僵人综合征4例分析及文献回顾

目的 总结僵人综合征的临床特点,提高对该病的认识和诊断水平.方法 分析4例病例,总结其临床表现、典型的肌电图表现及治疗效果.结果 4例患者3名男性,1名女性,年龄29岁～51岁,1例为受凉约2w后出现症状,3例无明显诱发因素.4例既往均无特殊疾病史,亦无家族同类病史.2例为亚急性起病,2例为慢性起病,病程分别为1～13个月.主要表现为躯干、四肢近端肌肉出现阵发或持续性僵硬和疼痛,从而引起相应部位的运动障碍.4例均行常规肌电图检查,显示在放松状态下时有持续运动单位电位,应用安定后消失.经苯二氮草类、巴氯芬治疗后2例可痊愈,另2例亦无反复发作及恶化.结论 僵人综合征是一种罕见的肌肉疾病,易误诊,苯二氮草类、巴氯芬治疗可获良好效果.     

食管多通道腔内阻抗技术联合pH监测对嗳气症发病机制及治疗的研究

目的探讨食管多通道腔内阻抗技术联合pH检测对嗳气症各亚型的发病机制及临床疗效。方法以我院2009年8月至2011年8月治疗的128例嗳气症患者为研究对象,使用食管多通道腔内阻抗技术联合pH检测进行检测,对嗳气患者各亚型的发病机制、与胃食管反流的关系等进行研究;使用巴氯芬对研究对象进行治疗,并进行各亚型之间的疗效比较,并对相关数据进行统计学分析。结果通过食管多通道腔内阻抗联合pH监测发现:①吞气症和非特异性嗳气综合征的发病机制不同,吞气症的嗳气是由气体吞咽后,且所吞咽的气体并未进入胃内而引发症状,非特异性嗳气综合征则是由胃内引发,且不伴有吞咽;②胃食管反流与嗳气发生的时间具有相关性,吞气症可能是由于瞬间下食管括约肌的松弛导致嗳气和反流同时发生,非特异性嗳气综合征可能是嗳气发生后由于LES的松弛导致反流的发生;③使用巴氯芬治疗,非特异性嗳气综合征的疗效优于吞气症,差异具有统计学意义(P>0.05)。结论嗳气症各型的发病机制不同,直接导致使用巴氯芬治疗的效果存在差异性;胃食管炎与嗳气症存在时间相关性,吞气症可能是由于瞬间下食管括约肌的松弛导致嗳气和反流同时发生,非特异性嗳气综合征可能是嗳气发生后由于LES的松弛导致反流的发生。     

老年腹膜透析患者巴氯芬药物中毒催醒治疗与护理

巴氯芬是一种高效的作用在脊髓部位的肌肉松弛剂,其作用机制和药理学特性均与其他肌肉松弛剂不同。人体中枢神经系统主要抑制性递质氨基丁酸（GABA）的衍生物,通过抑制脊髓的单突触反射和多突触反射的传递,刺激GABAB受体,从而抑制兴奋性神经递质的释放,可作用于脊髓上端而产生中枢神经抑制作用。     

GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons. OBJECTIVE: The objective of these experiments was to examine the role of GABA manipulations in the PPTg on nicotine self-administration. METHODS AND RESULTS: Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the GABA agonists muscimol (10-50 ng) and baclofen (30-60 ng) reduced nicotine self-administration maintained on a fixed-ratio schedule of reinforcement (30 microg/kg per infusion); self-administration of cocaine (0.3 mg/kg per infusion) under an identical schedule was not affected. Muscimol and baclofen were also examined after intra-PPTg microinfusion in animals trained to self-administer nicotine on a progressive-ratio schedule (10 and 30 microg/kg per infusion). Progressive-ratio responding was sensitive to pharmacological manipulations such as a change in the nicotine dose available for self-administration, or intra-PPTg microinfusion of the nicotinic antagonist dihydro-beta-erythroidine (30 microg). However, nicotine self-administration on a progressive-ratio schedule was not altered by intra-PPTg microinfusions of GABA agonists. CONCLUSIONS: These data confirm that the PPTg is involved in nicotine self-administration, a conclusion that is independent of the schedule of reinforcement that is used. GABAergic mechanisms in the PPTg play a selective role in nicotine reinforcement compared to cocaine, and that role is restricted to the characteristics of reinforcement measured by fixed-ratio responding.     

Distribution and depression of the GABAB receptor in the spinal dorsal horn of adult rat

γ-Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in vertebrate nervous system. The metabotropic receptor for GABA, GABA_B receptor, is characterized as a G protein-coupled receptor subtype. In the present study, GABA_B receptor-like immunoreactivity (GABA_BR-LI) in the rat spinal cord and dorsal root ganglion (DRG), as well as GABA_B receptor-mediated depression in the spinal dorsal horn were examined by using immunohistochemistry and whole-cell voltage-clamp recording technique, respectively. Under light microscope, GABA_BR-LI was densely found in laminae I and II of the dorsal horn. DRG cells of various diameters also showed GABA_BR-LI. Electron microscopy further revealed that GABA_BR-LI was also localized in terminals of myelinated, unmyelinated fibers as well as the somatodendritic sites of dorsal horn neurons. Bath application of a GABA_B receptor agonist, baclofen (10 μM, 30 s), induced a slow outward (inhibitory) current in dorsal horn neurons. This slow current was depressed when the postsynaptic G protein-coupled receptor was inhibited, indicating the postsynaptic action of baclofen. Under the condition of postsynaptic GABA_B receptor being inhibited, baclofen (10 μM, 60 s) depressed large (Aβ) and fine (C, Aδ) afferent fiber-evoked monosynaptic excitatory postsynaptic currents, indicating presynaptic inhibition of GABA_B receptor on elicited neurotransmitter release. Taken together, the results suggest that baclofen-sensitive GABA_B receptor is expressed pre- and postsynaptically on primary afferent fibers and neurons in the spinal dorsal horn; activation of GABA_B receptor in the dorsal horn postsynaptically hyperpolarizes dorsal horn neurons and presynaptically inhibits primary afferents.     

Modulation by adenosine of a neuronal inhibitory interaction in the rat hippocampus

Adenosine is acknowledged to have a primarily inhibitory function in the central nervous system, but is believed to have little effect on inhibitory neurones themselves. It is however, difficult to determine the effect of adenosine on inhibitory synaptic potentials since adenosine directly depresses evoked potentials and, in the presence of bicuculline to block GABA_A-mediated inhibition, the bicuculline-resistant fraction of paired-pulse inhibition (ppi) is greater between pairs of small potentials than between pairs of larger potentials. Here, adenosine increased bicuculline-resistant ppi when stimulus strength was constant between adenosine and control but ppi of responses in adenosine was markedly less than ppi of control responses of the same size. Adenosine had less effect on the size of ‘conditioned’ potentials than on control potentials. It is concluded that adenosine can reduce the bicuculline-resistant fraction of paired-pulse inhibition in the hippocampus. Further quantitative comparison of the effects of adenosine on ppi and on single evoked potentials excluded a difference in the potency of adenosine at excitatory and inhibitory terminals as an explanation for this activity. The results suggest that adenosine may diminish bicuculline-resistant paired-pulse inhibition by enhancing a simultaneous facilitatory component of the neuronal responses.     

Involvement of the amygdaloid complex in neuromodulatory influences on memory storage

Neuromodulatory systems activated by training experiences appear to play a role in influencing memory storage processes. The research summarized in this paper examined the effects, on memory, of posttraining administration of treatments affecting adrenergic, opioid peptidergic and GABAergic systems. When administered after training, drugs affecting these systems all produce dose- and time-dependent effects on memory storage. The drug effects on memory are blocked by lesions of the amygdaloid complex as well as lesions of the stria terminalis, a major amygdala pathway. The effects of drugs affecting these neuromodulatory systems are also blocked by injections of beta-adrenergic antagonists administered to the amygdaloid complex. Thus, the findings suggest that the neuromodulatory systems affect memory storage through influences involving the activation of beta-adrenergic receptors within the amygdala. These findings are consistent with the view that the amygdala is involved in regulating the storage of memory in other brain regions.     

Bay K 8644 induces a reversible spasticity-like syndrome in rats

The dihydropyridine Bay K 8644 exerts a positive modulation of Ca²⁺ channels. Administration of Bay K 8644 3–5 mg/kg i.p. to rats induces within 15 min a severe spasticity syndrome consisting of stiff tail, arched back, stretching and twisting of forelimbs and hindlegs and backwards motility and rolling over. The syndrome was effectively antagonized by nifedipine 3–30 mg/kg but not by the other Ca²⁺ channel blockers flunarizine, diltiazem and verapamil. Diltiazem even enhanced the spasticity. Diazepam 10–30 mg/kg i.p. completely blocked the spasticity whereas the other muscle relaxants (−)-baclofen and the β-carboline ZK 93423 were completely inactive. These findings with Bay K 8644 suggest that spasticity may be caused by changed Ca²⁺ homeostasis.     

Evidence of a specialized transport mechanism for the intestinal absorption of baclofen

Absorption of the spasmolytic drug baclofen in three selected intestinal segments of living anaesthetized rats in situ, is shown to be a specialized transport mechanism obeying Michaelis-Menten kinetics. Equation parameters were calculated through different procedures, whose features are discussed. A computer method based on the integrated form of Michaelis-Menten equation which reproduces the entire time course of drug absorption from the data found in three intestinal perfusion series at different initial concentrations, yielded Vm and Km values of 12.0 mg h-1 and 8.0 mg, respectively, in the mean segment of the small intestine, a rather selective absorption site for baclofen. Lesser but comparable absorption rates were found in the proximal and distal segments of the small intestine, whereas in colon, drug absorption was negligible. Baclofen transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. If these results were extrapolated to humans, they would explain the excellent bioavailability profiles reported for baclofen at normal doses in spite of its physicochemical properties, which do not favour passive diffusion. Based on the same principle, the administration of usual doses at shorter time intervals could be recommended, instead of high, when higher plasma levels at steady-state are needed. On the other hand, more than 8-h sustained-release preparations of baclofen should, probably, be avoided.     

Effects of GABAB activation and inhibition on vestibulo-ocular and optokinetic responses in the pigmented rat

The effects of the GABA_B agonist baclofen and the GABA_B antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABA_B receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABA_B receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceletory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.