Objective To investigate the different changes in the regulation and gene expression of mu opioid receptor (MOR) in rat brain after acute and chronic morphine dependence.Methods Forty male SD rats weighing (210?35)g were randomly divided into five equal groups of eight animals each: (1) control; (2) acute dependence: (3) chronic dependence;(4) acute abstinence; (5) chronic abstinence. In acute dependence group rats received eight consecutive subcutaneous injection of morphine 5mg?kg-1 at 2h interval. In chronic dependence group morphine was injected subcutaneously three times a day(8:00, 15: 00, 22:00) for six days. The doses of morphine were 5, 10, 20, 40, 50, 60 mg? kg-1?day-1 from the 1st day to the 6th day respectively. In the two abstinence groups, the withdrawal syndromes were induced by intraperitoneal naloxone 5 mg ? kg-1. The rats in control group received saline. 30 min after the end of all procedures the animals were decapitated on ice. Brain was removed immediately and kept in liquid nitrogen. The Bmax and Kd values of 3H-DAMGO saturation binding to MOR were measured by Scatchard analysis. The gene expression of MOR was appraised by RT-PCR. Results (1) In the acute dependence group the Bmax value(the specific binding capacity of MOR) significantly increased and the affinity decreased. After abstinence the Bmax value returned to normal, but the affinity was still low. In chronic dependence and abstinence groups Bmax value decreased significantly and there was no change in Kd value. (2) The level of MOR mRNA increased significantly in acute dependence group and returned rapidly to normal after abstinence . In chronic dependence and abstinence groups the transcription of MOR was significantly lower than in control group. Conclusions The modulation of MOR in rat brain is different between acute and chronic dependence and there must be similar post-receptor mechnism involved.

Objective:To assess whether intrathecal orphanin FQ can develop the antinociceptive effect tolerance,and whether there is a cross tolerance between the antinociceptive effect of intrathecal orphanin FQ and the ? opioid receptor agonist morphine.Methods: Tail flick test was used to observe the change of antinociceptive effect after orphanin FQ/morphine intrathecal microinjection into the rats tolerant to acute or chronic morphine/orphanin FQ.Results:Like morphine,large dosage of continuous intrathecal orphanin FQ microinjection produced tolerance to the antinociceptive effect,but there was no apparent cross tolerance between the orphanin FQ and morphine; Hyperalgesic response was found in morphine tolerant rats,but not in orphanin FQ tolerant rats.Conclusion:Lack of cross tolerance between the antinociceptive effect of intrathecal orphanin FQ and morphine indicates that the mechanism of tolerance to orphanin FQ may differ from that to morphine; The antinociceptive effect of intrathecal orphanin FQ may be largely related with its specific receptor in the spinal cord.

Objective: To observe the effects of OFQ on endomorphin-1 in pain modulation. Methods: OFQ and endomorphin-1 were microinjected intracerebroventricularly or intrathecally in rats. The pain thresholds were measured by tail-flick test and acetic-acid induced twitching test, and the changes of antinociceptive effects induced by endomorphin-1 were observed. Results: OFQ antagonizing endomorphin-1 antinociception at the supraspinal level, while enhancing at the spinal level were observed. Conclusion: OFQ has functional effects on endomorphin-1 in pain modulation,both in the brain and the spinal cord. The mechanisms of its effect may be different.

Objective:To observe the development of tolerance and dependence to endomorphin 1(EM 1) and its regulation on ? opioid receptor(MOR) in rat brain,providing references for the mechanism of the EM 1 dependence. Methods: Totally 60 SD rats were randomly divided into saline, acute EM 1 treatment and chronic EM 1 treatment groups. For acute EM 1 treatment, rats were injected intracerebroventricularly with 10 ?g/kg EM 1 30 min prior to sacrifice. The chronic group were treated with EM 1 daily administration at 8:00 and 15:00 starting with 10 ?g/kg on day 1 to 50 ?g/kg on day 9. After chronic EM 1 treatment on day 1, 3, 6 and 9, the antinociceptive AD 50 or catatonic ED 50 values were determined by modified Dixon's method. The B max and K d values of 3H DAMGO saturation binding to MOR were measured by Scatchard analysis. The gene expression of MOR was appraised by RT PCR. Results:(1) EM 1 chronic treatment produced a high degree of tolerance to the antinociceptic and catatonic effects on the 3rd day (3.1 fold and 1.9 fold) and the 9th day (28.4 fold and 8.5 fold). The jumping times, weight lost and withdrawal score of rats were significantly higher than that of the control group after 9 d chronic EM 1 treatment. (2) After 9 d of administration with EM 1, the specific binding capacity and mRNA expression of MOR in rat cortex, midbrain and striatum were all decreased compared with those of the control and acute treatment groups, but the K d values were not significantly altered. Conclusion:Endomorphin 1 has the tolerant and dependent potent. For long term chronic treatment, Endomorphin 1 induces downregulation of the binding capacity and mRNA of MOR, which may be related to the dependence development.

Objective: To investigate the analgesic effect and impact of lornoxicam on the expression of plasma IL-6 and IL-10 in patients undergoing upper abdominal surgery.Methods:Sixty patients undergoing upper abdominal surgery were randomly allocated into three groups,morphine group(M,n=20),postoperative lornoxicam group(L,n=20) and preemptive lornoxicam group(P,n=20).For group M the subjects received patient controlled intravenous analgesia(PCIA) with morphine(loading dose 0.05 mg/kg,bolus 1 mg,lockout time 10 min,background dose 0 mg) after the surgery.While in group L,8 mg lornoxiam was administered at the end of the surgery,then the same morphine PCIA scheme as in group M was used in combination with intermittent intravenous lornoxiam(8 mg per injection) at 12,24 and 36 h after the surgery.Except that the first 8 mg lornoxicam was injected 30 min before the operation,the analgesic paradigm of group P was similar to group L.The analgesic effect assessed by VAS at rest,the consumed dosage of morphine,and the adverse effects as nausea and vomiting,were recorded at 4,8,12,24 and 48 h.Furthermore,2 ml of the venous blood was drawn before the induction of anesthesia 2,6,12,and 24 h after the surgery to measure the levels of interleukin 6(IL-6) and interleukin 10(IL-10).Results: During the 48 h observation,the VAS at rest was not statistically significant in the three groups,but more morphine was consumed in group M than in group L and group P.There was no difference among the three groups in the incidence of such adverse effects as nausea or vomiting.The basic levels of IL-6 and IL-10 were too low to be measured.The concentrations of IL-10 and IL-6 reached the peak at 2 and 6 h after surgery respectively,and the level of IL-10 in group M was significantly lower than in groups L and P at 2 h.In contrast,the level of IL-6 in group M was significantly higher than in group L and group P at 6 h,and even higher than in group P at 12 h. Conclusion: Lornoxicam,especially when administered before upper abdominal operation,could significantly decrease the dose of morphine for postoperative analgesia and attenuate the inflammatory cytokine response after surgery.

Objective To evaluate the difference of Doumas′method and 15 commercial serum total protein ( TP ) methods based on EP9-A3.Methods Serum panels were quantified for TP with Doumas′method and measured in parallel with 15 commercial methods.The linear regression analyses were performed, followed by calculating relative deviation and 95%CI between commercial method and Doumas′method at three different medical decision levels (45 g/L, 60 g/L, 80 g/L).We also calculated relative deviation, 95% limit of agreement ( LoA ) and 95% CI based on classical and improved Bland-Altman method at three different medical decision levels.If both the relative deviation and 95%CI were within 5%, we conside red the commercial serum total protein method was comparable to Doumas′method.Results (1) All assays presented high correlation ( r>0.975, P<0.001) with the Doumas′method.All assays showed that the relative deviations and 95%CIs were within the biological total error goal (5%) at medical decision levels based on regression analysis.(2) Based on classical and improved Bland-Altman method, fourteen of 15 commercial methods showed that the relative deviations and 95%CIs were within +/-5%. Conclusions All commercial assays are comparable to Doumas′method at medical deviation levels.There is no difference between regression analysis and Bland-Altman method for comparison study.

Objective To investigate the current status of cytotoxicity and mechanical properties of the prosthetic liner on the market in China.Methods Six kinds of liner were collected, namely domestic 6 mm thick foam liner (A), domestic 5 mm thick EVA foam liner (B), German 5 mm thick EVA foam liner (C), Germany 12 mm thick PE foam liner (D), Iceland 3 mm thick silicone liner (E) and Germany 4 mm thick gel liner (F). Microscopic observation and thiazole blue colorimetry were used to detect the cytotoxicity. The content of small organic molecules was determined by the consumption of potassium permanganate. The tensile strength, elongation at break (%), and 100% tensile strength of the prosthetic liner were tested by material mechanics testing machine. The hardness was tested using the Shore hardness tester oo type.Results The cytotoxicity was grade 2 for prosthetic liners A, B, C and D, and was grade 0 for E and F. The redox substance content of prosthetic liners A、B、C exceeded 150 mg/kg. Except the prosthetic liner C, the hardness of the other products were all ≤ 70 HA. Except prosthetic liner D, the tensile strengths were > 1 MPa, breaking elongations were > 120.0%, 100% tensile strengths were > 0.9 MPa for other products.Conclusion Due to materials and production processes, the cytotoxicity and mechanical properties of the six samples are quite different.