Cadmium ; pharmacology ; Cells, Cultured ; Heat-Shock Proteins ; biosynthesis ; Humans ; Metallothionein ; biosynthesis ; Ubiquitin ; biosynthesis

Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.

BACKGROUND: Endothelin and nitrogen monoxide (NO) which are regarded as a pair of factors to maintain equilibrium between vascular stress and hemodynamics have different responses during various diseases. It is the key point for the treatment of atherosclerosis to find out the effect and pathophysiological mechanism of hyperlipemia on endothelial cells, and seek the methods and drugs for protecting vascular endothelin.OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on contents of plasma endothelin and NO and analyze its regulative mechanism.DESIGN: Randomized controlled animal study.SETTING: College of Acupuncture and Moxibustion, Hunan University of Traditional Chinese Medicine.MATERIALS: A total of 60 healthy New Zealand white rabbits weighing 1.5-2.5 kg of both genders were selected in this study. Herbal cake was made of danshen, shanzha, yujin, dahuang and zexie, which were crushed into powder according to a certain ratio. Then, vinegar was added to make paste which was 5-8 mm in diameter and 2-3 mm in depth. Moxa cone:(Shenjiu 300) was provided by Suzhou Dongfang Airong Factory (type:Dongfang I; batch number: 20021212).METHODS: The experiment was carried out in the Experimental Animal Center of Hunan University of Traditional Chinese Medicine between November 2003 and October 2004. All rabbits were randomly divided into 4 groups: blank control group, hyperlipemia model group, direct moxibustion group and herbal cake-separated moxibustion group with 15 in each group. Except blank control group, rabbits in other three groups were fed with high fat forage to establish hyperlipemia models. Two groups of acupoints were acupunctured alternatively: Group Ⅰ: Juque (CV14), Tianshu (ST25) at bilateral sides, and Fenglong (ST 40) at bilateral sides; Group Ⅱ:Xinshu(BL15),Ganshu(BL18) and Pishu(BL20), at bilateral sides respectively.On the first day, moxa cone was directly adherent to acupoints of rabbits in direct moxibustion group and lighten for acupuncture, but in herbal cakeseparated moxibustion group, moxa cone which was gotten rid of the carriage was adherent to herbal cake which was put on acupoints and lighted for acupuncture. Each acupoint was acupunctured for 4 successive dosages for once a day. On the next day, the other group of acupoints was acupunctured.The course was 40 days. Rabbits in other two groups were not treated with any ways. On the 41st day, contents of plasma endothelin and NO were measured in each group with radio-immunity method and nitrate-reductase reduction method, respectively.MAIN OUTCOME MEASURES: Contents of plasma endothelin and NO of rabbits after 40-day treatment.RESULTS: Five rabbits died because of diarrhoea or other reasons, including 2 in blank control group, 1 in model group, 1 in direct moxibustion group and 1 in herbal cake-separated moxibustion group. Therefore, 55 rabbits were involved in the final analysis. ① Content of plasma endothelin was lower in herbal cake-separated moxibustion group than that in model group [(431.57±63.68), (500.14±75.41) ng/L, P ＜ 0.05], but there was no significant difference between herbal cake-separated moxibustion group and direct moxibustion group [(431.57±63.68), (429.08±77.07) ng/L, P ＞ 0.05]. ② On NO content, there was an increasing tendency of model group ＜ blank group ＜ herbal cake-separated moxibustion group ＜ direct moxibustion, but there was no significant difference between any two groups [(27.17±16.55),(29.39±13.24), (30.24±20.25), (30.47±19.62) μmol/L, P ＞ 0.05].CONCLUSION: Effects of both two methods of moxibustion in the rabbits with hyperlipemia on content of endothelin are significant and similar, but there are no significant effects on NO content.

Objective To explore the value of echo-tracking technique in the detecting the ipsilateral external iliac artery elasticity after gunshot wound in pig limbs.Methods Two-dimensional ultrasound imagings and elasticity parameters of external iliac artery of fifteen pig limbs were obtained respectively,and the results were compared with pre-injury groups.The animals were sacrificed after ultrasonography.Pathological examinations of adjacent external iliac artery of injured pig limbs were analyzed.Results Two-dimensional ultrasound imagings of external iliac arteries had no significant changes post-injury.The changes of elasticity parameters were significiant differences in the injured group comparing with the pre-injured group (P ＜0.05),including the increased stiffness parameter(β),pressure-strain elasticity modulus (Ep)and the decreased arterial compliance(AC).Pathological result showed that the internal elastic lamina of artery detected were flat,endothelial cells came off discontinuously and structure of them were undefined.Conclusions Echo-tracking technique can find the elastic changes of adjacent artery indirect injured by gunshot wound sensitively and which can suggest the occurrence of vascular indirect injury.

OBJECTIVE: To study the effects of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expressions of epidermal growth factor receptor (EGFR) signaling substances phospholipase C gamma-1 (PLC gamma-1), protein kinase C (PKC) and c-myc in gastric mucosal cells. METHODS: Sixty rats were randomly divided into normal group, stomach meridian group, gallbladder meridian group, stomach meridian plus PD153035 group and gallbladder meridian plus PD153035 group. Water-immersion and restrained stress methods were adopted for inducing gastric mucosal injury in the rats. Gastric mucosal cells were separated by using pronase digestion method, and incubated by PD153035, a EGFR inhibitor, and 100 ml/L serum. The expression of PLC gamma-1 in the gastric mucosal cells was tested by enzyme linked-immunosorbent assay (ELISA), while the expression of PKC by isotope incorporate assay and the expression of c-myc by reverse transcription polymerase chain reaction assay (RT-PCR). RESULTS: In gastric mucosal cells, weak expressions of PLC gamma-1, PKC and c-myc were seen in the normal group, and relatively strong expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian group and the gallbladder meridian group, among which, the expressions of PLC gamma-1, PKC and c-myc in the stomach meridian group were the strongest, and there was a significant difference between the stomach meridian group and the gallbladder meridian group (P<0.01). Relative weak expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian plus PD153035 group and the gallbladder meridian plus PD153035 group, and there was a significant difference between the stomach meridian group and the stomach meridian plus PD153035 group (P<0.01). CONCLUSIONS: The serum derived from the rats treated with electroacupuncture at stomach meridian acupoints can activate the EGFR singling pathway, and this provides an evidence for the theory of "relative particularity between meridians and viscera" in traditional Chinese medicine.

OBJECTIVETo investigate the effects of Wuhuang Tangkangling on tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) in serum of patients with type 2 diabetes mellitus (T2DM).

METHODOne hundred cases of type 2 diabetes mellitus patients were randomly divided into two groups. The control group was treated with pioglitazone (15 mg x d(-1)) orally once a day in the morning, combined with insulin subcutaneous injection based on blood glucose level. The treatment group was treated with decoction of Wuhuang Tangkang Ling daily, 8 weeks as a course. TNF-alpha, IL-6, hs-CRP, fasting blood glucose (FBG) and postprandial blood glucose (PBG) were tested for two groups of patients before and after the treatment And other 50 healthy cases were tested for comparison.

RESULTBefore treatment, the level of cytokine, FBG and PBG in the serum of patients with T2DM were significantly higher than healthy cases (P < 0.01). In treatment group, difference between before and after the treatment had statistical significance (P < 0.01); after treatment, difference between treatment group and control group had statistical significance (P < 0.01).

CONCLUSIONWuhuang Tangkangling could significantly decrease the level of TNF-alpha, IL-6, hs-CRP, FBG and PBG in patients with T2DM, and could decrease blood glucose, anti inflammatory, and improve insulin resistance. According to testing these cytokines, a new criteria for evaluating the progress of T2DM and the treatment may be approached.

C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the clinical effect of decoction of invigorating Qi and clearing lung combined standardized myrtol on acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

METHODNinety and eight patients with AECOPD patients were randomly divided into the treatment group and the control group, with 50 cases and 48 cases respectively. All the patients were given the conventional treatment. The control group was treated by standardized myrtol with 3 times a day, 300 mg each time taken orally. The treatment group was given decoction of invigorating Qi and clearing lung with 2 times a day, one dose per day taken orally, combined standardized myrtol (usage as above). After Two weeks, the scores of clinical symptom, blood gas analysis and pulmonary function were observed.

RESULTBoth FEV1 and FEV1% were raised in the two groups after treating. And the treatment group was significantly higher than control group (P < 0.01). PaO2 and PaO2/FiO2 rose, with PaCO2 decreased in the two groups (P < 0.01). PaO2 and PaO2/FiO2 were significantly improved, and PaCO2 was significantly decreased in the treatment group compared to the control group (P < 0.01). In the clinical curative effect comparison aspects, clinical control rates were 42.0% in treatment group and 20.83% in control group respectively, with significant difference between the two groups (P < 0.05). Significant efficiency is 86.0% in treatment group and 52.08% in control group respectively, with significant difference between the two groups (P < 0.01).

CONCLUSIONDecoction of invigorating Qi and clearing lung combined with standardized myrtol can obviously improve clinical symptom, blood gas an analysis and pulmonary function in patients with AECOPD.

Aged ; Blood Gas Analysis ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Lung ; physiopathology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Monoterpenes ; standards ; therapeutic use ; Pulmonary Disease, Chronic Obstructive ; blood ; physiopathology ; therapy ; Reference Standards ; Respiratory Function Tests ; Treatment Outcome

Objective To analyze the prognostic factors associated with three-year survival outcome in patients with serous ovarian adenocarcinoma by classification tree.Methods Retrospectively we analyzed 81 cases with serous ovarian adenocarcinoma who had 3-year clinical outcomes and were hospitalized in People's Hospital from Jan 1991 to Dec 2003 by classification and regression trees(CART)software.Establish the classification tree.Results Among the factors that were associated with the 3-year survival rate,age was the most important factor,other factors in turn were International Federation of Gynecology and Obstetrics(FIGO)stage,lymphoid metastasis,residual size after operation,chemotherapy and pathologic grade.By substitution variable analysis,it was demonstrated that there was cross interaction between age and residual size as well as age and chemotherapy.Conclusion Age,FIGO stage,lymphoid metastasis,residual size after operation,chemotherapy and pathologic grade are important prognostic factors related with three-year survival probability of serous ovarian adenocarcinoma patients.

Objective To explore the clinical effect of traditional Chinese medicine (TCM) dialectical therapy for treatment of gastrointestinal dysfunction in patients with acute lung injury / acute respiratory distress syndrome(ALI/ARDS)undergoing mechanical ventilation. Methods A prospective,randomized controlled trial was conducted. Ninety-six ALI/ARDS patients admitted in intensive care unit(ICU)and treated with mechanical ventilation in Tianjin First Central Hospital were chosen and randomly divided into traditional Chinese medicine(TCM) group and conventional therapy group using a random number table,48 patients in each group. Conventional therapy alone was used in conventional therapy group,and TCM therapy of primarily using Dachengqi decoction combined with conventional therapy was applied in TCM group〔Dachengqi decoction was composed of mongolian milkvetch root 15 g, pilose asiabell toot 15 g,Chinese angelica 10 g,officinal magnolia bark 10 g,tangerine peel 10 g,immature tangerine fruit 10 g,peach seed 10 g,white peony root 12 g,red peony root 12 g,immature bitter orange 6 g,mongolian dandelion herb 30 g,radish seed(stir-fried)30 g,foxtail millet sprout 20 g,barley sprout 20 g,glauber salt 9 g (with water),rhubarb 10 g(added in water at last)〕,one dose orally taken daily for 28 days. The intra-abdominal pressure(IAP),gastrointestinal diseases in TCM symptom score and the incidence of gastrointestinal dysfunction were compared between the two groups before treatment and on the 3rd,6th and 8th day after treatment. Results There were no statistical significant differences in IAP and TCM symptom scores between the two groups before treatment (both P>0.05),but after treatment with the prolongation of therapeutic time the IAP and TCM symptom scores were decreased gradually compared with those before treatment,having reached the valley value on the 18th day and the changes in TCM group were more remarkable〔IAP(mmHg,1 mmHg=0.133 kPa):0.91±0.69 vs. 2.08±0.92, TCM symptom score:48.33±10.41 vs. 88.33±20.21,both P<0.05〕. In the TCM group,the incidences of the untoward symptoms and signs of gastrointestinal dysfunction such as bleeding of stress ulcer,toxic intestinal paralysis, abdominal distension,diarrhea and so on were lower than those in conventional therapy group〔stress ulcer bleeding:16.7%(8/48)vs. 39.6%(19/48),toxic intestinal paralysis:16.7%(8/48)vs. 43.8%(21/48),abdominal distension:10.4%(5/48)vs. 37.5%(18/48),diarrhea:6.3%(3/48)vs. 33.3%(16/48),all P<0.05〕. Conclusion Addition of TCM Dachengqi decoction on conventional treatment can effectively lower the incidence of gastrointestinal dysfunction in treatment of patients with ALI/ARDS undergoing mechanical ventilation.

Objective To investigate the expression of extraeellular signal-regulated protein kinase (ERK1/2)pathway in rat brains with fluorosis and the effects of fluoride on learning and memory of the rats,and to reveal the mechanisms of damaged nervous system resulted from the toxicity of the ion.Methods Seventy-two SD rats were divided into 3 groups and 24 rats were in each group.Three groups were fed respectively with different concentrations of fluoride(NaF)for 6 months to establish rat models with fluorosis.Controls were fed with tap water (NaF＜0.5 mg/L):lower and higher concentration group were fed with water containing NaF(5,50 ms/L).Animals are sacrificed after 6 months of treatment with fluoride and the dissected brains were kept for analysis.The protein levels of ERK1/2 in rat brains were detected by Western-blotting and the mRNA level by RT-PCR. The spatial learning and memorizing ability was measured by Morris water maze test. Results The ERK1/2 protein in control group,lower and higher concentration group was 0.944±0.10,1.253±0.02,1.953±0.07,the differece being statistieally sighificant between any two groups (P ＜ 0.05). The phospho-ERKl/2 protein in control group,lower and higher concentration group was 0.73±0.08,0.77±0.07,1.28±0.11,the differece being statistieally sighificant between any two groups(P ＜ 0.05);the activation rate of phospho-ERK1/2 in lower and higher concentration group [(68.4± 3.8)%,(64.1±3.2)%] was decreased compared to control group[ (82.3±10.7)%],the differece being significant(P ＜ 0.05). In the navigation trial,longer escape latencies of lower concentration group on the second, the third,the fifth and the sixth day were observed[ (46.0±8.0),(24.0±2.7),(8.9±5.3),(7.4±4.1 )s] compared to the control[ (39.3±6.9),(19.1±9.1 ),(8.3±3.4),(4.8±2.7)s],the differece being significant (P ＜ 0.05 or ＜ 0.01 );the similar results were also observed in the higher concentration group[ (36.9±16.8),(37.7±12.9), (19.7±7.6),(12.2±5.7 )s],and the escape latencies of the higher concentration group on the third,the fifth and the sixth day were longer than that in lower concentration group. In the probe test,the rats took more time to reach the first cross in lower and higher concentration group[(1.17±0.75),(4.18±1.10)s] than control group[ (5.89± 0.56 ) s ],the differece being significant (P ＜ 0.05 or ＜ 0.01 ) ;stayed shorter [ ( 17.05±4.25 ),(18.20±4.57 ) s ] than control [(25.37±5.65 )s ] in platform area (P ＜ 0.01 );the activation rates of ERK1/2 were directly correlated with the time taken to reach the first cross platform located in the probe test(r = 0.364,P ＜ 0.05) and the activation rates were also directly correlated with the escape latencies on the sixth day(r = 0.497,P ＜ 0.05). Conclusion Long-term exposure of excessive fluoride induces the change of expression and activating rate of the ERK1/2 in rat brains,leading to the decreased capacity of learning and memory.