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Neuron-specific protein S100B as a diagnostic marker Parkinson's disease
Matmurodov Rustambek Jumanazarovich, Khalimova Khanifa Mukhsinovna, Rashidova Nilufar Safaevna, Tashkent Medical Academy E-mail: [email protected]
Neuron-specific protein S100B as a diagnostic marker Parkinson's disease
Abstract: The paper presents the results list immunoassay neuroglia protein S100B in patients with Parkinson's disease, compared with a control group of patients without symptoms of Parkinsonism. The study involved 22 patients with PD, aged from 34 to 63 years. The highest activity of the protein S100B is set at akinetic-rigid form, and in the early stages of the disease than later. S100B maximum activity was observed at the opening of the disease up to 49 years and 6 months to 1 year duration. Neuron-specific protein S100B levels in the serum can be a diagnostic marker for Parkinson's disease.
Keywords: Parkinson's disease, diagnostics, protein S100B.
Parkinson's disease (PD) is one of the most urgent problems of modern clinical neurology, due to its high prevalence in older age groups, and a clear trend to a "rejuvenation" of the disease in recent years [2; 5]. It is estimated that approximately 60% -80% of cases of Parkinson's disease occur in PD. BP frequency among the neurodegenerative diseases is second only to Alzheimer's disease (V. L. Gol-ubev et al., 2005, N. N. Yahno et al., 2006, J. C. Morris, 2006).
It is known that the basis of steadily progressive neurodegenerative disease is Parkinson what lies constant neuronal death. It is noted output neuron-specific enzymes and their proteins of damaged brain cells into the extracellular medium, which allows them to increase the depth and intensity to find structural and functional disorders of biological membranes in the central nervous system
[1; 3].
Especially in recent years, there has been increased interest in the clinical use of brain markers such as S100B proteins. For the diagnosis and prognosis ofvarious diseases is of great importance in the determination of S100B protein serum [2]. Neuroglia protein S100B is a specific protein of astrocytes glial cells capable of binding calcium. The name protein was due to the property to remain in solution in a saturated solution of ammonium sulfate [8]. Astroglial cells — this is the most numerous cells in the brain tissue. They form three-dimensional network, which is a reference frame for neurons [6; 7].
There is growing evidence that S100B acts as a cytokine or damage associated molecular protein are formed not only inflammatory, but also in neurodegenerative diseases. PD is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons and glial cells may be involved in the pathophysiology of this disease. According to the authors of S100B has potential value as a marker of the severity of the disease [4].
Objective: to study the activity of the protein S100B in the blood serum ofpatients with Parkinson's disease, depending on the age of patients, duration, clinical form and stage of disease.
Material and methods: The material of this study was 31 patients receiving inpatient and outpatient treatment in the 1-Re-publican Clinical Hospital Ministry of Health of the Republic of Uzbekistan. The study group included 22 patients with PD, including 13 (59.1%) males and 9 (40.9%) women. Patients ranged in age from 34 to 63 years (mean age 50.4±6.6 years). Duration of the disease — is 0.5 to 8 years. The diagnosis of PD was set based on the criteria of the bank brain disease, Parkinson Society of Great Britain (Hughes A. J. et all, 1992). Evaluation stage of
the disease was performed using scale- Hoehn and Yahr [Hoehn M., Yahr V. D., 1967]. The severity of PD was determined Using standardized rating scale assessment manifestations PD (Unified Parkinson's Disease Rating Scale- UPDRS), the initiate movement disorders. The control group consisted of 9 patients without symptoms of Parkinson's disease; all patients underwent the necessary clinical and diagnostic testing, including specification of anamnestic data, the study of neurological status, CT or MRI (magnetic resonance imaging) of the brain.
Determines the content of S100B in the blood serum by enzyme immunoassay performed with specific test systems developed on the basis of appropriate monoclonal antibodies on the analyzer Hospitex Diagnostics, Italy according to the instructions supplied with the kit. Subsequently conducted a comparative evaluation of the results of analyzes of S100B in patients for age, duration of clinical form and stage of disease. Statistical analysis was performed using the parametric Student t-test. To determine the significance of differences in qualitative traits used analysis of contingency tables.
Results and discussion: In the studied group of patients with PD enrolled in the study, it was found a slight predominance of males (59.1%). Among all patients were recorded significantly more mixed forms of PD and stage II disease. It was observed the largest number of individuals of40-49 years of age groups. Age debut BP varied between 34 to 63 years, averaging 50.4±6.6 years. The mean duration of PD was 4.25±2.8 years. The debut of the disease more common in the age is 40-49 years (40.9%). Thus for akinetic-rigid forms of the PD was characterized by an earlier onset of the disease (49 years).
The study on the content of S100B serum of patients with PD level was increased, while in the basic group was 132.5±6.5 ng/l and the control group, 72.6 ± 2,6 ng/l (p<0, 05). An analysis of S100B levels in the examined patients with PD revealed that contain protein studied varied depending on the age of patients. Comparing the activity of serum S100B in individuals of both groups according to age, it was found that among the patients in the control group there were no statistically significant differences. While the activity index S100B in PD patients had statistically significant differences depending on age. It was found that in patients less than 60-69 years average S100B 164.3±2,3ng/l, when the level of 50-59 S100B 121.7±3,5 ng/l, and aged 49 years 97.1±5.9 ng/l (p<0.05). Patients in the control group there were no significant differences in the age ofthe patient, whereas 71.8±10,8 -70,8±8,5-75,2±9,4 ng/l, respectively. (Fig.1.)
Section 6. Medical science
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GO-G9 years 50-59 years 49 years Figure 1. S100B protein levels in serum according to age of patients (ng/l)
We conditionally allocated patients into 3 groups depending on the duration of the disease: one group of patients, the duration ranged from 6 months to 1 year, 2 patients from group 1 to 3 years and 3-band more than 3 years. These results show that the level S100V
serum depends on the duration of the disease, whereas the duration of more than 3, the level of the protein was observed at a higher level than the duration of 6 months to 1 year, 102,4±4,6 ng/l — 143,7±5.2 ng/l — 168.7±4,5 ng/l, respectively. (Figure 2).
IS100B t
Figure 2. S100B protein level in the serum, depending on the duration of PD. (ng/l)
In the next phase of the study, we studied S100B levels in the serum of patients with PD, depending on the form of the disease. The results show that the level of protein in the serum of pa-
tients with joint was 166.1±2,5 ng/l, whereas the shape of tremor 121.8±3,5 ng/l and akinetic-rigid form 104.7±9,1 ng/l. (Figure 3).
Control Akinetic-rig id Tremor Mixed
Figure.3. Active S100B in the blood serum of patients with PD depending on the clinical form At the same time, the activity of serum S100B PD patients had (Figure 4). The flow through the stages PD depends on the clinical
statistically significant differences from the stage of the disease. So patients stage III PD have higher rates than the stage I and II, 166,6±3,5 ng/l — 129,7±5,1 ng/l — 100,8±4,9 ng/l, respectively.
manifestations, 3-stage of the disease is more severe clinical manifestations, while the serum levels of S100B patients may occur at a high level.
Figure 4. The level of the activity of S100B in the blood Conclusion: The research activity of S100B in the blood serum of patients with PD revealed that this figure varied depending on age, duration, clinical form and stage of disease. The highest activity of the neuron-specific protein S100B is installed in mixed form, and in the later stages of the disease when compared with the initial. S100B maximum activity was observed at the opening of the disease up to 49 years, and the minimum — in 60-69 years. And as the level of activity of S100B
serum of patients with PD, depending of the stage serum it depends on the duration of the disease. The activity of S100B serum of patients with PD indicating the severity of a neurodegenerative process they are already in the early stages, compared with a control group of patients. Thus, it was found that the evaluation of clinical status BS necessary to carry out enzyme immunoassay for the determination of S100B levels and this could be used as one of the other methods for early diagnosis and prognosis of brain neurodestructive processes.
Study of gene — candidate marker's levels in patients with non-burdened and burdened familial history of NFPA...
References:
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5. Yahno N. N., Nodel M. R. Modern principles of treatment of Parkinson's disease. Eng. honey. Zhurnal.-2000.-№ 8.-page. 418-426.
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Kholova Dilorom Sharifovna, Khalimova Zamira Yusufovna, The Republican Specialized Scientific-Practical Medical Center of Endocrinology of the Republic of Uzbekistan, Tashkent.
E-mail: [email protected]
Study of gene — candidate marker's levels in patients with non-burdened and burdened familial history of NFPA (non-functioning pituitary adenomas)
Abstract: Early diagnostics of NFPA relates to difficult questions of modern neuroendocrinology that even high-informative computer tomographs (CT) and magnetic resonance imaging (MRI), and also clinical-laboratory, immunofermental — hormonal researches do not provide the right answer in 30-55% of cases, and at microadenomas (the tumor sizes is up to 10 mm) in 90 100% of cases. At a stage of microadenoma NFPA s are seldom diagnosed and often accidentally discovering during diagnostic. The diagnosis is defined, as a rule, when adenoma has already reach a considerable size, causing occur sight violations, headache and other neurologic symptoms connected with an invasion of tumor in the cavity of skull and structure of the basis of skull. As references showed NFPA is met in 25-43% of pituitary adenomas and up to 10% of all intra cranial tumors. Due to the progress of medical genetics, molecular biology there was a possibility to expand the pathogenesis representation of NFPA. Molecular and genetic researches showed that up to 5% of NFPA cases refer to genetically predisposed people. At the same time in literature there is practically no comparative data on clinical course and disease diagnostics in populations between sporadic and family NFPA disease. Researches implemented in this direction will allow improving preclinical diagnostics, to differentially approach to tactics of treatment of NFPA patients.
Keywords: non-functioning pituitary adenomas, the family anamnesis, molecular and genetic researches, early diagnostics.
In recent years, the efforts of researchers about study of the etiopathogenesis of NFPA directed to find out the molecular and genetic factors. Introduction of modern achievements of genetics and molecular biology in all basic and clinical medicine areas has significantly changed our understanding of the etiopathogenesis and, consequently, the ability to diagnose, treatment and prevention of many diseases. In endocrine system, genes have a relation to the realization ofvarious functions, encoding protein hormones, receptors, enzymes, steroid biosynthesis, intracellular signaling molecules, transport proteins, ion channels, transcription factors and other molecules. In present it is known that many endocrine diseases have a hereditary nature, as NFPA [9], associating with a defect of a particular gene or being characterized polygenic mode of inheritance [5; 6]. At the same time in the development of NFPA
there are not data about inheritance causes at the level of groups of genes derived from the structure and the biological function of the encoded protein molecules [3; 6].
On the strength of experience of the world genetics it can be confirmed that the majority of NFPA are genetically determined, although the disease in close relatives is not always possible to identify [1,2,4]. Identified familial history of NFPA in our study consisted of 25 cases, including panmixia — 11 and inbreeding — 14 patients.
Based on the above, the purpose of our study was to determine the level of gene markers — candidates in patients with non-burdened and burdened familial history of NFPA.
Materials and methods. We carried out the study to identify in 20 patients with non-burdened familial history (1 group) and in 25 patients with burdened familial history of NFPA (2 group)
