两种不同麻醉和镇痛方法对糖耐量减低的老年高血压患者全膝置换术后糖代谢的影响

目的两种不同麻醉和镇痛方法对糖耐量减低的老年患者全膝置换术后糖代谢的影响。方法60例择期行全膝置换术的糖耐量减低患者随机分成腰硬联合麻醉联合术后硬膜外镇痛组（腰硬组）和全身麻醉联合术后静脉镇痛组（全麻组）各30例,分别测定入手术室后,术后30min、1、3、7d的空腹血糖和胰岛素浓度;术后10d空腹和口服糖耐量试验（OGTT）2h的血糖和胰岛素浓度,并计算相应胰岛素抵抗指数,以视觉模糊疼痛评分（VAS）评估术后1h、1、3、7d的疼痛评分,并记录围手术期相关不良事件发生率。结果腰硬组术后30min、1、3d的空腹血糖相比全麻组明显较低（均P＜0.05）;腰硬组在术后30min、1、3、7d的胰岛素浓度和胰岛素抵抗指数相比全麻组明显较低（均P＜0.05）。腰硬组在术后1d和3d的中餐后2h血糖浓度相比全麻组明显较低（均P＜0.05）。全麻组术后10d空腹、OGTT2h的胰岛素浓度和胰岛素抵抗指数相比术前均明显升高（均P＜0.05）,且相比腰硬组明显更高（均P＜0.05）。术后1h和术后1d腰硬组VAS评分明显小于全麻组（均P＜0.05）。结论腰硬联合麻醉和硬膜外镇痛能减轻糖耐量减低的老年高血压患者的全膝置换术后糖代谢紊乱。     

Protein-prime/modified vaccinia virus Ankara vector-boost vaccination overcomes tolerance in high-antigenemic HBV-transgenic mice

BackgroundTherapeutic vaccination is a novel treatment approach for chronic hepatitis B, but only had limited success so far. We hypothesized that optimized vaccination schemes have increased immunogenicity, and aimed at increasing therapeutic hepatitis B vaccine efficacy.MethodsModified Vaccinia virus Ankara (MVA) expressing hepatitis B virus (HBV) antigens was used to boost protein-prime vaccinations in wildtype and HBV-transgenic (HBVtg) mice.ResultsProtein-prime/MVA-boost vaccination was able to overcome HBV-specific tolerance in HBVtg mice with low and medium but not with high antigenemia. HBV-specific antibody titers, CD8+ T-cell frequencies and polyfunctionality inversely correlated with HBV antigen levels. However, optimization of the adjuvant formulation, increasing the level of antigen expression and utilization of HBsAg of heterologous subtype induced HBV-specific CD8+ and CD4+ T-cells and neutralizing antibodies even in high-antigenemic HBVtg mice.ConclusionsOur results indicate that high HBV antigen levels limit the immunological responsiveness to therapeutic vaccination but optimization of the vaccine formulation can overcome tolerance even in the presence of high antigenemia. These findings have important implications for the development of future therapeutic hepatitis B vaccination strategies and potentially also for the stratification of chronic hepatitis B patients for therapeutic vaccination.     

脓毒症病人血液净化联合早期肠内营养的耐受性管理

目的:探讨外科脓毒症病人连续性血液净化(CBP)联合早期肠内营养(EEN)的耐受性管理措施.方法:将入住我科ICU诊断为脓毒症并行床旁CBP治疗的危重症病人239例分为两组.对照组(n=118)病人在生命体征平稳、肠道功能恢复后开始EN治疗;观察组(n=121)病人在入住ICU的24 ～ 48 h即开始给予EEN治疗. 结果:治疗后一周,观察组病人血清清蛋白(ALB)较治疗前明显上升(P＜0.05);总蛋白(TP)、ALB、前清蛋白(PA)显著高于对照组(P＜0.01).观察组病人EEN耐受率达80.12％,入住ICU天数、机械通气时间与对照组比均有显著性差异(P＜0.o1). 结论:脓毒症病人CBP联合EEN的同时采取耐受性管理措施,不仅可保障EEN的安全实施,而且有效地改善病人的营养指标,缩短机械通气和入住ICU时间,有利于加速病人康复.     

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P < 0.05). Nevertheless, this effect decreased about 53% after the chronic treatment (3 doses per day, for 4 days). No pharmacokinetic interaction between metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.     

Harm from others’ drinking: How problematic do people with and without experience of harm perceive it to be?

BackgroundThe aims were (1) to map how problematic people perceive it to be that a person experiences different types of harm from others’ drinking, (2) to describe how problematic victims of harm from others’ drinking perceive the experience to be, and 3) to investigate how perceptions of harm from others’ drinking vary according to demographic characteristics, own drinking and experience of harm.Methods2182 persons in Norway aged 18–69 years participated in a panel web survey in 2013. They responded to questions about six types of harm from others’ drinking.ResultsBoth people with and without experience of harm from others’ drinking perceived it as problematic that someone experiences such harm. Moreover, persons with experience of harm perceived their own experience of harm as less problematic than they perceived it that someone else should experience harm. While people with and without experience of harm from others’ drinking perceive the same types of harm from others’ drinking as least problematic, they differed with regards to which types of harms they perceived as most problematic. Perceptions of harm varied according to demographic characteristics, own drinking and experienced harm.ConclusionThe fact that people both with and without experience of harm from others’ drinking perceived it as problematic that someone experiences such harm may be used as an argument for implementing and/or retaining effective alcohol policy measures. The contrast in perception of experienced harm and how problematic it is that someone else experiences harm suggest that the questions used within this survey tradition may be too general to provide meaningful information about prevalence and severity of experienced harm from others’ drinking. Future research should address this further.     

Effect of ethanol on urine output in rats

Experiments were carried out to delineate the effect of ethanol on urine output in rats. Ethanol (0.75-6.0 g/kg IG) had a dose dependent effect on urine output in hydrated animals. Compared to control animals, moderate (1.50, 2.50 g/kg) doses of ethanol administered intragastrically, increased urine volume during the first hour after treatment and decreased urine osmolality. Large doses of ethanol (4-6 g/kg) decreased urine output and increased urine osmolality (at 1 hr post-treatment) compared to a control group. Treatment of rats with 2.5-5.0 g/kg/day ethanol for 15 days produced tolerance to ethanol diuresis. The degree of tolerance was dose related. Significant tolerance developed with 4 days of 5.0 g/kg ethanol treatment. Loss of tolerance was also rapid. Tolerance to ethanol-induced diuresis was no longer evident 3 days after in rats treated with 5.0 g/kg of ethanol daily for 2 weeks.     

Role of brain catecholamines and 5-hydroxytryptamine in morphine induced temperature changes in normal and tolerant rats and mice

Summary Morphine (5–20 mg/kg) produced hyperthermia in normal, unrestrained rats. Rats which were chronically treated with morphine became tolerant and physically dependent but did not develop tolerance to the acute hyperthermia. Pretreatment of rats with 6-hydroxydopamine to deplete brain catecholamines potentiated the acute morphine hyperthermia in normal rats but not in tolerant rats. The effect is probably related to brain dopamine. Depletion of brain 5-hydroxytryptamine (5-HT) produced by 5,6-dihydroxytryptamine pretreatment, antagonized the acute morphine hyperthermia in both normal and tolerant rats. Morphine (5–20 mg/kg) produced hypothermia in both normal and morphine tolerant mice. Pretreatment of normal mice with 6-hydroxydopamine depleted brain noradrenaline and dopamine and antagonized the hypothermia. Pretreatment with pargyline and 6-hydroxydopamine caused a greater loss of cerebral dopamine than 6-hydroxydopamine alone and resulted in an acute morphine hyperthermia. Morphine also caused hyperthermia when given to tolerant mice pretreated with 6-hydroxydopamine. Pretreatment of normal mice with 5,6-dihydroxytryptamine totally abolished the acute morphine hypothermia. In tolerant mice treated with 5,6-dihydroxytryptamine morphine caused a rise in temperature. It is concluded that (1) a single dose of morphine given to normal rats shifts a hypothalamic 5-HT: dopamine balance in favour of 5-HT; (2) activation of a 5-HT mechanism causes hyperthermia whereas dopamine mediates hypothermia; (3) rats chronically treated with morphine do not become tolerant to the acute hyperthermia because morphine tolerance has little effect on 5-HT; (4) brain dopamine mechanisms readily develop tolerance to morphine; (5) the hypothermia produced by a single dose of morphine in normal mice is mediated by dopamine and, to a lesser extent, 5-HT mechanisms; (6) the hypothermic mechanisms rapidly develop tolerance to morphine; (7) loss of cerebral dopamine and 5-HT in morphine tolerant mice leads to an acute morphine hyperthermia due to another neurotransmitter.     

Effects of heroin and naltrexone on plasma prolactin levels in man

Plasma levels of prolactin were increased following intravenous self-administration of heroin by young men with a history of heroin addiction. Following 10 days of controlled heroin usage, tolerance could be demonstrated to the acute prolactin-releasing effect of heroin. There was no evidence that a single dose of naltrexone affected basal prolactin levels.     

Physical dependence and tolerance development after chronic exposure to low levels of morphine in the rat

A sustained-release delivery system containing ¹⁴C-morphine was implanted subcutaneously in rats. Measurement of urinary excretion of ¹⁴C suggested a steady state release of approximately 640 μg ¹⁴C morphine/day during a 10-day test period. Tolerance developed rapidly to the analgetic effects produced by an injected ED₉₅ dose of morphine sulfate in implanted rats tested on the hot-plate. Physical dependence, determined by naloxone-precipitated abstinence behavior, was evident in rats at 24 hr. Morphine dosage was estimated to be as low as 2.5 mg/kg/day. Peak abstinence behavior was observed on Day 4. However, naloxone-precipitated withdrawal signs were markedly diminished by Day 6 and essentially absent by Day 8. These results are discussed with reference to the suggestion that metabolic changes, occuring during chronic exposure to morphine, may explain the lack of abstinence behavior during a time when maximal concentrations of urinary morphine were observed and a high degree of tolerance was manifest.     

Behavioural tolerance to amphetamine and other psychostimulants: The case for considering behavioural mechanisms

An hypothesis is presented about the nature of behavioural tolerance in animals to stimulant drugs. It is suggested that, in many behavioural procedures, tolerance is due to behavioural adaptation to those drug effects which cause disruption of ongoing rewarded behaviour. This unitary hypothesis accounts for the available data on tolerance and cross-tolerance to stimulants more effectively than all of the other more conventional explanations which are based upon dispositional or functional concepts, the most common of which are described, evaluated, and found to be inadequate. Furthermore, it is suggested that attempts to explain tolerance in terms of changes in synaptic functioning are subject to very considerable problems of interpretation and that an analysis of behavioural mechanisms may be of greater value in understanding the process of behavioural tolerance. Evidence for the basic behavioural hypothesis is outlined in some detail, and a theoretical justification presented for its major assumptions. Operant studies of chronic stimulant effects on behaviour have often produced very complex patterns of data, considerable differences being reported both between subjects and between studies. A speculative model is presented which attempts to account for this pattern of data in tolerance studies.The authors of this paper are arranged alphabetically and should be considered equal contributors