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12МЕДИЦИНСКИЕ НАУКИ
Shadlinskaya Ramida Vaqif
Doctor ofphilosophy In Medicine, docent of Dentistry Department Azerbaijan Medical University
Aliyev Ali Nadir
PhD in Biological Sciences, assistant of Biochemistry department Azerbaijan Medical University
Qamidova Qulnara Eldar
Associate researcher of Biochemistry Department Azerbaijan Medical University
THE METABOLIC DISTURBANCE OF IRON AND CALCIUM - CHARACTERISTIC METABOLIC
FACTOR OF THE PATHOGENESIS OF DENTAL AND GENERAL SOMATIC COMORBID PATHOLOGY IN PATIENTS WITH B-THALASSEMIA Major
Summary. The article presents the results of comparison of iron metabolizm, calcium and phosphorus in patients with p - thalassemia. Indirect evidence of hemosiderosis of the parathyroid glands is presented, correlation dependencies of iron accumulation, hypocalcemia and hyperphosphatemia are shown with the activation of cytokines of inflammation - TNFa, Il6, Il10, which increases with the age of the patient. The authors regard the leading accumulation of Il2 as a compensatory reaction of the organism and consider it as a prognostically favorable factor for dental pathology and life of patients with p-thalassemia.
Key words: в - thalassemia, oral disease, iron metabolism, calcium, phosphorus, cytokines of inflammation.
Introduction
P-thalassemia is a hereditary blood disease caused by a genetic defect in the synthesis of the P-chain of hemoglobin. The frequency of its spread among the population in some regions of the world reaches up to 20% or more. In the republics of the South Caucasus and Central Asia, thalassemia affects more than 5% of the population. In Azerbaijan, the prevalence of this gene anomaly is 8%, and in some regions of the republic it reaches 15-20% [1, 2, 11, 17].
Treatment of homozygous patients with p-thalassemia is performed by regular blood transfusions, which quickly leads to overloading of organs and tissues with iron followed by hemosiderosis, which contributes to burdening the general state of the organism. In order to prevent the toxic effects of excess iron, patients are prescribed chelate therapy (desferal), which ensures the binding and excretion of iron from the body [2, 15, 18, 19]
However, it should be noted that the non-specificity of the mineral catharsis effect by chelating compounds leads to excretion of other vital chemical elements from the body of the patients. Thus, the multifac-torial pathogenesis of P-thalassemia and the iatrogenic effects of systematic necessary treatment form polymorbid status in patients, especially including the development of generalized chronic oral inflammatory diseases [7,13,16,22].
Mineral metabolism disorders in thalassemia major are common cause of dental and periodontal complications which require prompt management. In recent years, it has been observed that many authors associate the formation of a mineral imbalance during p-thalas-semia with polyendocrine insufficiency, conditioned by chronic tissue hypoxia under circumstances of hereditary hemoglobinopathy, as well as hemosiderosis of endocrine glands with systematic blood transfusions. [5, 12, 18].
At the same time, it should be noted that until now, when providing dental care to patients with P - thalas-semia, there has been no focus on taking into account
the characteristics of the mineral status of patients, nor scientifically based general, interdisciplinary approaches to dental treatment based on the principles of modern medicine. An important direction in solving this problem is the study of the dynamics of homeo-static changes in the body, associated with regular disturbances in the mineral metabolism in the treatment of patients with p-thalassemia. Correction of these disorders is a subject of the effectiveness of therapeutic and preventive measures of oral diseases. Correction of these disorders is a subject for the effectiveness of therapeutic and preventive measures of oral diseases.
The aim of the work was to determine some metabolic consequences of iron metabolic disorders in p-thalassemic patients with dental and paradontal disease, who receive blood transfusion and chelation therapy.
In this connection, the following tasks were set:
1. To evaluate the parameters of iron metabolism in patients with p-thalassemia in different age groups;
2. Assess the age-related dynamics of calcium metabolism in comparison with the dynamics of changes in iron metabolism;
3. Describe the characteristics of the cytokine blood profile;
4. To study the correlation between the parameters of mineral metabolism and the cytokine status of the organism.
Material and methods. 58 patients with homozygous p-thalassemia were enrolled in the study and divided in 4 main age group: a) in 3 - 5 of ages (7 children) ; in b) in 6 - 12 of ages (23 children) ; c) aged 13 - 17of ages (15 young patients); d) 18- 35 of ages (13 adults). The comparison group was presented by 17 patients with a heterozygous form of p-thalassemia, mean age (14.6 ± 0.3 years). The control group included 16 practically healthy people (mean age 14.1 ± 0.4 years). All patients had different oral and dental disease and get personal dental care and treatment plan. In view of the small difference in laboratory parameters, in the control and comparative groups age categories were not
taken into account. All subjects or their parents/guardians were informed about the study and signed the appropriate consent forms.
In order to identify the concentration level of Il 2, Il 6, Il 10, TNFa the ELISA method with the usage of set of reactive 'Vector BEST' was implemented. The results were taken on StatFax 303+ at a wave length of 450 mm (differential filter 650 mm). Protein content was of blood was identified by the immunoenzymifica-tion analysis. Determination of ferritin was conducted with the help of tools from "Pishtaz Teb diagnostik' (Iran). Whereas hepcidin was determined by the test from "Cloud-Clone Corp" (USA). Enzyme immunoassay methods were also used for determination of oste-ocalcin, osteopontin, calcitonine and parathyroid hormone with the use of commercial tools.
In determination of blood calcium, phosphorus, iron levels and activity of alkaline phosphatase in blood
Parameters of iron metabolism in
serum the photometric methods on biochemical analyzer "STAT FAX 1304 plus" (USA) and commercial tools reactors from "human" (Germany) were used.
Metabolism indicators of iron in blood serum were determined by colorimetric method, with usage of Ni-troPAPS as chromogenic. Determination of ALP activity was conducted by a kinetic method. The obtained digital data were subjected to statistical processing by variational methods (W-Wilkokson, ANOVA), correlation (p-Spearman) and discriminant (Chi-Square) analyzes on the electronic table EXCEL-2010 and SPSS-20.
The results of the study and their discussion.
The results of the conducted studies showed that in patients with p-thalassemia, the expressed body overload with iron, the most significant (p <0,001) with the homozygous form of the disease grows with age (Table 1).
Table 1.
patients in the examined groups
IronMetabolizm Groups N Mean Std. Error 95% ConfidenceInterv alforMean F Sig
Lower Bound Upper Bound
Serum iron ^mol / l control 16 17,8 0,6 16,5 19,1 99,939 ,000
comparison 17 20,6 0,8 18,8 22,4
main 58 38,1 1,0 36,2 40,1
TIBC ^mol / l control 16 61,4 2,6 55,9 66,9 61,317 ,000
comparison 17 51,2 2,5 46,0 56,5
main 58 37,9 0,8 36,2 39,6
LIBC ^mol / l control 16 43,6 2,0 39,4 47,8 202,225 ,000
comparison 17 30,6 1,7 27,0 34,2
main 30 4,7 1,0 2,6 6,8
UIBC % control 16 29,1 0,4 28,3 30,0 258,322 ,000
comparison 17 40,6 0,6 39,4 41,8
main 58 101,9 2,2 97,5 106,3
Ferritin, ng / ml control 16 57,5 4,1 48,7 66,3 190,847 ,000
comparison 17 61,2 4,7 51,2 71,2
main 58 989,3 35,6 918,1 1060,5
Hepsidine, ng / ml control 16 11,8 0,6 10,5 13,2 62,199 ,000
comparison 17 10,4 0,5 9,2 11,5
main 58 30,0 1,3 27,5 32,5
In patients with homozygous ß - thalassemia, attention is drawn to the dynamic decrease in calcium level in the blood parallel to the progressive violation of iron metabolism against a background of significantly high (p <0,001) phosphorus content (Table 2).
The established violation of calcium phosphorus metabolism corresponds to a low level of parathyroid hormone in the blood (p <0.001), which allows to connect the revealed disturbances of mineral metabolism with functional insufficiency of parathyroid glands.
Table 2.
Parameters of calcium-phosphorous metabolism in the examined groups
Calcium-phosphorus metabolism Groups N Mean Std. Error 95% Confidencelntervalf orMean F Sig
LowerB ound UpperB ound
Calcium, mg% control 16 8,42 0,16 8,07 8,76 39,824 ,000
comparison 17 8,51 0,16 8,17 8,86
main 58 7,35 0,07 7,21 7,49
Phosphorus mg% control 16 3,33 0,18 2,95 3,70 44,793 ,000
comparison 17 3,51 0,10 3,29 3,73
main 58 4,64 0,08 4,48 4,79
Osteo-pontin, pg / ml control 16 159,4 7,5 143,4 175,3 108,329 ,000
comparison 17 160,6 7,4 145,0 176,3
main 58 352,5 9,3 333,8 371,2
Osteo-calcine, ng / mg control 16 17,4 0,9 15,4 19,3 92,772 ,000
comparison 17 16,8 0,7 15,2 18,4
main 58 30,1 0,6 28,8 31,4
Calcitonin ng / mg control 16 3,2 0,3 2,5 3,9 44,403 ,000
comparison 17 3,1 0,3 2,4 3,7
main 58 14,6 0,9 12,8 16,4
Parathyroidho rmone pg / ml control 16 39,3 1,4 36,4 42,2 35,052 ,000
comparison 17 40,1 1,8 36,3 44,0
main 58 29,1 0,7 27,7 30,5
ALP, u/L control 16 217,4 8,2 199,8 234,9 95,989 ,000
comparison 17 236,2 11,8 211,2 261,3
main 58 428,9 10,1 408,6 449,1
Our correlation analysis made it possible to establish a high degree of direct dependence of the disorders of iron, calcium and phosphorus metabolism with decreasing paratharmon content in blood, which proves the interrelation of calcium and phosphorus metabolism with hemosiderosis of parathyroid glands. Thus a reverse correlation was found between intact parathyroid hormone (PTH) and Serum iron (r = -0.584), which indicates that the variables PTH and Serum iron are inversely proportional to each other. A special feature was a simultaneous increase in the level of calcitonin in the blood - a functional parathyroid hormone antagonist (Table 2). Osteosclerosis which indicates calcitonin overproduction in combination with osteoporosis is characteristic of bone anomalies in p-thalassemia [14, 21].
The revealed metabolic disturbances developing in patients with homozygous p - thalassemia from an early age are accompanied by a regular wash out of calcium from bone tissue with a high risk of deposition of it in liquid biological medium and in tissue structures. This initiates the pathogenesis of "stone diseases", osteoarthropathies, including temporomandibular joint disorder and is the metabolic basis of the formation and
progression of cranio-dental anomalies typical for p -thalassemia.
The study found that in all patients with p - tha-lassemia major the blood levels of osteopontin and os-teocalcin were 2.2 times higher (p <0.001) than in the control and comparative groups. At the same time, the content of bone proteins in the blood that increases with age evidently has a compensatory character. However, this activation is clearly insufficient to neutralize the developing metabolic disorders, taking into account the crystallopathic nature of the polymorbid incidence of patients with homozygous p-thalassemia.
The increase in the tissue presence of calcium can create an increasing gradient of its concentration, which contributes to the penetration of this element into the cells. Overload of intracellular calcium directly triggers the mechanisms of apoptosis and can activate systemi-cally acting mechanisms of inflammation [3, 4, 6, 8, 9, 10, 20]. Taking into account the above, the obtained data on studying the features of mineral metabolism in patients with p - thalassemia were compared with the results of the study with some parameters of the cyto-kine status (Table 3).
Table 3.
Parameters of pro- and anti-inflammatory cytokines metabolism in the examined groups
N Mean Std. Error 95% ConfidenceIntervalforMean F Sig
LowerBound UpperBound
main - 3-5 7 1,20 0,27 0,54 1,86
main - 6-12 23 1,71 0,17 1,35 2,07
main - 13-17 15 2,28 0,27 1,70 2,86 39,788
main - 17-35 13 2,21 0,25 1,67 2,74
comparison 17 ,38 ,11 ,15 ,60 ,000
Il-2 control 16 ,34 ,08 ,16 ,52
main - 3-5 7 6,76 1,99 1,89 11,62 13 16,7
main - 6-12 23 10,25 0,93 8,32 12,18
main - 13-17 15 9,52 1,17 7,00 12,04
main - 17-35 13 9,09 1,12 6,65 11,53
comparison 17 2,63 ,81 ,90 4,35
control 16 2,29 ,73 ,73 3,86
main - 3-5 7 12,49 4,58 1,28 23,69 1,558
main - 6-12 23 13,44 1,49 10,36 16,53
Il-10 main - 13-17 15 19,56 3,32 12,45 26,67 ,210
main - 17-35 13 14,28 1,82 10,32 18,25
comparison 17 6,02 1,51 2,82 9,22
control 16 6,09 1,46 2,98 9,19
main - 3-5 7 1,44 0,36 0,57 2,31 4,230
main - 6-12 23 1,79 0,15 1,49 2,09
TNFa main - 13-17 15 2,36 0,22 1,88 2,84 ,009
main - 17-35 13 2,49 0,23 2,00 2,99
comparison 17 ,65 ,17 ,30 1,01
control 16 ,59 ,15 ,27 ,92
Studies have also established a marked increase with age with pronounced activation of pro-inflammatory cytokines - TNFa, Il6, Il10 in homozygous patients. Thus, the level of TNFa in the 1st age group is 2.4 times (p <0.05) more than in the control group and 2.2 times higher than in the comparative group (p1 <0.05). In the 3 age group, the TNFa level was 4 times (p <0.001) more than in the control group and 3.3 times (p <0.001) times higher than in the comparative group.
Correlation with increasing iron overload (Table 1), showing a prooxidant effect and directly triggering cascade mechanisms of inflammation, was also confirmed by a high degree of direct dependence of the increasing level of pro-inflammatory cytokines on the dynamics of the increase in hepcidin, the main link between iron metabolism and systemically acting mechanisms of inflammation. For example, il2 positively correlates with hepcidin (p = 0,284; p = 0,031)
Aß
3,0'
1,0-
fir--1-■-1-
3-5 6-12 13-17 18-35
Fig.1. Dynamics of cytokine Л2 v in dependence on age in patients with ß-thalassemia.
Attention was paid to the simultaneous increase with age of the main anti-inflammatory cytokine Il2 (Table 3).
In the youngest age group, the mean Il2 level was 1.20 ± 0.27, which is 3.6 times (p <0.001) higher than in the control group. In the second age group, the mean Il2 score was 1.71 ± 0.17, which is 5.1 times (p <0.001) more than in the control group. In the group of patients aged 13-17 years, the mean Il2 was within the range of 2.28 ± 0.27, which is 6.8 (p <0.001) times higher than in the healthy group. In the group of persons 17 years and above, the average value of Il2 was 2.21 ± 0.25. This is 6.5 times (p <0.001) more than in the control group.
Obviously, the predominance of the anti-inflammatory component in activated cytokine cascades contributes to the demarcation of local inflammatory processes, including in the oral cavity, being the most important factor in the continuation of life in the whole homozygous patients with p-thalassemia under multi-factorial metabolic disorders.
Conclusions:
1. Patients with p-thalassemia suffer from an increased accumulation of glands with age, despite che-lation therapy.
2. The violation of iron metabolism is accompanied by a progressive violation of calcium phosphorus metabolism with a significant (p <0.001) decrease in the level of calcium with a high content of phosphorus in the blood. Considering the reliably low level of parathyroid hormone (p <0.001), the established metabolic disturbances can be associated with parathyroid gland involvement by hemosiderosis.
3. In homozygous patients with p - thalassemia, cytokine imbalance with pronounced activation of pro and anti-inflammatory factors - TNFa, Il6, Il10, and Il2
- increases with age. The predominance of Il2 activity should be considered as a prognostically favorable factor in the development and progress of dental and general pathology.
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Jekaterina Gagarina
Sixth year student Riga Stradins University, Latvia
Ardis Platkajis
Associate Professor Riga Stradins University, Department of Radiology, Latvia
PLAUKSTAS PAMATNES TRAUMATISKO BOJAJUMU MAGNETISKAS REZONANSES UN DATORTOMOGRAFIJAS DIAGNOSTIKAS EFEKTIVITATES SALIDZINAJUMS
WRIST TRAUMATIC DAMAGE - MAGNETIC RESONANCE AND CT SCAN DIAGNOSTICS
EFFICIENCY COMPARISON
Abstract
Introduction: Each year in Latvia the number of patients who have been injured after a sports competition, a direct hits and attacks, or vehicle accidents has been diagnosed with wrist traumas. Early and accurate diagnostics
