1.Constructing muscle-relaxation rabbit models by continuous infusion of propofolin in the internal carotid artery:pharmacokinetic variations
Hong YIN ; Yuan TAN ; Zhiyin TANG ; Rongwu XIANG ; Junchao ZHU
Chinese Journal of Tissue Engineering Research 2015;(27):4394-4399
BACKGROUND:Intracerebral administration of selective drugsviathe carotid artery is currently one of the effective methods to enhance the drug concentration in the brain and reduce the influence of drugs on other system functions. OBJECTIVE:To establish the muscle-relaxation rabbit models by infusing propofol continuously in the internal carotid artery and analyze the variations of propofol concentration. METHODS: The muscle-relaxation rabbit models were established by continuously infusing propofol at a constant speedviacatheterization in the internal carotid artery. The pharmacokinetic characteristics could be analyzed by the methods of obtaining arterial and venous blood on both sides of neck and samples of brain tissue on both sides in different points, detecting drug concentration using high pressure liquid assay, and then mathematicaly conversing the resulting data for fitting processing and statistical regression. RESULTS AND CONCLUSION:The method of determining the concentration of propofol using high pressure liquid assay is feasible, stable and reliable. Through investigating the concentration of propofol infused via the carotid artery at different time points, we discovered that the growth rate distribution of propofol concentration and data distribution are in log-normal distribution profile which belong to non-exponential kinetics model,i.e., modified log-normal distribution model,??)(ln x μ 2 1 fx ()=e 2σ2 , whereσ is the range of drug concentration growth indicating stability xk 2πσ of concentration changes, which is an integrated variable related to various factors, such as brain tissue uptake of drugs and brain circulation. The pharmacokinetic model of continuously infusing propofol in the internal carotid artery belongs to log-normal distribution function, i.e., a non-exponential function kinetics model. The brain concentration variations on both sides changing over time folow log-normal distribution function law.
2.Uric acid stimulates rat glomerular mesangial cells proliferation via activation of extracellular signal-regulated kinases
Hong XIANG ; Songming HUANG ; Quancheng FENG ; Yanggang YUAN ; Aihua ZHANG
Chinese Journal of Nephrology 2010;26(12):892-897
Objective To explore the effect of uric acid (UA) on the rat glomerular mesangial cells (GMCs) and its possible mechanism in vitro. Methods Cultured rat GMCs were treated with various concentrations of UA (50 μmol/L, 100 μmol/L, 300 μmol/L) in the presence or absence of U0126, apocynin, rotenone. The incorporation of 3H-thymidine (3H-TdR) and cell counting were used to measure GMCs proliferation. GMCs cell-cycle was analyzed by flow cytometry. CyclinD1 and cyclin A2 expression were determined by real-time PCR and Western blotting analysis. ERK1/2 phosphorylation was detected by Western blotting. Reactive oxygen species (ROS) was measured by 2, 7-dichlorofluorescein diacetate (DCFDA) fluorescence. Results (1) Uric acid increased GMCs proliferation in dose-dependent manner compared with the control groups, as assessed by 3H-TdR incorporation and cell counting. GMCs proliferation induced by 300 μmol/L uric acid was increased by more than 1.5-fold assessed by both of the methods. (2) Uric acid decreased cell number in G1/G0 phase and increased cell number in S phase in dosedependent manner, as assessed by flow cytometry. (3) Uric acid iuduced cyclin D1 and cyclin A2 expression in dose-dependent manner. (4)Uric acid increased pospho-ERK1/2 in dose-dependent manner and ERK1/2 specific inhibitor U0126 could suppress uric acid-induced cell proliferation.The inhibition percentage of U0126 was 22% and 31% assassed by cell counting and 3H-TdR incorporation, respectively. (5) Uric acid increased ROS production in dose-dependent manner.NADPH oxidase inhibitor apocynin could also significantly inhibit uric acid-induced ROS production, ERK phosphorylation and cell proliferation. In contrast, rotenone had no effect on them.Conclusion Uric acid can stimulate rat GMCs proliferation, partially by the activation of ERK pathway via NADPH oxidase-derived ROS generation.
4.Effects of Leukotriene B4-Leukotriene B4 Receptor Pathway in Vascular Immunizing Damage of Kawasaki Disease
yuan-xiang, WEI ; hong-wei, WANG ; min, KANG
Journal of Applied Clinical Pediatrics 2004;0(09):-
Objective To investigate the role of serum in children with Kawasaki disease(KD)in acute stage and ?-globulin role in monocyte cell-produced leukotriene B4(LTB4).Meanwhile,to investigate the effects of the monocyte cell conditioned media(MCM)on the expression of leukotriene B4 receptor 2(BLT2)in endothelial.In order to understand whether LTB4-BLT2 pathway gets involved in vascular damage in KD and the mechanism of ?-globulin in the lessening vascular damage of KD.Methods The concentration of LTB4 in cell culture after the stimulation by serum of healthy children,serum of acute KD and serum of acute KD with ?-globulin were observed,respectively.The expression of BLT2 in the endothelial was determined by flow cytometry.Results 1.The serum of children with KD increased the concentration of LTB4 in MCM(P
5.Analysis of surveillance results of Keshan disease in Shandong Province in 2010
Xiu-hong, WANG ; Yuan-yuan, WANG ; Jing, WANG ; fu-rong, QU ; Yuan, LIU ; You-zhang, XIANG ; Wen-ming, ZHANG
Chinese Journal of Endemiology 2011;30(6):673-677
Objective To investigate the incidence of Keshan disease(KSD) in Shandong province and to supply evidence for scientific control of the disease.Methods According to the scheme of KSD monitoring in Shandong province,the KSD cases were searched in 7 counties,and representative 3 counties and 6 villages were selected as key monitoring sites.In each site,about 420 residents were checked by asking detailed disease history,physical examination,and electrocardiography (ECG) tracings.Suspected cardiac abnormalities were taken chest posteroanterior X-ray film.At the same time,residents hair and food samples were collected to detect selenium levels in internal and external environments,and residents' income and per capita share of grain and other basic information were collected.Results ①Two hundred and fifty-nine medical units were searched,1132 cases of myocardial disease were found out and 638 suspected cases were identified and 142 chronic KSD cases were diagnosed.②In the 6 monitoring sites,2538 residents were surveyed and 91 cases of KSD were detected(of which 77 cases of potential,14 cases of chronic),the detection rate was 3.58%.A total of 2127 residents were traced ECG and the incidence of abnormal ECG was 24.5% (521/2127),of which ST-T changes,T-wave changes,sinus bradycardia,sinus arrhymia,sinus tachycardia,and atrial premature beats et al were more common.Of the 75 X-ray films,39 cases had enlarged heart(in which 21 of mild,13 of moderate,5 of severe).③A total of 406 hair and grain samples were collected,respectively,and the selenium content of hair was approaching the level of appropriate,and the selenium content of food was still low.The annual per capita incomes of each site were between 3000 - 5900 Yuan,and residents main staple food was flour.Conclusions KSD in Shandong province is in a relatively stable situation.But latent and chronic KSD cases can still be detected.The internal environment selenium levels are elevated since the local living standards and dietary nutrition are improved.
6.Health management needs of 104 enterprises in Jingzhou city of Hubei province
Hong YUAN ; Lihua ZHANG ; Xuepeng ZHANG ; Yanping XIANG ; Jun LI ; Li DING ; Mingjun LU
Chinese Journal of Health Management 2010;04(6):337-339
Objective To understand enterprises' demands for health management. Methods Self-designed questionnaires were distributed to senior managing directors from 104 enterprises in Jingzhou City of Hubei Province. The counting data were expressed as percentage or accumulated percentage. Results The main health problems in Jingzhou City were chronic diseases (28.4%), unhealthy behaviors (40. 1% ), occupational diseases ( 22. 8% ), and enviromental pollution ( 8.7% ). Health service needs of enterprises included health speeches (37.2%),health consultation (53.8%),medical report interpretation (43. 2% ), nutrition intake guidance ( 10. 5% ), and green passage medical treatment ( 14. 7% ).Conclusion All the enterprises show strong needs for health management. Establishing appropriate health management model may have better prospects.
7.Effects of Fosinopril on Transforming Growth Factor-Beta 1 Secretion and mRNA Expression of Cultured Rats Glomerular Mesangial Cell
li-na, WANG ; zhi-hong, HAO ; zhi-yuan, WENG ; li, YU ; you-xiang, ZHANG
Journal of Applied Clinical Pediatrics 2006;0(13):-
Objective To observe the effects of fosinopril(FOS),a new generation angiotensin-converting enzyme inhibitor(ACEI),on protein and mRNA expression of transforming growth factor-?_1(TGF-?_1) of rat glomerular mesangial cell(GMC) induced by lipopolysaccharide(LPS);to demonstrate the preventive mechanism against glomerular sclerosis by applying FOS.Methods The cultured GMC in classic way were divided into 3 groups:control group;LPS group;LPS+FOS group.TGF-?_1 concentration in GMC supernatant fluid was detected by ELISA;TGF-?_1 mRNA expression was determined by semiquantitative real-time RT-PCR.Results LPS group was obviously higher than control groups in TGF-?_1 secretion and mRNA expression,while LPS+FOS group decreased distinctively in TGF-?_1 secretion and mRNA expression compared with LPS group.Conclusions FOS has obviously inhibited on TGF-?_1 expression of rat GMC both at protein level and mRNA level,which reveals that it may be an important mechanism by FOS on restraining the development of glomerulosclerosis.
8.Protective effects of intermedin preconditioning on hypoxic injury in rat's cardiac myocytes.
Qiu-xiang DU ; Yu-sheng QIN ; Jia LIU ; Jun-hong SUN ; Ying-yuan WANG
Journal of Forensic Medicine 2014;30(4):257-260
OBJECTIVE:
To observe the effects of intermedin preconditioning on hypoxic injury in rat's cardiac myocytes and to provide the hypothetical mechanism of sudden cardiac death in the field of forensic pathology.
METHODS:
The H9c2 cultured rat cardiac myocytes were randomly divided into control group, hypoxia group and IMD group. The myocardial cell viability, cellular ultrastructure, intracellular calcium concentration and apoptosis rate were determined by MTT assay, transmission electron microscopy, laser scanning confocal microscope and flow cytometry, respectively.
RESULTS:
Compared with the control group, cell viability obviously decreased with inner ultrastructure injury in the hypoxia group (P<0.05), while cell viability significantly increased in the IMD group by reducing the hypoxia injury of cardiac myocytes (P<0.05). Compared with the control group, [Ca2+]i (fluorescence intensity) and apoptosis rate significantly increased in the hypoxia group, but decreased in the IMD group (P<0.05).
CONCLUSION
IMD increases the cell survival rate and decreases the cell apoptosis inhibited by intracellular calcium overload from hypoxia. This finding may reveal the mechanism of protective effects of myocardial hypoxia, and provide a scientific basis for the identification sudden cardiac death.
Animals
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Apoptosis
;
Calcium
;
Cell Hypoxia
;
Cell Survival
;
Hypoxia
;
Myocardial Ischemia
;
Myocardium/cytology*
;
Myocytes, Cardiac/physiology*
;
Rats
;
Rats, Sprague-Dawley
9.Relation between Injury Time and the Expression of COX6C mRNA in Skeletal Muscle of Rats after Contusion.
Jun-hong SUN ; Lei ZHANG ; Xiao-wei WANG ; Qiu-xiang DU ; Jian LU ; Ying-yuan WANG
Journal of Forensic Medicine 2015;31(3):177-180
OBJECTIVE:
To investigate the relation between injury time and the expression of cytochrome c oxidase subunit VIc (COX6C) mRNA in skeletal muscle of rat after contusion.
METHODS:
A total of fifty-four SD rats were divided into the control group and the contusion groups (0.5, 1, 6, 12, 18, 24, 30, and 36 h after contusion), randomly. The contusion model was established by free fall drop of gravity hammer. At corresponding time point after contusion, the regular histology was examined and expression level of COX6C mRNA was tested by real-time PCR after extraction of total RNA from the tissues.
RESULTS:
The main pathological features of 6 h after injury included edema and hemorrhage in myocytes with no inflammatory cells found. After 6 hours, the findings included myocyte degeneration and necrosis, inflammatory cells infiltration, and fibrous connective tissue proliferation in the contused zone. The expression level of COX6C mRNA was higher than that of the control group within 6 h after contusion. The expression level was lower than that of the control group from 6-36 h after contusion.
CONCLUSION
The level of COX6C mRNA expresses in a regular way after contusion. It may be useful for estimating wound age in combination with the results of pathological features.
Animals
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Contusions/metabolism*
;
Electron Transport Complex IV/metabolism*
;
Muscle, Skeletal/metabolism*
;
RNA
;
RNA, Messenger
;
Rats
;
Rats, Sprague-Dawley
;
Real-Time Polymerase Chain Reaction
;
Time Factors
10.Effect of aldosterone and its antagonist spironolactone on epithelial-mesenchymal transition of mormal rat kidney epithelial cells in high glucose
Kanghan LIU ; Qiaoling ZHOU ; Xiang AO ; Pouranan VEERARAGOO ; Xuemin HONG ; Zhou XIAO ; Mingxia YUAN
Journal of Central South University(Medical Sciences) 2010;35(3):222-229
Objective To determine the effect of aldosterone and its antagonist, spironolactone on epithelial-mesenchymal transition (EMT) of normal rat kidney epithelial cells (NRK-52E) in a high glucose milieu,and to explore the mechanism of renoprotection in diabetic nephropathy (DN ) in rats involving aldosterone and spironolacton. Methods NRK-52E cells were simultaneously cultured in the serum-free Dulbecco's modification of Eagle's medium Dulbecco (DMEM) for 12 hours. Then the low glucose (LG) group was cultured in LG (1000 mg/L) DMEM:The high glucose (HG) group was cultured in high glucose (4 500 mg/L) DMEM. The aldosterone (Aldo) groups were cultured in high glucose DMEM with the addition of 10,50 and 100 nmol/L aldosterone respectively. The SP group was cultured in high glucose (4 500 mg/L) DMEM plus 10~(-7)mol/L spironolactone. Immunohistochemistry, RT-PCR and Western blot were used to detect E-cadherin and α smooth muscle actin(α-SMA) mRNA expression. Results RT-PCR showed that compared with the LG Group, E-cadherin mRNA expression in the HG group was significantly lower, and α-SMA mRNA expression was significantly increased(P<0.05). E-cadherin mRNA expression in the 50 nmol/L Aldo group and 100 nmol/L Aldo group was significantly lower than that in the HG group, while the expression of α-SMA mRNA was significantly increased in the HG group(P<0.05), with a dose-dependent relationship with aldosterone(r=-0.70,P<0.05;r=0.67, P<0.05). E-cadherin mRNA in the SP group was significantly higher,while α-SMA mRNA expression was lower than that in the HG group(P<0.01). Immunohistochemistry and Western blot showed that compared with the LG group, E-cadherin protein expression was significantly reduced, and α-SMA expression was significantly increased in the HG group(P<0.01). In the 10 nmol/L Aldo, 50 nmol/L Aldo, and the 100 nmol/L Aldo groups, E-cadherin protein expression was significantly lower, and α-SMA protein expression was significantly higher than that in the HG group(P<0.05), with a dose-dependent relationship with aldosterone(r=-0.83,P<0.05;r=0.81, P<0.05). In the SP group, E-cadherin protein expression was higher, and α-SMA protein level was lower than that in the HG group(P<0.05). Conclusion Aldosterone can promote EMT of tubular epithelial cells in a high sugar milieu, leading to renal interstitial fibrosis in Diabetic nephropathy. Spironolactone can inhibit high glucose-induced renal tubular epithelial cells EMT, which may be an important mechanism for the inhibition of renal interstitial fibrosis.