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Objective:To investigate the early curative effects of robot-assisted total knee arthroplasty (TKA) in the treatment of valgus knee.Methods:A retrospective study was conducted to analyze the data of 40 patients with valgus knee who had been treated by TKA at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from January to December 2021. The patients were divided into 2 groups according to whether a robot had been used or not for TKA. In the observation group of 15 cases for which TKA was assisted by a robot, there were 4 males and 11 females with an age of (65.5±6.2) years, and the disease course was 42 (36, 54) months; in the control group of 25 cases for which conventional TKA was performed, there were 8 males and 17 females with an age of (65.8±7.5) years, and the disease course was 42 (36, 60) months. Surgical time, hemoglobin decrease, and knee joint range of motion, American Knee Society Score (KSS), hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) at 12 months after surgery were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The surgical time in the observation group was (148.0±21.2) min, significantly longer than that in the control group [(115.2±7.1) min], and the hemoglobin decreased by (11.8±1.1) g/L in the observation group, significantly less than that in the control group [(18.1±1.8) g/L] ( P<0.05). The observation group and the control group were followed up for 13 (13, 14) and 13 (13, 14) months after surgery, respectively, showing no statistically significant difference ( P>0.05). At 12 months after surgery, the KSS knee score, KSS functional score, and knee range of motion in the observation group were (86.1±4.6) points, (86.9±3.1) points, and 115.7°±5.0°, significantly larger than those in the control group [(82.2±3.5) points, (82.8±0.9) points, and 108.2°±5.0°] ( P<0.05). Reexamination of full-length radiographs of both lower limbs in all patients showed good positions of the prostheses and no such adverse events as loosening or sinking at 12 months after surgery. The HKA (178.5°±1.2°) and LDFA (89.1°±0.7°) at 12 months after surgery in the observation group were significantly larger than those in the control group (176.6°±1.5°, 88.2°±8.2°) ( P<0.05); there was no statistically significant difference in MPTA between the 2 groups ( P>0.05). Conclusions:In the treatment of valgus knee, robot-assisted TKA can correct joint deformity, and achieve precise osteotomy and functional alignment of lower limbs, leading to better early curative effects than conventional TKA.
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OBJECTIVE@#To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.@*METHODS@#Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.@*RESULTS@#The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.@*CONCLUSION@#Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
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Animals , Humans , Mice , Apoptosis , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Signal TransductionABSTRACT
OBJECTIVE@#To investigate the therapeutic effect of moxibustion on sarcomas from mesenchymal tissues, which have a low response rate to chemotherapy and radiotherapy.@*METHODS@#S180 sarcoma cell line was inoculated in C57BL/6 mice to form transplanted tumor. Moxibustion therapy was directly applied at the transplanted tumor sites, at a distance of 3.0 cm, 10 min per session, till skin temperature reached 45 °C, once a day, for 14 consecutive days of intervention. After the mice were killed, serum was collected and used to detect concentrations of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), IL-4 and interferon-γ (IFN-γ) by Luminex liquid suspension chip. The numbers of Treg@*RESULTS@#Weight of S180 transplanted tumor in the control group was (2.03 ± 0.54) g, and that in the moxibustion group was (1.27 ± 0.29) g, which was statistically different (P = 0.023). The mean value of Foxp3@*CONCLUSION@#Moxibustion may have therapeutic effects on sarcomas by reducing the number of Treg cells in the blood and controlling the infiltration of Treg cells in the TME.
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Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.
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As a glycopeptide antibiotic,vancomycin is the first choice for treatment of methicilin-resistant staphylococcus aureus (MRSA) infection.Because of the metabolic individual difference,if children were given the dose according to the instruction,few patients can achieve the valley concentration as recommended in the guideline.So it's necessary for optimizing individual vancomycin dosage regimen with the help of therapeutic drug monitoring (TDM) and population pharmacokinetics model-nonlinear mixed effect model (NONMEM),in order to realiz the combination of effect and safety.This article will introduce the population pharmacokinetics model of vancomycin in children and discuss about major parameters influencing vancomycin metabolism,including age,body mass index,renal function,health condition,and drug combination.With rational therapeutic drug monitoring and optimizing parameters of NONMEM,we hope to realize area under concentration-time curve/minimum inhibit concentration (AUC/MIC) ratio ≥400,and to provide the reference for safe and rational pediatric dosage regimen.
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Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods: The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results: MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions: These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
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OBJECTIVE@#To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism.@*METHODS@#The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot.@*RESULTS@#MTT assay indicated bortezomib (2.5 μM, 5 μM, 10 μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9.@*CONCLUSIONS@#These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
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Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results:MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
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<p><b>OBJECTIVE</b>To investigate the effects of the furin inhibitor α1-PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms.</p><p><b>METHODS</b>The changes in the growth, migration and invasion of α1-PDX-transfected HeLa cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. HeLa cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded.</p><p><b>RESULTS</b>Compared with the control cells, α1-PDX-treated cells showed a significant growth inhibition by 18.4% at 24 h (P<0.01) with obviously lowered migration ability and cell invasiveness (P<0.01). Treatment with α1-PDX significantly reduced furin enzyme activity and MTI-MMP protein levels in HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors.</p><p><b>CONCLUSION</b>α1-PDX can inhibit the growth, metastasis and tumorigenicity of HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.</p>
Subject(s)
Animals , Female , Humans , Mice , Furin , HeLa Cells , Mice, Nude , Neoplasm Transplantation , Transfection , Uterine Cervical Neoplasms , Pathology , alpha 1-Antitrypsin , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To determine the minimum alveolar concentration (EC(50) and EC(95)) of sevoflurane in body movement response to surgical incision during combined anesthesia with dexmedetomidine, sevoflurane and fentanyl.</p><p><b>METHODS</b>Twenty-six ASA class I or II patients (aged 18-60 years) underwent selective surgery for lumbar disc herniation under general anesthesia with the combination of with dexmedetomidine, sevoflurane and fentanyl. All the patients received infusion with 0.5 mg/kg dexmedetomidine for 10 min before anesthesia induction with intravenous injection of 3 µg/kg fentanyl 8% sevoflurane inhalation. Upon loss of consciousness, sevoflurane concentration was reduced to 5% with intravenous injection of 1-2 mg/kg succinylcholine, and intubation was started after muscles relaxation. Anesthesia was maintained by sevoflurane and dexmedetomidine (0.2 µg·kg(-1)·h(-1)). Before the surgery, a steady state end-tidal sevoflurane concentration was maintained for at least 10 min. The first patient of the series was tested with 1.5% sevoflurane, and the concentration was adjusted according to modified Dixons up-and-down method (with a step size of 0.2%). Probit analysis was used for calculating EC(50), EC(95) and the 95% confidence interval (CI).</p><p><b>RESULTS</b>The EC(50) of sevoflurane was 0.94% (95%CI of 0.76%-1.07% ) and EC(95) was 1.23% (95%CI 1.09%-2.05% ).</p><p><b>CONCLUSION</b>The EC(50) and EC(95) of sevoflurane are 0.94% and 1.23%, respectively, for suppressing body movement in response to surgical incision during combined anesthesia with sevoflurane, dexmedetomidine and fentanyl.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Anesthesia , Methods , Anesthetics , Dexmedetomidine , Fentanyl , Methyl Ethers , Pharmacokinetics , Pulmonary Alveoli , Metabolism , Reference ValuesABSTRACT
<p><b>BACKGROUND</b>The goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons.</p><p><b>METHODS</b>From January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients.</p><p><b>RESULTS</b>Totally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation.</p><p><b>CONCLUSIONS</b>Awake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Anesthesia , Methods , Brain Mapping , Methods , Brain Neoplasms , Diagnostic Imaging , General Surgery , Deep Brain Stimulation , Methods , Neoplasms, Neuroepithelial , Diagnostic Imaging , General Surgery , UltrasonographyABSTRACT
Objective To investigate the feasibility of NR2B small interference RNA(NR2B siRNA)carried by water-soluble lipopolymer(WSLP)for treatment of neuropathic pain in rats.Methods One hundred healthy male SD rats weighing 180-200 g were randomly divided into 5 groups(n=20 each):normal control group (group C),sham operation group(group S),neuropathic pain group(group NP),group WSLP-NR2B siRNA (group W)and group WSLP-negative NR2B siRNA(group WN).Neuropathic pain was induced by partial ligation of sciatic nenre.WSLP-NR2B siRNA complex was formed by binding WSLP and NR2B siRNA.Normal saline.WSLP-NR2B siRNA complex and WSLP-negative NR2B siRNA 20μl were injected intrathecally after operation in NP,W and WN groups respectively.Mechanical withdrawal threshold(MWT)and thermal withdrawal duration (TWD)were measured before(baseline)and at 3,7,14 and 21 days after operation.Ten animals in each group were sacrificed on the 3rd day after operation and the lumbar segment(L4-6)of the dorsal root ganglia was removed for determination of the expression of NR2B mRNA and protein using RT-PCR and Western blot analysis.Results Sciatic nerve ligation significantly decreased MWT and prolonged TWD and increased NR2B mRNA and protein expression in group NP as compared with group C.WSLP-NR2B siRNA complex significantly reduced sciatic nerve ligation-induced hyperalgesia and decreased NR2B mRNA and protein expression in group W as compared with group NP.Conclusion WSLP not only mediates NR2B siRNA successfully and inhibits the expression of NR2B,but also reduces neuropathic pain in rats.
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Objective To compare diagnostic value of ~(18)F-fluoredeoxyglucose (FDG) PET/CT with contrast-enhanced CT in detecting primary hepatic carcinoma and postoperative recurrence.Methods Twenty-five cases of primary hepatic carcinoma or postoperative recurrent tumor underwent whole-body ~(18)F-FDG PET/CT and contrast-enhanced CT within one week's interval.They were retrospectively reviewed and the difierences between these two modalities were investigated.Results Of these 25 cases,there were 13 cases with primary hepatocellular carcinoma.1 case with intrahepatic cholangiocarcinoma and 11 cases with postoperative recurrence.The sensitivity of 18 F-FDG PET/CT and contrast-enhanced CT in diagnosing primary hepatic carcinoma was 78.6%(11/14) and 92.9%(13/14),and sensitivity in diagnosing postoperative recurrent was 100.0%(11/11) and 63.6%(7/11) respectively.Conclusion Contrast-enhanced CT may have a slight advantage over PET/CT in detecting primary hepatic carcinoma,but ~(18)F-FDG PET/CT combined with contrast-enhanced CT has even greater accuracy.Meanwhile,~(18)F-FDG PET/CT has better diagnostic accuracy in detection of postoperative recurrent tumor.
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<p><b>OBJECTIVE</b>To develop a portable field anesthesia machine system suitable for the medical first-aid on the spot.</p><p><b>METHODS</b>The three-dimensional structure of PFAM was designed with modeling software of Pro/E and manufactured according to the GB9706.29 and other national standards.</p><p><b>RESULT</b>Due to its small footprint and very light weight, PFAM is completely portable and convenient on different occasions within or outside a hospital environment. It can support breathing of patients and delivery anesthetic gas, fitted for both adult and children patients. All of the safety alarm systems required are employed on board.</p><p><b>CONCLUSION</b>PFAM may play an important role in the first-aid in the field or outside the hospital.</p>
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Anesthesiology , Equipment Design , Military Medicine , Monitoring, Ambulatory , SoftwareABSTRACT
Objective To compare bispectral index (BIS) with narcotrend index (NI) during propofol-remifentanil anesthesia administered by target-controlled infusion (TCI).Methods Ten ASA Ⅰ or Ⅱ pafients aged 18-56 yr weighing 52-67kg undergoing abdominal surgery lasting>1h were included in this study.BIS and NI were monitored simultaneously.Anesthesia was induced with TCI of propofol with target plasma concentration (Cp) of 3～4μg/ml and remifentanil (Cp 3-4ng/ml).Tracheal intubation was facilitated with cis-atracurium 0.3 mg/kg.The patients were mechanically ventilated.PETCO2 was maintained between 30-35 mm Hg.Anesthesia was maintained with TCI of propofol and remifentanil by the anesthesiologist bhnded to BIS and NI values.according to hemedynamic parameters.BIS and narcotrend values were recorded every minute and compared by another anesthesiologist.All data were compared by Bland-Altman analysis and with Kappa coefficient for agreement.The correlation between BIS and NI was tested by Spearman correlation analysis.The number of error ofjudgement (Type Ⅰ was defined as BIS<40 and NI>62;Type Ⅱ was defined as BIS>60 and NI<20)Was counted.Results The correlation and agreement between BIS and NI during maintenance of propofol-remifentanil anesthesia administered by TCI showed good consistency.Conclusion Both NI and BIS Can help anesthesiologist control the depth of anesthesia during TCI of propofol-remifentanil.
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Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia.
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<p><b>OBJECTIVE</b>To investigate the effect of phosphorylated-ERK1/2 (p-ERK1/2) on inducible nitric oxide synthase (iNOS) expression in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD), and explore the possible mechanism of dopaminergic (DA) neuron loss in the SN of the midbrain in PD.</p><p><b>METHODS</b>PD was induced by intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) in C57BL/6N mice, and the behavioral changes of the PD mouse model were observed. Immunohistochemistry and Western blotting were used to detect the number of positive cells and the expressions of tyrosine hydroxylase (TH), p-ERK1/2 and iNOS in the SN of the PD mice, and their changes following Rg1 treatment were assessed.</p><p><b>RESULTS</b>The PD mice exhibited typical symptoms of PD, in which the number of TH-positive neurons and TH expression were significantly reduced by about 77% and 75% (P<0.01), respectively, 7 days after the 5th injection of MPTP as compared with those in the control group. Rg1 pretreatment significantly decreased the number of TH-positive neurons and TH expression by 44% and 41% (P<0.01), respectively. p-ERK1/2 expression was not observed in the cell nuclei until 1.5 h after the third injection of MPTP, and increased markedly at 6 h. Rg1 pretreatment significantly inhibited the expression of p-ERK1/2 and iNOS (P<0.01). A significant positive correlation was noted between the expression of p-ERK1/2 and iNOS (P<0.01).</p><p><b>CONCLUSION</b>P-ERK1/2 may regulate the expression of iNOS to induce DA neuron loss in the SN of PD, and Rg1 may protect the DA neurons possibly by depressing nuclear translocation of P-ERK1/2.</p>
Subject(s)
Animals , Male , Mice , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Extracellular Signal-Regulated MAP Kinases , Chemistry , Pharmacology , Ginsenosides , Pharmacology , Mice, Inbred C57BL , Nitric Oxide Synthase Type II , Genetics , Metabolism , Parkinson Disease, Secondary , Phosphorylation , Substantia NigraABSTRACT
BACKGROUND: Cervical sympathetic ganglia block accelerates the re covery of the homeostasis of organic nervous-endocrine-immune system, butit is still unclear whether it can suppress the imbalance of homeostasis in duced by post-traumatic stress disorder. OBJECTIVE: To observe the effect of cervical sympathetic ganglia blockon the mortality of mice with combined radiation and burn injury, andwhether it can become an easy and effective method to treat secondarydamage after serious trauma. DESIGN: A randomized grouping design, an animal controlled experiment. SETTING: Department of Anesthesiology, Guangzhou General Hospital, Guangzhou Military Area Command of Chinese PLA.MATERIALS: The experiments were carried out in the Institute of Combined Injury, the Third Military Medical University of Chinese PLA between February 2004 and July 2005. Totally 160 Kunming mice were randomly divided into control group (n=50) and cervical sympathetic ganglia block group (n=50). In the control group, the mice were only induced to models of combined radiation and bum injury, and treated with injection of 0.3 mL saline at cervical part. In the cervical sympathetic ganglia block group, the mice were induced to models of combined radiation and burn injury, and then treated with cervical sympathetic ganglia block, once a day for 14 days continuously.METHODS: Methods to induce injury in the animals: ① Radiation injury: The mice were given even radiation of 60Coγ ray (5 Gy) at a distance of 1.5 m to the whole body, the rate of absorptive dosage was (5.17-5.33) mGy/s. ② Burn injury: After the radiation injury, coagulated gasoline was smeared on the back and burnt for 8 s to induce degree Ⅲ burn injury of 15% of the total body surface, which was proved by the pathological section. Methods of cervical sympathetic ganglia block: Cervical sympathetic ganglia block was given bilaterally, and then the mice were injected with 0.2 mL lidocaine (5 g/L), and it was observed whether the symptoms similar to Horner syndrome (hyperemia of conjunctiva, drooping eyelid,blushing, smaller eyeslit) occurred or not at 5 minutes after injection.MAIN OUTCOME MEASURES: The mortality at 2, 5, 7, 10, 20 and30 days after injury and the changes of the numbers of red blood cells,white blood cells and blood platelet in peripheral blood at 7, 14 and 21 days after injury were observed in both groups. The effects of cervical sympathetic ganglia block on the levels of tumor necrosis factor-alpha (TNF-α),interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum at 3, 6 and 14days after combined radiation and burn injury were also observed.RESULTS: All the 160 mice were involved in the analysis of results without deletion. ① Compared with the control group, the mortalities at 5,7, 10, 15, 20 and 30 days in the cervical sympathetic ganglia block group were significantly decreased [control group: 8%, 22%, 32%, 54%, 74%,82%, 90%; cervical sympathetic ganglia block group: 8%, 14%, 16%, 22%,28%, 34%, 56%]. ② Compared with the control group, the numbers of red blood cells, white blood cells and blood platelets in peripheral blood at 7,14 and 21 days after injury in the cervical sympathetic ganglia block group were significantly increased [at 21 days: red blood cells: 23.21×1012 L-1, 14.58×1012 L-1; blood platelet: 16.87×1011 L-1, 12.57×1011 L-1; white blood cells: 20.65×109 L-1, 14.58×109 L-1]. ③ The levels of TNF-α, IL-1β andIL-6 in serum at 3, 6 and 14 days after injury in the cervical sympathetic ganglia block group were significantly decreased as compared with those in the control group [at 14 days: TNF-α: 189, 365 ng/L; IL-1β: 14, 23 ng/L;IL-6: 70, 132 ng/L].CONCLUSION: Cervical sympathetic ganglia block can significantly decrease the mortality of animals with combined radiation and burn injury,and it is an easy and effective method to treat serious trauma, and the mechanism may be realized through accelerating the recovery of hematopoietic function and suppressing the excessive inflammatory reaction.
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<p><b>AIM</b>To investigate the antioxidant mechanisms of propylene glycol mannate sulfate (PGMS) in hyperlipidemic rats.</p><p><b>METHODS</b>Male Wistar rats were given high lipid emulsion diet to establish hyperlipidemic model. PGMS was given every day at different doses (37.8 and 75.6 mg.kg-1, ig) to hyperlipidemic rats for three weeks. In addition, diethyldithiocarbamate (DDC) was given 200 mg.kg-1.3 d-1 (i.p.) to inhibit SOD activity. Then, the MDA content was examined using TBA method to show the oxidation level, and the activities of SOD, GSH-Px and CAT were examined following the kit protocols to indicate the capability of eliminating OFR. RT-PCR was applied to study the expression of Cu, Zn-SOD mRNA in rat liver.</p><p><b>RESULTS</b>The MDA content of PGMS treatment groups decreased markedly compared with hyperlipidemic group, and the activities of SOD, GSH-Px and CAT increased distinctly. Cu, Zn-SOD mRNA expression was significantly increased by PGMS treatment. Furthermore, the application of DDC(the SOD inhibitor) reduced total SOD activity and Cu, Zn-SOD mRNA expression induced by PGMS, and the content of MDA increased correspondingly.</p><p><b>CONCLUSION</b>PGMS can induce the activities of antioxidant enzymes and the mRNA expression of Cu, Zn-SOD, which contribute to the elimination of oxygen free radical. This may explain the molecular mechanism of antioxidant effects of PGMS.</p>