Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-D-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D(1) and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.     

Investigation on radiofrequency and laser (980 nm) effects after endoluminal treatment of saphenous vein insufficiency in an ex-vivo model.

OBJECTIVES: An ex-vivo model for the experimental evaluation of endoluminal thermal procedures for occlusion of saphenous veins was developed. Radiofrequency obliteration (RFO) and endovenous laser therapy (ELT) were compared using this model. DESIGN: Experimental ex-vivo treatment study. MATERIALS AND METHODS: The model consists of the subcutaneous foot veins from freshly slaughtered cows which were reperfused in situ with heparinised bovine blood. The veins were treated with either radiofrequency (RFO n=5) or with endoluminal 980 nm laser light (ELT n=5) using a continuous pull-back for RFO and a stepwise illumination and pull-back protocol for ELT. Immediately after treatment perivenous tissue and veins were examined macroscopically. In a second study the same treatment parameters were used in four further vein segments with RFO (n=2) and ELT (n=2). These vein segments were examined microscopically in HE-stained histological sections. RESULTS: Induration of the vessel wall and contraction of the vessel lumen were observed after RFO. Laser treatment produced carbonised lesions of the vein wall. After 12-24 laser exposures these lesions often became transmural, causing complete perforation of the vessel wall. Histological evaluation after radiofrequency treatment demonstrated homogenous circular thermal tissue alteration with disintegration of intima and media structures. Histological evaluation after endovenous laser treatment showed large variations of thermal tissue effects. Tissue effects ranged from major tissue ablation and vessel wall disruption to minor effects located between laser exposures and on the opposite vessel wall. CONCLUSIONS: Our model is suitable for systematic scientific evaluation of endovenous thermal occlusion procedures. Our first results and theoretical considerations indicate that endovenous laser treatment should be modified in order to ensure controlled homogenous circular thermal damage, avoiding vessel wall perforation and damage to perivascular structures.     

Effect of treatments on the progression of COPD: report of a workshop held in Leuven, 11-12 March 2004

During the last decade several long term studies of interventions in patients with COPD have been published. This review analyses the potential of these interventions to alter the progression of the condition. The only treatment that has unequivocally been shown to reduce the rate of decline in FEV(1) is smoking cessation. Active psychological intervention in combination with pharmacotherapy is required. Other treatments may have an effect on the rate of decline in FEV(1) but this appears to be very small, at most. Several treatments affect the exacerbation rate and therefore might affect the progression of the disease. Further studies are warranted to examine this effect.     

Use of cellular and cordless telephones and risk of testicular cancer

A case-control study on testicular cancer included use of cellular and cordless telephones. The results were based on answers from 542 (92%) cases with seminoma, 346 (89%) with non-seminoma, and 870 (89%) controls. Regarding seminoma the use of analog cellular phones gave odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.9-1.6, digital phones OR = 1.3, CI = 0.9-1.8, and cordless phones OR = 1.1, CI = 0.8-1.5. The corresponding results for non-seminoma were OR = 0.7, CI = 0.5-1.1, OR = 0.9, CI = 0.6-1.4, and OR = 1.0, CI = 0.7-1.4, respectively. There was no dose-response effect and OR did not increase with latency time. No association was found with place of keeping the mobile phone during standby, such as trousers pocket. Cryptorchidism was associated both with seminoma (OR = 4.2, CI = 2.7-6.5) and non-seminoma (OR = 3.3, CI = 2.0-5.6), but no interaction was found with the use of cellular or cordless telephones.     

Detection rates of cancer, high grade PIN and atypical lesions suspicious for cancer in the European Randomized Study of Screening for Prostate Cancer

The aim of the studyThis article presents the incidence of prostate cancer, isolated high grade prostatic intraepithelial neoplasia (PIN) and atypical lesions suspicious for prostate cancer (LSPC) during subsequent screening rounds in the centres of five of the countries participating in the European Randomized Study of Screening for Prostate Cancer (ERSPC). The incidence and predictive value of high grade PIN and LSPC for prostate cancer in subsequent biopsy following these diagnoses were evaluated.Patients and methodsStudy group consisted of 56,653 screened men in the ERSPC centres of Finland, Italy, Netherlands, Sweden and Switzerland, who underwent 3–7 screening rounds at 2–4 year interval. Data for prostate cancer were obtained from the ERSPC central database. Data for high grade PIN and LSPC were gathered from each ERSPC centre. Detection rates of subsequent prostate cancer in the first re-biopsy after these diagnoses were determined.ResultsThe average cancer detection rate was 3.5%, 3.2% and 3.5% for the completed rounds 1, 2 and 3, respectively, in all five centres. Incidence of high grade PIN increased from 1.5% in the first round to 5.0% in the third round, varying among centres in the first round between 0.8% and 7.6%. The cancer detection rate in the first re-biopsy after the diagnosis of high grade PIN was 12.9%. Incidence of LSPC was 2.4%, 2.7%, 2.2% and 2.6% in the first, second, third and fourth round, respectively. The cancer detection rate at the first re-biopsy after the diagnosis of LSPC was in average 33.8%.ConclusionsCancer detection rate was stable during the three screening rounds. The wide variation in frequency in particular of high grade PIN among the ERSPC centres suggests a considerable inter-observer variation. The average comparatively low detection rate of isolated high grade PIN in the first screening round may be screening-related, while its consistent increase during three screening rounds could be the consequence of a.o. previous screening and ageing of the population. The observed low risk of prostate cancer after isolated high grade PIN in this screening setting is in line with the current recommendation to abstain from early repeat biopsies after this diagnosis. The association of LSPC with high incidence of prostate cancer in re-biopsies confirms the need for early repeat biopsies and follow-up of these men. The low percentage of LSPC (<3% of biopsies) throughout all rounds is reassuring as it limits the biopsy burden in a screening setting.     

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass

Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.