[Mild and moderate cognitive disorders in elderly].
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Biomedical subjects
Publications and source records attributed to V V Zakharov.
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The paper presents recent clinical data on usage of pronoran, a dopaminergic and noradrenergic medication, in the treatment of mild and moderate cognitive impairment in elderly. Efficacy of pronoran was shown in a number of placebo-controlled as well as open clinical trials including those carried out in Russia. Presented are also the results of the large-scale study PROMETEY which has been performed in Russia in 2004-2005. The study revealed that 70% of elderly neurological patients had cognitive impairment. Pronoran was included in the treatment of cognitive impairment in the frames of this study and showed a marked therapeutic effect in 82% cases.
The mechanism of specific proteolysis of the neuronal protein GAP-43 in axonal terminals has been investigated. In synaptic terminals in vivo and in synaptosomes in vitro GAP-43 is cleaved only at the single peptide bond formed by Ser41; this is within the main effector domain of GAP-43. Proteolysis at this site involves the cysteine calcium-dependent neutral protease calpain. The following experimental evidences support this conclusion: 1) calcium-dependent proteolysis of GAP-43 in synaptosomes is insensitive to selective inhibitor of micro-calpain (PD151746), but it is completely blocked by micro- and m-calpain inhibitor PD150606; 2) GAP-43 proteolysis in the calcium ionophore A23187-treated synaptosomes is activated by millimolar concentration of calcium ions; 3) the pattern of fragmentation of purified GAP-43 by m-calpain (but not by micro-calpain) is identical to that observed in synaptic terminals in vivo. GAP-43 phosphorylated at Ser41 by protein kinase C (PKC) is resistant to the cleavage by calpain. In addition, calmodulin binding to GAP-43 decreases the rate of calpain-mediated GAP-43 proteolysis. Our results indicate that m-calpain-mediated GAP-43 proteolysis regulated by PKC and calmodulin is of physiological relevance, particularly in axonal growth cone guidance. We suggest that the function of the N-terminal fragment of GAP-43 (residues 1-40) formed during cleavage by m-calpain consists in activation of neuronal heterotrimeric GTP-binding protein G(o); this results in growth cone turning in response to repulsive signals.
Neurocognitive functions have been studied in 100 patients with Parkinson's disease (PD). PD was associated with cognitive impairment due to frontal lobes dysfunction, with hippocampus and right hemisphere involvement in advanced stages of the disease. Severity of cognitive impairment increased simultaneously with severity of movement disorder. Patient's age correlated with cognitive abilities. Mild dementia developed in the oldest patients with advanced PD. Besides typical cognitive disturbances, there were more pronounced memory impairment and speech disorders in some patients that might be related to concomitant pathology.
Neurodegenerative diseases accompanied by cognitive impairment (dementia with Levy's bodies--DLB and Alzheimer's disease--AD) and others) are becoming more widespread due to increasing population life expectancy. The paper addresses use of cognitive event-related potential P300 to verbal and nonverbal stimuli with an assessment of interhemispheric asymmetry and topographic distribution of P300 in patients with DLB and AD comparied to age-matched healthy controls. Specific alterations of P300 amplitude and latency suggest a use of cognitive event-related potential P300 in differential diagnosis of DLB and AD.
Frequency of clinical and psychological peculiarities of moderate (mild) cognitive impairment (MCI) in cerebral vascular insufficiency (CVI) was studied in 42 patients, mean age 67.7 +/- 7.7 years. Along with neurological examination, a battery of psychiatric and neuropsychological scales and tests was used. MCI was diagnosed in 28 (66.7%) patients. In 20 patients (47.6%), cognitive hypoactivity was most prominent related to impaired neurodynamics and regulation of voluntary activity which may reflect subcortical and frontal lobes functions. In 8 patients (20.1%), there was a prominent memory impairment characteristic of hippocampus lesion. The authors suggest the presence of concomitant neurodegeneration in patients with amnesic MCI.
Carbon dioxide decomposition in a non-self-sustained discharge was studied by the methods of diode laser spectroscopy and mass-spectrometry. It was shown that the effective control of the mechanism of a plasmachemical reaction is possible by varying the parameter E/N. This allowed us to reduce the energy cost of dissociation CO(2) by more than on an order of magnitude as compared to the dissociation process in a self-sustained glow discharge.
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GAP-43 is a presynaptic protein participating in signal transduction processes in nerve terminals. GAP-43 exists in neurons along with two truncated forms devoid of 4 and 40 N-terminal residues. In this report, we show that these forms of GAP-43 are proteolytic fragments derived from calcium-dependent cleavage of GAP-43 molecule at 5th and 41st residues. GAP-43 site-specific proteolysis in synaptosome and cytosol fractions proved to be dependent on the addition of millimolar amounts of calcium. This fact together with inhibition of GAP-43 proteolysis by calpain inhibitors as well as local composition of the cleavage sites indicates to the participation of calpain in this process. The proteolysis disturbs some properties characteristic for whole GAP-43 molecules, in particular, calmodulin binding and Ser-41 phosphorylation, when the cleavage occurs at 41st residue. Some other GAP-43 properties (G(o) protein activation and membrane attachment) are retained by separate fragments. Therefore, calcium controlled site-specific proteolysis of GAP-43 can be of great physiological significance.
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52 patients with Parkinson's diseases (PD), 11 patients with suspected Alzheimer's disease (AD) and 20 healthy individuals were observed. The age of the examined persons was 55-74 years. Both quantitative evaluation of the neurologic symptoms and estimation of high psychic functions were performed by means of A.R.Luria's method. Memory tests were also used. It was found that PD was practically always accompanied by memory impairments which were out of the normal age limits. The main mechanism of memory impairment in PD without dementia included insufficiency of independent organization of the mnestic activity at the stages of memorizing and reproduction. Besides, a primary disorder was observed in PD with dementia. There were memory impairments in PD with dementia (more crude disturbances of both involuntary memory and processing of information during memorizing) and in AD (disorders of a semantic memory). It was found that disorders of memory trace consolidation were more dependent on the age of PD beginning, whereas insufficiency of the independent organization of the mnestic activity--on its duration. The majority of memory indices correlated in PD with a degree of the disorders of a gait and postural reflexes. It is suggested that memory defects in PD are manifestations of the main pathologic process which had some differences from the other neurogeriatric diseases.
In Donetskiy transplantational centre during the period from 1986 to 1996 yr were conducted 305 operations of the kidney transplantation from the cadaveric and living donor. Kidney transplantation permits to achieve higher level of rehabilitation than while application of hemodialysis and must become the method of choice in treatment of terminal stage of chronic renal insufficiency. Considering large demand for the organs transplantation in Ukraine it is necessary to create an economically substantiated programme "Transplantation of organs".
The experience of 240 renal transplantation operations conduction is summarized. Urinary fistula have occurred in 28 (12%) patients. The causes, clinical signs, methods of diagnosis and principles of treatment of complication are analyzed. The advantages of an active surgical tactics using modern methods, transcutaneous punction pyelo- and nephrostomy under the ultrasound examination guidance, in particular, are substantiated.
The various doses of dopamine efficacy, applied for the inotropic support in 30 donors of kidneys, was investigated, as well as the preparation influence on the renal transplantation function. Inotropic support of donor using dopamine was needed in 21 donors. The occurrence rate of an acute necrosis of tubules have depended upon dopamine doses. Dopamine is the preparation of choice for the intensive therapy conduction and securing of cardiovascular stability of the donors kidneys.
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