The effects of taurine on pharmacologically induced myotonia

Taurine reduces the excitability of striated muscle fibers by increasing the membrane conductance to chloride ions (GCl). This action was tested on rats made myotonic by drugs that block GCl by different mechanisms. Experiments were made "in vivo" using electromyographic (EMG) recordings and "in vitro" with intracellular microelectrode recordings from extensor digitorum longus muscle fibers. Taurine did not antagonize the myotonic discharges produced in vivo by anthracene-9-carboxylic acid, nor did it restore GCl lowered in vitro by this agent. However, when myotonia was chronically induced by 20,25 diazacholesterol, taurine given chronically in vivo or acutely in vitro antagonized the EMG myotonia as well as the reduced GCl and increased excitability of single fibers. We conclude that taurine acts directly on chloride channels to modify their kinetics. Our findings suggest that further clinical studies on the use of taurine in muscle disease involving abnormal excitability or chloride channel function will be useful.     

Late-onset mitochondrial disorder with electromyographic evidence of myotonia

We describe a patient with chronic progressive external ophthalmoplegia (CPEO) due to a deletion of mitochondrial DNA (mtDNA) who had electromyographic evidence of myotonic discharges. Myotonia has not previously been described in association with mitochondrial disease and this report extends the known phenotypic expression of these disorders.     

Antagonistic effects of taurine and 4-aminopyridine on guinea pig ileum

The effects of 4-aminopyridine (4-AP) and of taurine on the guinea pig ileum were examined. Four-AP increases the basal activity from 1.3 to 6.45 cm2/min. This effect is atropine-sensitive and calcium-dependent. Taurine counteracts the effects of 4-AP on muscle contracture in a concentration-dependent manner. In muscles preincubated with 20 mM taurine, the effect of 4-AP decreased about 65%. Taurine added at the time of maximal effect of 4-AP reduced the muscle contracture induced by the drug to the basal levels. Glycine and beta-alanine did not influence the contracture induced by 4-AP, whereas 25 mM gamma-aminobutyric acid (GABA) reduced it by 30%. Taurine reduced the basal muscle activity by 50% but did not affect the contracture induced by exogenously applied acetylcholine.     

Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy

The success of botulinum toxin (BT) injections for treatment of cervical dystonia depends on precise identification of dystonic muscles and on quantification of their dystonic involvement. Conventionally, this is attempted by clinical examination analysing the dystonic head position. In this presentation, a more systematic approach is sought by using an electromyography (EMG)-based evaluation procedure. In 10 consecutive patients with cervical dystonia not previously exposed to BT clinical examination, analysing the dystonic head position was performed to classify patients into four groups with similar dystonic head positions. Additionally, a 2-channel concentric needle EMG was used to measure the amplitudes of dystonic and maximal voluntary activities in sternocleidomastoid (SCM), splenius capitis (SC) and trapezius/semispinalis capitis (T/SS) muscles bilaterally. The ratio between both amplitudes, the dystonia ratio, was used to quantify dystonic muscle involvement. In all patients dystonia ratios could be calculated. In patients with similar head positions, EMG evaluation revealed different qualitative and quantitative dystonic involvement patterns. In six patients, there were discrepancies in identification of dystonic muscles between clinical examination and EMG evaluation. EMG evaluation excluded dystonic involvement in five patients. All excluded muscles were SCM. In one of these patients, additional T/SS involvement was detected by EMG evaluation. In one patient, SC involvement was revealed by EMG evaluation. All dystonic muscle involvement detected by EMG evaluation represented genuine dystonic muscle coactivation rather than compensatory muscle activity. The EMG evaluation presented allows quantitative and qualitative identification of dystonic muscle involvement which cannot be achieved by clinical examination. Both pieces of information may be helpful for optimization of BT therapy.     

Electromyographic evaluation of the sound and involved side during gait of spastic hemiplegic children with cerebral palsy

The purpose of this study was to investigate the surface electromyogram (EMG) of the lower limbs of hemiplegic children with spastic cerebral palsy during gait. The EMG of seven muscles was analyzed for 17 children (5-12 years old). The EMG of the involved side was decreased for the examined shank muscles and increased for the hamstrings, during certain phases of the gait cycle, compared with the sound side. The rectus femoris of the involved side showed prolonged activation during the swing phase. The enhanced activation of the hamstrings may be beneficial/compensatory, preventing knee hyperextension. The presence of equinus foot obstructs the foot clearance and hence the prolonged rectus femoris EMG activity during the swing phase may contribute to shorten the lower limb by flexing the hip. Possible compensatory mechanisms of the proximal muscles of the involved lower limb that can be measured with instrumented gait analysis should be taken into account before the decision for a specific treatment.     

Is taurine a hypothalamic neurotransmitter?: a model of the differential uptake and compartmentalization of taurine by neuronal and glial cell particles from the rat hypothalamus

Although taurine has been postulated to be a neurotransmitter or neuromodulator in the mammalian CNS, little is known concerning its role in brain function. Evidence suggesting that taurine may influence endocrine and homeostatic mechanisms via the hypothalamus resulted in our investigations into its function in this brain region.The main objectives of the research were to characterize the specific binding, uptake, and release of taurine in the hypothalamus. A specific aim was to examine the proposed neurotransmitter role for taurine in the hypothalamus. This was accomplished by comparing the characteristics and properties of the binding, uptake, and release of taurine with those for the classical neurotransmitters which satisfy the criteria for a neurotransmitter. On such a comparative basis, the characteristics of taurine uptake satisfy the neurotransmitter criterion of inactivation of taurine in the hypothalamus. However, the observed characteristics of taurine binding and release in the hypothalamus do not satisfy the respective neurotransmitter criteria of specific receptors and Ca²⁺-dependent evoked release. Therefore, solely on the basis of the experimental observations reported herein, we must conclude that taurine apparently does not function as a neurotransmitter in the hypothalamus.Two uptake systems were found in the P₂ fraction, a high affinity uptake system and a low affinity uptake system. Uptake systems for taurine have previously been reported in glial and nerve cell homogenates, and therefore, because of the known contamination of crude synaptosomal preparations with glial particles, we sought to determine the cellular origin of the two taurine uptake systems in our crude preparation. Using a variety of diverse biochemical techniques such as hypo-osmotic shock, release experiments and Arrhenius plots, we determined that physical changes of the media or depolarizing stimuli which would influence neuronal and glial cell particles differently, also had differing effects on high and low affinity taurine uptake or its release from the respective uptake compartments. We conclude that the high affinity taurine uptake system/compartment is located on/in neuronal membranes/particles and that the low affinity taurine uptake system/compartment is located on/in glial membranes/particles. Such a model for the differential cellular transport and compartmentalization of taurine into neuronal and glial cells has important implications concerning its possible role in the CNS.     

Fenoterol precipitating myotonia in a minimally affected case of recessive myotonia congenita

Summary Fenoterol is used in patients with premature labor to delay delivery. A young woman treated with fenoterol developed severe generalized myotonia. Symptoms disappeared after medication had been stopped. In a later study myotonic discharges were found electromyographically in the muscles of the patient and her brother. Both suffered from subclinical recessive myotonia congenita (Becker). A heterozygous manifestation may be supposed.

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Zusammenfassung Fenoterol (Partusisten^®) wird als wehenhemmendes Mittel verwendet. Bei einer jungen Frau trat unter Fenoterol eine schwere generalisierte Myotonie auf, die nach Absetzen des Medikamentes wieder verschwand. Bei der Patientin und bei ihrem Bruder fand sich später elektromyographisch eine subklinische Myotonie. Wahrscheinlich sind beide Geschwister heterozygote Genträger der rezessiven generalisierten Myotonie (Becker).

     

Intracellular studies of GABA and taurine action on the neurons of the cat sensorimotor cortex.

The action of taurine and GABA on the cat cerebral cortex neurons was studied. Electrophoretically administered taurine and GABA hyperpolarized the neuron membrane. GABA, in contrast to taurine, sharply increased the somatic membrane conductance. Taurine action was weaker than that of GABA and its effects were not always observed. However, in a number of instances it exerted inhibitory influence similar to GABA action. Some facts make it possible to suppose that taurine acts mainly on the neuron dendrites. The data obtained are in accordance with the supposition that taurine might be an inhibitory transmitter in the cerebral cortex.     

Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons.

Glutamate-induced excitotoxicity has been implicated as an important mechanism underlying a variety of brain injuries and neurodegenerative diseases. Previously we have shown that taurine has protective effects against glutamate-induced neuronal injury in cultured neurons. Here we propose that the primary underlying mechanism of the neuroprotective function of taurine is due to its action in preventing or reducing glutamate-induced elevation of intracellular free calcium, [Ca(2+)](i). This hypothesis is supported by the following findings. First, taurine transport inhibitors, e.g., guanidinoethyl sulfonate and beta-alanine, have no effect on taurine's neuroprotective function, suggesting that taurine protects against glutamate-induced neuronal damage through its action on the extracellular membranes. Second, glutamate-induced elevation of [Ca(2+)](i) is reduced to the basal level upon addition of taurine. Third, pretreatment of cultured neurons with taurine prevents or greatly suppresses the elevation of [Ca(2+)](i) induced by glutamate. Furthermore, taurine was found to inhibit the influx but not the efflux of (45)Ca(2+) in cultured neurons. Taurine has little effect on the binding of [(3)H]glutamate to the agonist binding site and of [(3)H]MDL 105,519 to the glycine binding site of the N-methyl-D-aspartic acid receptors, suggesting that taurine inhibits (45)Ca(2+) influx through other mechanisms, including its inhibitory effect on the reverse mode of the Na(+)/Ca(2+) exchangers (Wu et al. [2000] In: Taurine 4: taurine and excitable tissues. New York: Kluwer Academic/Plenum Publishers. p 35-44) rather than serving as an antagonist to the N-methyl-D-aspartic acid receptors.     

不同起病部位的ALS病人异常肌电区域分布研究

目的 :探讨不同起病部位的ALS病人在 4个下运动神经元支配区域异常肌电的分布情况。方法 :对 10 2例临床诊断为ALS的病人分别行 4组下运动神经元区域 (脑干 ,颈 ,胸 ,腰骶髓 )的针极肌电图检查。对 87例同时进行了胸锁乳突肌的检查。结果 :4组肌电检查区域的结果示 :颈段与胸段异常率在各起病组中最高 ,脑干及腰骶段在各组中异常率不同 (差异有显著意义 ,P <0 0 5 ) ;胸锁乳突肌上、下肢起病组的异常率均高于同组的脑干支配肌。结论 :在ALS病人中 ,异常肌电的分布与起病部位有关。不论哪一部位起病 ,4个区域均可受累 ,因此必须全都检查。胸锁乳突肌具有特殊的诊断及鉴别诊断价值     

Protective effect of taurine on the light-induced disruption of isolated frog rod outer segments

Isolated frog rod outer segments (ROS) incubated in a Krebs-bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light-induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5–25 mM, effectively counteracts the light-induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS.     

Electrophysiological analysis of taurine and glycine action on neurons of the mudpuppy retina. I. Intracellular recording

Intracellular recordings were carried out in the perfused retina-eyecup preparation of the mudpuppy. Taurine and glycine were added to the bathing medium to study their effects on different retinal neurons. In a few cases, γ-aminobutyric acid was exogenously applied to compare GABA vs taurine/glycine action. Receptors and horizontal cells were relatively insensitive to taurine/glycine, while amacrines and ganglion cells were comparatively more sensitive to these agents. Bipolar cells proved to be differentially effected by inhibitory amino acids: hyperpolarizing (OFF) bipolars were depressed by taurine/glycine and proved less sensitive to GABA; depolarizing (ON) bipolars were suppressed by GABA and were comparatively less sensitive to glycine/taurine. Taurine and glycine had identical actions on neurons and both were about equally effective at the same concentration. Strychnine blocked the action of taurine and glycine. The patterns of glycine/taurine sensitivity and their effects on second order neurons eliminate taurine as a photoreceptor transmitter; one or both of these agents may be utilized by a subclass of amacrine cells which interact with hyperpolarizing bipolars, other amacrine cells and ganglion cells. It appears that taurine or glycine or both may be selectively involved in OFF channel activity, while GABA may subserve an equivalent role for the ON channel.     

Regulatory role of cystein dioxygenase in cerebral biosynthesis of taurine. analysis using cerebellum from 3-acetylpyridine-treated rat

The effect of 3-acetylpyridine (3-AP) administration on the biosynthesis of taurine in the rat brain has been studied. Treatment with 3-AP induced a significant decrease in the cerebellar contents of taurine and its metabolic precursors, cysteine sulfinic acid (CSA) and cysteic acid (CA), as well as a selective degeneration of climbing fibers in the molecular layer of the cerebellum. It was found that the activity of cerebral cysteine dioxygenase, the enzyme catalyzing the formation of CSA from cysteine, consisted of two systems with low and high Km values. The 3-AP-induced attenuation of cysteine dioxygenase activity with a low Km value was noted only in the cerebellum, while that with a high Km value was detected not only in the cerebellum but also in other brain areas such as the medulla oblongata, striatum and cerebral cortex. In contrast, no alteration in the activity of cysteine sulfinic acid decarboxylase (CSD) was observed in any brain areas examined following the administration of 3-AP. Furthermore, it was found that essentially no cystamine as well as a very low activity of cysteamine dioxygenase is present in the brain. The present results suggest that taurine in the brain is synthesized from cysteine, mainly by the CSA and CA pathways, and the observed decline of cerebellar taurine in 3-AP-treated rats may be due to an attenuation of the biosynthesis, possibly at the step of cysteine dioxygenase. A possible regulatory role of cysteine dioxygenase with a low Km value in the biosynthesis of cerebral taurine is also suggested.     

The quantification of myotonia. A problem in the evaluation of new antimyotonic drugs

The evaluation of an antimyotonic drug is often difficult since the severity of myotonia is itself hard to assess. The rise in arterial potassium level produced by the infusion of increasing concentrations of potassium chloride brought about reproducible changes in the excitability level of myotonic muscles proportional to the plasma potassium concentration. The excitability changes were assessed by three methods commonly used for evaluating antimyotonic drugs. The duration of the electromyographic relaxation time after maximal voluntary effort proved to be the only test which reliably assessed the variations of muscular excitability proportional to the increased plasma potassium. By contrast, the duration of percussion- or electrically-induced myotonic after-discharges was extremely variable and independent of plasma potassium.     

Narrative Therapy vs. Cognitive-Behavioral Therapy for moderate depression: Empirical evidence from a controlled clinical trial

Abstract

Background: Systematic studies of the efficacy of Narrative Therapy (NT) for depression are sparse. Objective: To evaluate the efficacy of individual NT for moderate depression in adults compared to Cognitive-Behavioral Therapy (CBT). Method: Sixty-three depressed clients were assigned to either NT or CBT. The Beck Depression Inventory-II (BDI-II) and Outcome Questionnaire-45.2 (OQ-45.2) were used as outcome measures. Results: We found a significant symptomatic reduction in both treatments. Group differences favoring CBT were found on the BDI-II, but not on the OQ-45.2. Conclusions: Pre- to post-treatment effect sizes for completers in both groups were superior to benchmarked waiting-list control groups.     

Monopolar needle evaluation of paraspinal musculature in the cervical,thoracic, and lumbar regions and the effects of aging

Motor unit characteristics (Phases, turns, amplitude, duration, and area) were measured using a monopolar needle and narrowed bandpass (500 Hz to 10 kHz) in cervical, thoracic, and lumbar paraspinal muscles in 66 subjects (36 women and 30 men) aged 22-81 years (mean age 45.7 years). Cervical motor units were of lower amplitude and area than thoracic and lumbar motor units (P = 0.0001), respectively. The durations of lumbar motor units were longer and larger than cervical and thoracic motor units (P = 0.0004). Analysis of covariance of the measured characteristics against age showed no significance in the cervical and thoracic regions. In lumbar paraspinal motor units, phases and turns increased significantly with age (P = 0.044 and P = 0.016, respectively). The increase was < 1.0 phase over 30 years. Motor unit amplitude increased with aging (P = 0.055) showing an increase of 360 μV over a 30-year time period. It is appropriate to assess the number of phases and turns, as well as the duration of the motor units in the cervical and thoracic (but not lumbar) spines in addition to seeking evidence of spontaneous, single fiber discharges.© 1995 John Wiley &Sons, Inc.     

Electrophysiological analysis of taurine and glycine action on neurons of the mudpuppy retina. II. ERG, PNR and Müller cell recordings

Extracellular electrophysiological recordings of the electroretinogram (ERG) and proximal negative response (PNR) were carried out in the perfused retina-eyecup preparation of the mudpuppy. Intracellular recordings were obtained from Müller cells. Bath-applied taurine/glycine had identical effects on the ERG, PNR and Müller cell responses and the effects of both agents were blocked by strychnine. Taurine and glycine suppressed the d-wave of the ERG, the OFF response of Müller cells and ON and OFF responses of the PNR. These observations show that taurine/glycine sensitivity is predominantly found in the OFF channel of the ERG whose underlying neuronal basis appears to be dark evoked depolarization of OFF bipolars.     

Electrophysiological evaluation of pharyngeal phase of swallowing in patients with Parkinson's disease.

We studied the various physiological aspects of oropharyngeal swallowing in Parkinson's disease (PD). Fifty-eight patients with PD were investigated by clinical and electrophysiological methods that measured the oropharyngeal phase of swallowing. All patients except 1 had mild to moderate degree of disability score. Dysphagia was demonstrated in 53% of all patients in whom the test of dysphagia limit was abnormal. All PD patients with or without dysphagia displayed the following abnormalities: (1) the triggering of the swallowing reflex was prolonged probably due to inadequate bolus control in the mouth and tongue and/or a specific delay in the execution of the swallowing reflex; (2) the duration of the pharyngeal reflex time was extremely prolonged due to slowness of the sequential muscle movements, especially those of the suprahyoid-submental muscles; (3) cricopharyngeal muscle of the upper oesophageal sphincter was found to be electrophysiologically normal; and (4) the electrophysiological phenomena in PD patients could not be strongly correlated with the degree of the disability and clinical score of the PD. It was concluded that various motor disorders of PD have considerable influence on oropharyngeal swallowing: hypokinesia, reduced rate of spontaneous swallowing, and the slowness of segmented but coordinated sequential movements rather than any abnormalities in the central pattern generator of the bulbar center. Some compensatory mechanisms in the course of PD may explain the benign nature of swallowing disorder until the terminal stage of the disease. Similarly, the swallowing problems of PD are not only related with the dopamine deficiency; some other nondopaminergic mechanisms may also be involved.