Objective To investigate the effect of ketamine, the NMDA receptor antagonist, on inducible nitric oxide gynthase (iNOS) mRNA expression in the spinal cord during the development of morphine tolerance. Methods Thirty Kunming mice weighing 18-22 g were randomly divided into 5 groups ( n = 6 each): A control group received normal saline (NS) only; B chronic morphine tolerance group received subcutaneous morphine 10 mg?kg-1 followed by IP NS after an interval of 30 min, twice a day for 9 days and C, D, E ketamine groups received subcutaneous morphine 10 mg?kg-1 followed by IP ketamine 5 (group C) or 10 (group D) or 20 (group E) mg?kg-1 after an interval of 30 min, twice a day for 9 days. One hour after the last drug administration the animals were decapitated and the lumbar enlargement of the spinal cord was isolated and the iNOS mRNA expression in the spinal cord was detected by RT-PCR. Results Expression of iNOS mRNA was not detectable in group A but increased dramatically in group B. The iNOS mRNA expression was significantly lower in group D and E (ketamine 10 and 20 mg?kg-1 IP) than in group B and C (ketamine 5 mg?kg-1) . Conclusion Ketamine antagonizes the development of chronic morphine tolerance in mice through down-regulation of iNOS mRNA expression in the spinal cord.

Objective Glutarnic acid, an important excitatory neurotransmitter, plays an important role in morphine dependence and tolerance. Astrocyte (AST) takes up giutamic acid which is transformed into glutamine, the precursor of GABA, by means of intracellular glutaminase. The aim of thin study was to investigate the effect of ketamine on glutamate release in cultured spinal ASTs chronically treated with morphine. Methods ASTs were isolated from 1-3 day old SD rats and divided into 8 groups : control group and group A, B1, B2, B3 , C1, C2, C3. The isolated ASTs were cultured and incubated for 48h in the presence (group A, B1-3, C1-3) and absence (control group) of 10?mol?L-1 morphine.Then the ASTs were transferred to liquid culture medium Neurobasal / B27 containing no serum. No drug was added in group A. Morphine 0.1 ,1 or 10?mol?L-1 was added in group B1-3 and ketamine 0.4, 4 or 40?mol?L-1 in group C1-3. After being incubated for 15 min, naloxone 10?mol?L-1 was added in group B1-3 and C1-3. After another 30 min incubation the gluamate concentration in supernatant was measured using HPLC. Results There was no significant difference in glutamate concentration between control group and group A ( P

Objective Recent studies have shown that activation of spinal astrocytes (ASTs) may be involved in the development of morphine tolerance. The purpose of this study was to investigate the effect of ketamine (K) on spinal ASTs in mice tolerant to morphine (M) .Methods Thirty Kun-Ming mice of both sexes weighing 18-22 g were randomly divided into 5 groups of six animals each : (A) control group received only subcutaneous (s.c.) and intraperitoneal (i.p.) normal saline (NS); (B) chronic M-tolerance group received M 10 mg?kg-1 s.c. followed after 30 min by NS 10 ml?kg-1 i.p. twice a day (at 8:00 and 17:00) for 9 days;(C), (D), (E) K group received M 10 mg?kg-1 s.c. followed after 30 min by K 5 mg? kg-1(C), 10 mg?kg-1 (D) or 20 mg?kg-1 (E) i.p. twice a day for 9 days. Pain threshold was estimated by measuring paw withdrawal response to Von Frey filament stimulation every other day (1st, 3rd, 5th, 7th, 9th) In after second administration of drugs. The percentage of maximal possible effect (MPE% ) was calculated : MPE% = [ (test group PWTV - control group PWTV) / (15 - control group PWTV)] ? 100% (PWTV = paw withdrawal threshold value). On the 9th day after pain threshold was measured the animals were sacrificed and lumbosacral segment of spinal cord was removed. The changes in spinal ASTs were detected by immunohistochemistry. The average areas of GFAP immuno-reactive cells in the dorsal horn were measured to show the degree of spinal AST activation. Results 1. MPE% was 0 at all time points in group A. In group B MPE% was 42.8% on the 1st and 3rd day and gradually decreasing on the 5th and 7th day and became 0 on the 9th day signifying full development of morphine tolerance. In group C the change in MPE% was almost the same as in group B. In group D and E MPE % tended to decrease but was still above 30% at all time points signifying that ketamine 10 and 20 mg?kg-1 could partly antagonize the development of morphine tolerance. 2. In group B the staining of GFAP immuno-reactive cells was heavier and the average areas were significantly larger than in group A (P

0.05) and group TP2 ( P

Objective To investigate the effects of propofol the expression of inducible nitric oxide synthase (iNOS) in the spinal cord in rats with chronic neuropathic pain. Methods Forty adult Wistar rats of both sexes weighing 200-220 g were used in this study. Chronic neuropathic pain was produced by loose ligatures placed on the left sciatic nerve. Propofol or normal saline (NS) was given intraperitoneally (i.p. ) once a day for 6 days, seven days after sciatic nerve ligation. The animals were randomly divided into 4 groups (n = 10) : group Ⅰreceived NS 50 ml?kg-1 i.p. but no sciatic nerve ligation; group Ⅱ received sciatic nerve ligation and NS 50 ml?kg-1 i.p. ; group Ⅲ and Ⅳ received sciatic nerve ligation and propofol 50ml?kg-1 (Ⅲ) or75ml?kg-1 (Ⅳ) i.p. . Withdrawal threshold of both hind paws to Von Frey filaments was measured on the 6th , 10th and 12th days after sciatic nerve ligation. The animals were then sacrificed and the lumbar segment (L4-5) of the spinal cord was removed for the detection of iNOS mRNA expression by RT-PCR technique on the 12th day. Results The withdrawal threshold to Von Frey filament of both hind paws was significantly higher on the 10th and 12th days in the two propofol groups (group Ⅲ and Ⅳ) than in group Ⅱ(P

This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Allopurinol ; therapeutic use ; Febuxostat ; Gout ; blood ; drug therapy ; Gout Suppressants ; therapeutic use ; Humans ; Thiazoles ; therapeutic use ; Uric Acid ; blood

OBJECTIVETo investigate the role of autophagy in acute lung injury (ALI) caused by multiple trauma in rats via pretreat with 3-methyladenine (3-MA).

METHODSForty-five Sprague-Dawley male rats, with age of 4 months and body weight of 250-300 g,were randomly divided into three groups. In the sham group, the rats received sphenotresia only;in the control group, the rats were made model of femur shaft fracture combined with brain injury, and treated with physiological saline by abdominal cavity at 1 hour before making model; in the 3-MA group, the rats were made model of femur shaft fracture combined with brain injury,and treated with 3-MA of 10 mg/kg by abdominal cavity at 1 hour before making model. Histologic changes and the concentration of related inflammatory factors in the damaged lung tissue were examined at 48 h after opteration, at the same time, the effect of 3-MA on the expression of LC-3 II and Beclin-1 was examined through reverse transcriptase polymerase chain reaction technique (RT-PCR).

RESULTSCompared with sham group, LC-3 II and Beclin-1 level in control group at 48 h after operation were obviously increased (P < 0.01). Compared with control group, LC-3 II and Beclin-1 level in 3-MA group at 48 h after operation were obviously decreased (P < 0.01). Compared with sham group, the level of proinflammatory cytokines (TNF-α and IL-6) in control group obviously enhanced (P < 0.01). Compared with control group, above items in 3-MA group was obviously lower (P < 0.01). Compared with control group,the histopathological damage of lung in 3-MA group obviously reduced (P < 0.01).

CONCLUSIONAutophagy can aggravate the acute lung injury caused by fracture of shaft of femur combined with brain injuries,but 3-MA can reduce tissue damage by inhibiting the autophagy and inflammatory response.

Acute Lung Injury ; prevention & control ; Adenine ; analogs & derivatives ; therapeutic use ; Animals ; Apoptosis Regulatory Proteins ; analysis ; Beclin-1 ; Interleukin-6 ; analysis ; Lung ; chemistry ; immunology ; pathology ; Male ; Multiple Trauma ; complications ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis

Objective To observe reverse effect of anisodamine to the adverse effect of remifentanil during enteroscopy without pain for patients with bradycardia .Methods Sixty‐five patients with bradycardia were selected and divided randomly into group C (n=21 ,control group)、group A1 (n=22 ,anisodamine by instillation) and group A2 (n=22 ,anisodamine by continous infusion) .In‐duction :Intravenous etomidate 0 .08 mg/kg ,propofol 1 .00 mg/kg and remifentanil 0 .10μg/kg in 3 groups .Ten mg anisodamine in‐fused by instillation before induction in group A1 ,5 mg anisodamine infused by instillation before induction and continous infused by 0 .25 mg/min in group A2 .Maintenance:All group received propofol 4 mg · kg‐1 · h‐1 ,remifentanil 0 .05 μg · kg‐1 · min‐1 after un‐dergoing enteroscopy .stopping pumping propofol when colonoscopy reached ileocecal junction ,and we took off remifentanil when colonoscopy withdraw to decending colon .Then we observed and recorded HR ,SpO2 ,MAP ,dosage ,fluid infusion ,induction time , check time ,analepsia time ,degree and of enterospasm and numbers of cases and side effect at T0 (before induction) ,T1 (beginning of operation) ,T2 (into the transverse colon) ,T3 (to the ileocecal junction) ,T4 (exit) .Results There were no significant difference a‐mong 3 groups of induction time .Compared with group A1 and group A2 about check time and analepsia time ,group C was much shorter .The HR of group A1 and A2 were more stable than group C at T2 、T3 .At T1 、T2 ,the fluctuation of HR of group A2 was less than that of group A1 .There was obviously different among 3 groups of propofol′s dosage ,operation time and enterospasm ,the effect of group A1 and group A2 were better .There was statistically significant in number of cases of body movement between group A1 (1/22)and group C(4/21) ,there was also statistical significance between group A1 ,group A2 and group C(P<0 .05) .Conclusion There are no difference between 2 methods about relieving enterospasm ,refraining intestinal angina ,shortening operation time , saving anesthetic dosage .Effect of continous pumping to undulation of HR may be more stable .

A 28-year-old male patient presented with a 4-year history of a solitary brown mass, and a 1-year history of multiple small papules on the left chest. Skin examination showed a quasi-round brown firm mass measuring about 1.2 cm × 1.1 cm × 1.0 cm in size on the left chest, and several brown papules with diameters ranging from 3 to 5 mm on the right side of the mass; no enlarged lymph nodes were detected in the left axilla on palpation. The mass and papules were completely resected, and histopathological examination showed clustered nevus cells in the superficial dermis of the mass and small papules, and the diagnosis of intradermal nevus was considered. There was a desmoplastic nodule in the mass, nevus cells were scattered among the fibers in the nodule, and giant nevus cells were also observed; the nevus cells in the nodule were relatively larger, epithelioid or spindle-shaped with round or spindle-shaped nuclei, obvious nucleoli, and rare mitotic figures. Immunohistochemical study showed that the nevus cells in both the intradermal nevus and proliferative nodule were positive for S100; the nevus cells in the superficial dermis of the intradermal nevus were positive for Melan-A and HMB45, while the nevus cells in the proliferative nodule were negative for Melan-A and HMB45; both the intradermal nevus and proliferative nodule tissues showed a Ki-67 index of 1%, positive staining for CD34, but negative staining for P16 and P63. Finally, the patient was diagnosed with intradermal nevus associated with desmoplastic nodule.

Objective To research and construct dynamic electrocardiograph (ECG) simulation model/algorithm to simulate different kinds of clinical ECG,where the heart rate can be infinitely variable,and to develop one platform for fast-demo and analysis of theoretical wave based on this algorithm which can be implemented in ECG training and teaching. Methods According to different characteristics decoupled one complete ECG wave to 4 parts,including P-wave,PR-section,QT -wave and TP -section. P -wave and QT -wave database were set up accordingly to find the relationship algorithm between PR-section and heart rate,TP-section and heart rate. With the synthesis work of the algorithm and clinical diagnosis theory,ECG simulation mathematical model /algorithm,dynamic link library.(dll) and software interface were developed by C++. Results Through comparing the ECG simulation results with clinical samples,the veracity and validity of the mathematical model/algorithm was verified. Conclusion The software module based on this model/algorithm is very valuable for ECG training and teaching in clinic,and can be implemented in the development of more advanced ECG relative software and devices.