the treatment strategy have changed and the incidence of traumatic and iatrogenic urethral stricture has increased in recent 3 years.The main treatment of urethral stricture has been transformed from endoscopic surgery into urethroplasty.
8.Clinical efficacy and safety analysis of domestic imatinib for treatment of gastrointestinal stromal tumor
Peng ZHANG ; Wenze WAN ; Ruizhi ZHANG ; Xiangyu ZENG ; Zhen XIONG ; Ming CAI ; Xiaoming SHUAI ; Kailin CAI ; Jinbo GAO ; Guobin WANG ; Kaixiong TAO
Cancer Research and Clinic 2018;30(10):660-664
Objective To investigate the clinical efficacy and safety of domestic imatinib in the treatment of gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of GIST patients who received domestic imatinib treatment from January 2014 to December 2017 in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were analyzed retrospectively. The treatment efficacy and adverse reactions were analyzed. Results A total of 35 patients included 20 males and 15 females with a median age of 53 years old (28-79 years old). Among all the patients, 25 with primary GIST underwent complete resection, in which 20 cases were classified as high risk and 5 as moderate risk according to the risk stratification. Of the remaining 10 recurrent/metastatic or unresectable GIST patients, 6 cases had metastasis in liver, 2 cases had metastasis in peritoneum, 1 case had extensive abdominal and pelvic metastasis, and the other 1 case was initially unresectable. The follow-up data of all the 35 patients were available, with a median follow-up time of 25 months (4-49 months). Twenty-five primary patients with complete resection received adjuvant therapy with a median time of 14 months (4-44 months). The median time of follow-up was 25 months (4-49 months), and none of the primary patients was detected with recurrence or metastasis of GIST. Meanwhile, of the 10 patients with recurrent/metastatic or unresectableGIST, the median time of medicine-taking was 24 months (3-49 months). Seven of 10 patients received imatinib monotherapy, including 5 cases of partial remission and 2 cases of stable disease. The other 3 patients with localized progression received complete resection along with imatinib therapy. All the 10 patients achieved durable clinical benefit. Twenty-seven patients (77.1%) experienced adverse events, and only 1 case (2.9 %) had grade 3 adverse events. Conclusion Domestic imatinib is effective and safe for patients who received adjuvant therapy after complete resection of primary GIST as well as those with recurrent/metastatic or unresectable GIST, but it remains to be further confirmed by large samples of prospective studies.
9.Effect of calcium channel blockers on primary cultured human urethra scar fibroblasts.
Mingqiang ZENG ; Junjie CHEN ; Liang HUANG ; Ruizhi XUE ; Xuyu XIANG ; Fanchang ZENG ; Guilin WANG ; Zhengyan TANG
Journal of Central South University(Medical Sciences) 2016;41(12):1317-1322
To investigate effects of verapamil on primary cultured human urethral scar fibroblasts (USFs) and to provide basis for protecting the formation of urethra scar.
Methods: The cell proliferation was evaluated with the cell counting kit (CCK)-8 method after USFs were incubated various verapamil concentrations (50, 100, 150, 200, or 250 μmol/L) or solvent for 12, 24, or 48 h. The protein level of matrix metalloproteinase (MMP) was evaluated with ELISA after cells were incubated with verapamil (100 μmol/L) or solvent (control cells) for 24 h.
Results: The proliferation of USFs was obviously suppressed after verapamil treatment, which was in a dose-dependent and time-dependent manner. Meanwhile, the protein levels of MMP-2 and MMP-9 in the verapamil treatment group increased obviously compared with those of the control groups (P<0.05).
Conclusion: Calcium channel blockers may prevent the excessive formation of urethra scar by inhibiting the proliferation of urethral scar fibroblasts and enhancing the activity of MMP.
Calcium Channel Blockers
;
pharmacology
;
Cell Proliferation
;
drug effects
;
Cells, Cultured
;
Cicatrix
;
prevention & control
;
Fibroblasts
;
drug effects
;
Humans
;
Matrix Metalloproteinase 2
;
drug effects
;
Matrix Metalloproteinase 9
;
drug effects
;
Matrix Metalloproteinase Inhibitors
;
pharmacology
;
Up-Regulation
;
drug effects
;
Urethra
;
cytology
;
pathology
;
Verapamil
;
pharmacology
10.A preliminary study on mechanisms for urinary system disorders before and after ketamine withdrawal in rats.
Mingqiang ZENG ; Liang HUANG ; Zhengyan TANG ; Yonglin LI ; Fanchang ZENG ; Ruizhi XUE
Journal of Central South University(Medical Sciences) 2015;40(3):269-275
OBJECTIVE:
To explore the mechanisms for urinary system disorders before and after ketamine withdrawal in rats and to evaluate the recovery degree of the urinary system damage after ketamine withdrawal.
METHODS:
Fifteen male healthy Sprague-Dawley rats were randomly divided into 3 groups: A control group, an experimental group, and a withdrawal group. The rats in the control group were given normal saline. The rats in the experimental group were given ketamine 30 mg/(kg.day) for 30 days. The rats in the withdrawal group were treated as the experimental group except for drug withdrawal for 2 weeks. In the experimental period, we randomly selected 1 rat of kidney, ureter, and bladder from each group to perform HE staining. The bladder tissues in each group were used to detect mRNA expression by quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS:
1) The behavior of ketamine-injected rats was obviously changed, but the weight of ketamine-induced rats was not changed. 2) As compared with the control group, the experimental and withdrawal groups showed infiltration of mononuclear inflammatory cells in the kidney tissues, the thinner epithelium of bladder and infiltration of submucosal mononuclear inflammatory cells under the optical microscope. 3) As compared with the control group, the expression of H1R mRNA was increased in the experimental group (P<0.05). As compared with the experimental group, H1R mRNA expression was significantly decreased in the withdrawal group (P<0.05).
CONCLUSION
Ketamine abuse could induce behavior changes in rats. The infiltration of mononuclear inflammatory cells in kidney and bladder, the thinner bladder epithelial layer, and the increased H1R gene mRNA expression in bladder might be an important pathogenesis of KAUD. Ketamine withdrawal may effectively reverse the pathogenic process of KAUD.
Animals
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Epithelium
;
physiopathology
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Ketamine
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administration & dosage
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Kidney
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physiopathology
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Male
;
RNA, Messenger
;
Rats
;
Rats, Sprague-Dawley
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Urinary Bladder
;
physiopathology
;
Urologic Diseases
;
physiopathology

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