Objective To evaluate the effect of dexmedetomidine and small dose of ketamine on the expression of P2X4 receptor (P2X4 R) mRNA and P2X7 receptor (P2X7R) mRNA in the dorsal root ganglion of rats with neuropathic pain.Methods Ninety male Sprague-Dawley rats,aged 6-9 weeks,weighing 180-220 g,were randomly divided into 5 groups (n =18 each):sham group (group S),chronic constrictive injury group (group CCI),dexmedetomidine group (group D),ketamine group (group K) and dexmedetomidine + ketamine group (group DK).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 400 mg/kg.Neuropathic pain was induced by CCI in CCI,D,K and DK groups.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1mmintervals with 4-0 silk thread.In group S,the sciatic nerves were only exposed but not ligated.In D,K and DK groups,dexmedetomidine 50μg/kg,ketamine 10 mg/kg and dexmedetomidine 25μg/kg + ketamine 5 mg/kg were injected intraperitoneally,respectively,while the equal volume of normal saline was injected in S and CCI groups,once a day for 14 consecutive days after CCI.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI,and 3,7 and 14 days after CCI.Six animals were sacrificed after measurement of pain threshold at 3,7 and 14 days after CCI and the lumbar segments (L4-6) of the dorsal root ganglion were removed for determination of P2X4 R mRNA and P2X7 R mRNA expression by RT-PCR.Results Compared with group S,MWT and TWL were significantly decreased at 3,7 and 14 days after CCI in groups CCI,D,K and DK,the expression of P2X4R mRNA and P2X7R mRNA was up-regulated at 3,7 and 14 days after CCI in groups CCI,D and K,and the expression of P2X4 R mRNA and P2X7 R mRNA was up-regulated at 3 and 7 days after CCI in group DK (P ＜ 0.05).Compared with group CCI,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and P2X7 R mRNA was down-regulated at 3,7 and 14 days after CCI in groups D,K and DK (P ＜ 0.05).Compared with D and K groups,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and P2X7 R mRNA was down-regulated at 3,7 and 14 days after CCI in group DK (P ＜ 0.05).Conclusion The mechanism by which the combination of dexmedetomidine and small dose of ketamine produces a synergistic antinociception in rats with neuropathic pain may be related to down-regulation of the expression of P2X4 R mRNA and P2X7 R mRNA.

Objective To evaluate the effects of dexmedetomidine on the activity of cAMP response element binding protein (CREB) and c-fos in the spinal dorsal horn in a rat model of neuropathic pain.Methods Fifty-four adult male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =18 each):sham operation group (group S),chronic neuropathic pain group (group C) and dexmedetomidine group (group D).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The sciatic nerve was exposed and 4 ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread in C and D groups.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until 1 day before the animals were sacrificed,while the equal volme of normal saline was injected instead of dexmedetomidine in S and C groups.Paw withdrawal threshold to mechanical stimulation with yon Frey filament (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured on 1 day before operation and 3,7 and 14 days after operation.The animals were sacrificed after measurement of MWT and TWL.Their lumbar segments (L4-6) of the spinal cord were removed for measurement of the expression of phosphorylated CREB (pCREB) and c-fos by immunohistochemistry.Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the expression of pCREB and c-fos was up-regulated on 3,7 and 14 days after operation in C and D groups (P ＜ 0.05).Compared with group C,MWT was significantly increased,TWL was prolonged,and the expression of pCREB and c-fos was down-regulated on 3,7 and 14 days after operation in group D (P ＜ 0.05).MWT was significantly lower,and TWL was shorter on 3,7 and 14 days after operation than on 1 day before operation in C and D groups (P ＜ 0.05).MWT was significantly lower,TWL was shorter,and the expression of pCREB and c-fos was higher on 7 and 14 days after operation than on 3 days after operation in C and D groups (P ＜ 0.05).MWT was significantly higher,TWL was longer,and the expression of pCREB and c-fos was lower on 14 days after operation than on 7 days after operation in C and D groups (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine reduces neuropathic pain is related to inhibition of the activity of CREB and c-fos in the spinal dorsal horn of rats.

Objective To investigate the effects of Sulfotanshinone Sodium Injection (SSI) on neuropathic pain in rats.Methods One hundred and eight adult male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =36 each):sham operation group (group S) ; chronic constrictive injury (CCI)group; group SSI.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.In groups CCI and SSI,4 ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread according to the method described by Bennett et al.In group S,the right sciatic nerves were exposed,but not ligated.In group SSI,SSI 25 mg/kg was injected intraperitoneally once a day starting from the end of operation until one day before the animals were sacrificed,while the rats received the equal volume of normal saline (5 ml/kg) instead of SSI in groups S and CCI.Twelve animals in each group were chosen at 1 day before operation and 3,7 and 14 days after CCI (T1-4) to measure mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL).Six rats in each group were sacrificed at T2-4 after measurement of pain threshold,and their lumbar segnents (L4-6) of the spinal cord were immediately removed for determination of Bcl2 and caspase-3 expression in spinal dorsal horn (by immune-histochemistry),and MDA content and SOD activity (by spectrophotometry) in spinal cord.Results Compared with group S,PWT was significantly decreased,PWL was shortened,the expression of Bcl-2 and caspase-3 was up-regulated,MDA content was increased and SOD activity was decreased at T2-4 in groups CCI and SSI (P ＜ 0.05).Compared with group CNP,PWT was significantly increased,PWL was prolonged,the expression of Bcl-2 was up-regulated,the expression of caspase-3 was downregulated,MDA content was decreased and SOD activity was increased at T2-4 in group SSI (P ＜ 0.05).Conclusion SSI can mitigate neuropathic pain in rats and inhibition of oxidative stress in spinal cord tissues and reduction of apoptosis in spinal dorsal horn neurons are involved in the mechanism.

Objective To evaluate the effect of dexmedetornidine on the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) in the spinal cord in rats with neuropathic pain (NP).Methods One hundred and eight male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly assigned into 3 groups (n =36 each):sham operation group (group S),NP group and dexmedetomidine group (group D).NP was induced by chronic constrictive injury in anesthetized rats.Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.In group S,the right sciatic nerves were exposed,but not ligated.Dexmedetomidine 50 μg/kg was injected intraperitoneally once a day from the onset of operation to one day before the rats were sacrificed in group D,while the equal volume of normal saline was injected in groups S and NP.Mechanical withdrawal threshold (MWT) and thermal pain threshold (TPT) were measured on the day before operation (T0) and 3,7,and 14 days after operation (T1-3).After measurement of pain threshold at T1,T2 and T3 after operation,the L4-6 segments of the spinal cord were removed for determination of the expres-sion of TLR4 and NF-κB mRNA (by RT-PCR) and the expression of TLR4 and NF-κB in spinal dorsal horn (by immuno-histochemistry).Results Compared with group S,MWT and TPT were significantly decreased and the expression of TLR4,NF-κB and TLR4 and NF-κB mRNA was up-regulated after operation in groups NP and D (P ＜ 0.05).Compared with group NP,TPT and MWT were significantly increased and the expression of TLR4,NF-κB,TLR4 mRNA and NF-κB mRNA was significantly down-regulated after operation in group D (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine attenuates NP in rats is related to inhibition of the expression of TLR4 and NF-κB in rat spinal cord.

OBJECTIVETo investigate whether aristolochic acid can be transported into human kidney proximal tubular cell (HKC) and its potential mechanism.

METHODSIntracellular aristolochic acid was measured by liquid chromatography-tandem mass spectrometry. The release of lactate dehydrogenase (LDH) induced by aristolochic acid in the presence of organic anion transporter inhibitor (probenecid) or organic cation transporter inhibitor (tetraethylammonium) was evaluated. The effects of probenecid on aristolochic acid induced connective tissue growth factor (CTGF) mRNA and protein expression were also examined by real time polymerase chain reaction and Western blot, respectively.

RESULTSAristolochic acid was detected in the suspension of the denatured HKC after incubation with aristolochic acid sodium salt. The release of LDH from HKC, which was induced by 60 mg/L aristolochic acid sodium salt, was significantly inhibited by 1 mmol/L probenecid (P < 0.01), but not by 1 mmol/L tetraethylammonium. The increased CTGF mRNA and protein expression in HKC stimulated by 40 mg/L aristolochic acid sodium salt was significantly down-regulated by 1 mmol/L probenecid (P < 0.05), with an inhibition rate of 16% and 21%, respectively.

CONCLUSIONAristolochic acid can be transported into HKC by organic anion transport system, and then exerts its biological effects.

Aristolochic Acids ; metabolism ; Connective Tissue Growth Factor ; metabolism ; Epithelial Cells ; metabolism ; Humans ; Kidney ; physiology ; Organic Anion Transporters ; metabolism

Objective To investigate the changes of lead,zinc,copper,iron and calcium in blood of chronic poisoned infantal mice.(Methods) Forty-eight 21 day-old kunzea mice were randomly divided into 4 groups,each having 12 mice.Distilled water group was as control group and other three lead acetate poisoning groups had a dose of 10,20,40 mg/kg,respectively.The poisoning was carried out by lavage once a day,and consecutively for 46 days.Eyeballs of mice were picked then for blood sampling,and BS trace element analysis grapher was used to determine level of lead,zinc,copper and iron.Level of calcium was measured by Dimentional-RXL auto-biochemistry analysis meter.Results The lead and zinc levels in poisoned mice blood were increased with increasing lead acetate level administration,while zinc level changed inversely with lead acetate level.Significant differences were shown among control group and poisoning groups in terms of lead(P0.05).Conclusion Lead posioning can lead to zinc decreasing and copper(increa)-sing,which suggests that zinc works as a poential antidote of lead poisoning.

Both sides of the picornavirus genome have 5'-untranslated region (5'UTR) and 3'- untranslated region (3'UTR). This study demontrated that both the 5'-and 3'-UTR can form complex structures, such as stem-loop, clover and pseudoknot structure, These structures play an important role in the regulaton of the replication and translation of the viruses. This article reviewed the progress of research on the structure and function of picornavirus' 3'-UTR over recent years.
3' Untranslated Regions ; Animals ; Humans ; Nucleic Acid Conformation ; Picornaviridae ; chemistry ; genetics ; metabolism ; Picornaviridae Infections ; virology ; RNA, Viral ; chemistry ; genetics ; metabolism

Partial nature of "promoting blood circulation and dieresis" of Salvia Miltiorrhizain was initially demonstrated by investigating the regulation effect of AQP2 expression in kidney of trauma blood stasis model rats with the Salvia Miltiorrhizain so as to provide guidance for its clinical deployment of administration. Random allocation was taken to averagely divide 30 SD rats into two groups: 10 rats in normal group and 20 rats in blood stasis syndrome group. Trauma blood stasis rat model was established by quantitatively beating. Then the rat model group was divided into model group and salvia group. After 7 days of treatment, the rat kidney AQP2 expression was detected, the content of urine AQP2 was compared and the damaged local muscle and kidney pathological changes were observed by immunohistochemical method and western blot method. Compared with that of the normal group, rats in model group had inflammatory cells infiltration, blood stasis and edema of the injured local muscles and up-regulated AQP2 expression, decreasing urinary output, and kidney tissues blood stasis and edema (P < 0.05). On the other hand, compared with that of the model group, those parameters of rats in salvia group were all decreasing except urine output (P < 0.05). Such result indicated that Salvia Miltiorrhiza can reduce trauma blood stasis rat content of urine AQP2 and down-regulated AQP2 expression in kidney tissue, so as to reduce the reabsorption of water by renal tubular and increase urine output. The promoting blood circulation effect of Salvia Miltiorrhizain can alleviate the degree of the damaged tissue edema and encourage urine drainage. This therapy is closely related to the effect of regulating AQP2 in kidney by salvia, so the purpose of this study by verifying "promoting blood circulation and diuresis" as the mechanism for the regulation effect of the salvia on AQP2 expression.
Animals ; Aquaporin 2 ; genetics ; metabolism ; Blood Circulation ; drug effects ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; blood supply ; drug effects ; metabolism ; physiopathology ; Kidney Diseases ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; Rats ; Salvia miltiorrhiza ; chemistry

Objective To explore the clinical signiifcance of combined detection of thyroid stimulating hormone (TSH) and free thyroxin (FT4) in dried blood spots in screening for congenital hypothyroidism (CH) in neonates. Methods The TSH and FT4 levels in dried blood spot were measured by time-resolved lfuorescence immunity in live born neonates from June to December 2013. If the screening was positive, the blood was drawn and the serum TSH and FT4 were measured and compared with the results from dried blood spots. Results In a total of 31 199 neonates screened, 12 cases were diagnosed with CH and the prevalence rate of CH was 1/2 600;4 cases were hyperthyropinemia and no pituitary CH was detected. There was no signiifcant difference between TSH or FT4 levels in dried blood spot and those in serum in neonates diagnosed with CH (P>0.05). Conclusions Combined detection of TSH and FT4 in dried blood spot can be used for neonatal screening of CH. It can be applied for early distinguishing CH from hyperthyropinemia, and also helpful for early diagnosis and treatment of central CH.

Objective To study the feasibility of Video-assisted thoracoscopic thymectomy and the long term result of thoracoscopic thymectomy for myasthenia gravis. Methods 9 cases of thymus related disease were selected to undergo thymectomy though thoracoscopic approach from August 1996 to April 2001.Patients were followed up through outpatient service and telephone consultation. Results Of the 9 cases 2 cases were diagnosed as thymus cysts,1 cases thymoma,1 case malignant thymoma,1cases thymus carcinoma and 4 cases myasthenia gravis.Of the 4 cases of myasthenia gravis,3 cases were typeⅠ and 1 case was typeⅡb according to the modified Osserman classification.After thoracoscopic thymectomy 75% of patients had long-term good responses to surgery.The operation of one case of malignant thymoma was converted to lateral thoracotomy.One case of malignant thymoma with myasthenia gravis relapsed and reoperated through open thoracotomy . Conclusions video-assisted thoracoscopy can be usd to treat seleted thymic diseases .The results of video-assisted thoracoscopic thymectomy for mysthenia gravis is almost comparable with traditional open thoracotomy