Excitotoxic potential of exogenous ferritin and apoferritin: changes in ambient level of glutamate and synaptic vesicle acidification in brain nerve terminals.

Ferritin, an iron storage protein, is present in the serum and cerebrospinal fluid, has receptors on the cell surface, able to penetrate the brain-blood barrier, can be secreted from the cells, and leaks from destroyed cell in insult and brain trauma. The effect of exogenous ferritin on the key characteristic of glutamatergic neurotransmission was assessed in rat brain nerve terminals (synaptosomes). Exogenous ferritin (80 µg/ml, iron content 0.7%) significantly increased the ambient level of L-[(14)C]glutamate (0.200±0.015 versus 0.368±0.016 nmol/mg of protein) and endogenous glutamate (fluorimetric glutamate dehydrogenase assay) in the nerve terminals. This increase was not a result of augmentation of tonic release because the velocity of tonic release of L-[(14)C]glutamate was not changed significantly in ferritin-treated synaptosomes as compared to the control. Ferritin caused a decrease in synaptic vesicle acidification that was shown using fluorescent dye acridine orange. Iron-dependence of the effects of ferritin was analyzed with apoferritin (0.0025% residual iron). Apoferritin weakly affected the proton electrochemical gradient of synaptic vesicles but increased the ambient level and decreased the initial velocity of uptake of L-[(14)C]glutamate by synaptosomes, nevertheless these effects were ~30% lesser than those caused by ferritin. Exogenous ferritin can provoke the development of excitotoxicity increasing the ambient level of glutamate and lowering synaptic vesicle acidification and glutamate uptake in the nerve terminals, however these effects are not completely iron-dependent. Thus, in the CNS exogenous ferritin can act as a modulator of glutamate homeostasis in iron-dependent and iron-independent manner.

Neuroprotection by lowering cholesterol: a decrease in membrane cholesterol content reduces transporter-mediated glutamate release from brain nerve terminals.

BACKGROUND: In our earlier work, a reduction of cholesterol content increased the extracellular glutamate level in rat brain nerve terminals (synaptosomes) that was a result of the lack of transporter-mediated glutamate uptake. The aim of this study was to assess transporter-mediated release of glutamate from cholesterol-deficient synaptosomes. In stroke, cerebral hypoxia/ischemia, and traumatic brain injury, the development of neurotoxicity is provoked by enhanced extracellular glutamate, which is released from nerve cells mainly by glutamate transporter reversal - a distinctive feature of these pathological states. METHODS: Laser scanning confocal microscopy, spectrofluorimetry, radiolabeled assay, and glutamate dehydrogenase assay. RESULTS: Cholesterol acceptor methyl-ß-cyclodextrin (15mM) reduced the cholesterol content in the synaptosomes by one quarter. Transporter-mediated glutamate release from synaptosomes: 1) stimulated by depolarization of the plasma membrane; 2) by means of heteroexchange with competitive transportable inhibitor of glutamate transporters dl-threo-ß-hydroxyaspartate; 3) in low [Na(+)] medium; and 4) during dissipation of the proton gradient of synaptic vesicles by the protonophore cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP); was decreased under conditions of cholesterol deficiency by ~24, 28, 40, and 17%, respectively. CONCLUSIONS: A decrease in the level of membrane cholesterol attenuated transporter-mediated glutamate release from nerve terminals. Therefore, lowering cholesterol may be used in neuroprotection in stroke, ischemia, and traumatic brain injury which are associated with an increase in glutamate uptake reversal. This data may explain the neuroprotective effects of statins in these pathological states and provide one of the mechanisms of their neuroprotective action. However, beside these disorders, lowering cholesterol may cause harmful consequences by decreasing glutamate uptake in nerve terminals.

[Multiple local involvement of peripheral nerves in workers suffering from occupational hands disorders].

Stimulation and needle electromyography studies covered 102 patients with occupational hands disorders. 87% of the examinees showed tunnel syndromes signs: 44% of those had one tunnel syndrome, 36% - two synromes, and 7% - multiple ones. The results failed to demonstrate reliable difference in tunnel syndrome frequency for vibration exposure and functional hands overstrain. Sensitivity thresholds in vibration disease were increased in 86.7% of the examinees and in 61.5% of those with functional hands overstrain. Peripheral nerve disorders in residual defects with occupational hands diseases are persistent due to compression within physiologic tunnels.

Peripheral neuromotor status in convalescents after tick-borne encephalitis.

Complex electromyographic examinations of 57 patients with different forms of tick-borne encephalitis were carried out during acute and delayed periods. Abnormalities of the peripheral neuromotor system were detected in patients with all forms of the disease; the most characteristic were pronounced electrogenesis disorders in the proximal part of motor nerve axons, particularly in the upper limbs, and of the spinal anterior horn motoneurons at the level of the cervical intumescence.

[Myasthenic myopathy].

We have tested clinical and electrophysiological parameters as well as sera for specific anti-titin-antibodies in 40 myasthenic patients with thymoma, 10 with late-onset and 40 with early-onset without thymoma. We have revealed the prevalence of clinical symptoms: chew and bulbar disturbances, neck and deltoideus muscle weakness in the patients with thymoma and late-onset myasthenia gravis without thymoma. These clinical peculiarities were associated with the absence of changes in duration of minimal motor unit potential after correction for synaptic lesions by proserine injections and increase of titin-antibodies level. The clinical data, along with the results of electrophysiological and immunological studies, suggest a presence of "myasthenic myopathy" in patients with myasthenia, comorbid with thymoma, and patients with late-onset of myasthenia without thymoma.

[Electromyographic evidence in conservative treatment of stress enuresis in women]. / Rezul'taty élektromiograficheskikh issledovanii pri konservativnom lechenii stressovogo nederzhaniia mochi u zhenshchin.

Electromyography (EMG) with needle electrodes of urethral and anal sphincters was performed in 32 patients with stress enuresis (SE). All the patients received conservative treatment as pelvic fundus exercise by Kegel (17 patients), use of vaginal cones (4 patients), ESMP-15-1 device electrostimulation (11 patients). In treatment failure, SE was corrected surgically. The response was assessed 8 weeks after the treatment. Satisfactory results were obtained in 23(72%) women. Reinnervation of urethral sphincter and the anus of different severity was found in 13(41%) and 30(97%) patients, respectively. Denervation in urethral and anal sphincter occurred in 4(13%) and 6(19%) patients, respectively. The comparison of the results of treatment and EMG findings has shown that good results were achieved only in patients with moderate reinnervation of the sphincters. Patients with denervation and/or severe reinnervation of the sphincters did not benefit from the conservative therapy or its result was minimal. It is shown that needle EMG is a reliable method of assessing the condition of urethral and anal sphincters and helps to make timely choice of SE treatment in women.

[Changes in the motor units of the muscles in patients with residual symptoms of poliomyelitis]. / Dinamika izmenenii dvigatel'nykh edinits myshts u bol'nykh s ostatochnymi iavleniiami perenesennogo poliomielita.

Based on an analysis of potentials of motor units (MU) of the skeletal muscles of patients with the postpoliomyelitis syndrome (PPMS), tick-borne encephalitis and spinal amyotrophy, a conclusion is made about the common trend of changes in MU in the given diseases. The degree of changes in MU depends on the grade of physical and trophic load of the preserved nerve elements. As the reserve possibilities of motoneurons are depleted, the process gets aggravated, with the formation of compensatory innervation insufficiency and the rise of muscle atrophy. In patients with PPMS, the decompensation of the pathological process starts, as a rule, at the definite age period and depends on the intensity of the primary defect formation.

[Ultrasonic diagnosis of benign focal lesions of the liver]. / Ul'trazvukovaia diagnostika dobrokachestvennykh ochagovykh porazhenii pecheni.

Proceeding from a study of an ultrasound picture of liver focal changes of benign nature in 60 patients a conclusion was made that nonparasitic cysts could be verified on the basis of a typical ultrasound picture and its stability over time. The presence of daughter cysts and septal membranes was indicative of unilocular hydatid disease. Additional laboratory investigations were necessary for the recognition of alveolar hydatid disease. It was desirable that the diagnosis of liver abscess and hematoma should be confirmed by fine needle spot puncture. By their ultrasound picture benign liver tumors did not differ significantly from malignant ones. To exclude the latter fine needle spot puncture was necessary. Hemangioma should be verified by angiography, the rest of benign tumors--by histology.

[Importance of electromyography in assessing the motor unit function of human skeletal muscles in lesions of the peripheral neuromotor apparatus]. / Znachenie élektromiografii v otsenke sostoianiia dvigatel'nykh edinits skeletnykh myshts cheloveka pri porazheniiakh perifericheskogo neiromotornogo apparata.

Comparison of the parameters of potentials of motor units (PMUs) recorded by a concentric needle electrode and macro-PMUs recorded by a macroelectrode in muscles of 102 patients with various neuromuscular diseases has demonstrated that the results obtained by the given methods of examination provide mutually supportive information about the status of MUs in the patient's muscles, the size of MUs, a possible maximal volume of compensatory innervation and its efficacy.

[Clinico-electrophysiological analysis of mitochondrial myopathy]. / Kliniko-élektrofiziologicheskii analiz mitokhondrial'noi miopatii.

Patients with mitochondrial myopathy have been subjected to clinical, electromyographic, mechanographic, morphological and ultrastructural examination. The main syndromes involving the neuromuscular system in these patients have been considered. The authors draw attention to a generalized character of changes in clinically local lesions. The diagnostic value of electromyographic and morphological examinations has been compared. An analysis of the clinical picture and the results of electromyographic and morphological studies have suggested heterogeneity of the given clinical group of patients.