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to a lesser extent, increased the degree of destruction in the brain area. The most pronounced morphological and submicroscopic thymus changes occurred in rats with long hypothyroidism. In the majority of cortical slices zone acquires the character of a narrow strip, where portions of closely spaced thymocytes interspersed with light areas that do not contain cells.
The cortical area is often identified large bright pockets containing destructive thymocytes. Hypothyroidism, especially long, accompanied by a significant ultra-structural changes of thymocyte and thymic microenvironment cells. Often identified with signs of thymocytes lysis of the cytoplasm and nucleus pyknosis. Macrophages thymus were characterized by large size, in their cytoplasm often phagocytized thymocytes were found in various stages of destruction.
All this indicated that under the conditions of thyroid hormone deficiency is amplified degree of degradation and death of thymocytes, macrophages are absorbed rapidly. So, conducted studies have shown a direct correlation with postnatal growth of the thymus thyroid condition. We have found that the longer the duration of hypothyroidism, the deeper manifested morphological and morphometric changes in the thymus. Status of the thymus in a violation of thyroid function has been insufficiently studied. In the works of Ukrainian authors demonstrated that the removal of the thyroid gland is accompanied by inhibition of the secretory activity of the thymus in terms of production of thymic hormones. It is known that these hormones are key regulators of the process
of proliferation and differentiation of T lymphocytes and their subpopulations. From our data show that at short hypothyroidism, hypothyroidism and long — lead to a greater extent to decrease the proliferative activity of thymocytes. The degree of degradation is significantly increased in the thymus. This, in turn, contributes to thymic hypoplasia as to reduce its weight and performance of different zones of the thymus lobes. The development of premature thymic involution can be attributed to deficiency of thyroid hormones that have a regulating influence-of the synthesis and secretion of thymic peptides. It is possible that in the pathogenesis of structural and functional disorders of the thymus in a hypothetical-reoza important role played by thyroid and growth hormone anterior pituitary, and thyrotropin-releasing hormone produced by the hypothalamus. From here, it follows that for the natural formation and functioning of the thymus is necessary to have normal levels of thyroid hormones. Prevention of hypothyroidism in childhood and adolescence is one of the important conditions for the normal functioning of the immune system in the adult body.
Conclusions
1. Hypothyroidism develops in the prepubescent period, leading to hypoplastic thymus, the degree of which depends on the duration of the hypothyroid state.
2. Inhibition of activity of the thyroid gland reduces the pro-liferative processes in the thymus and increases the degradation of thymocytes that entails a violation of the processes of T-lymphocy-topoiesis in the body.
References:
1. Akmaev I. G. Modern ideas about the interactions of regulatory systems: the nervous, endocrine and immune//Phys. Fiziol. Sciences. -1996. - Vol. 27, No 1. - P. 3-20.
2. Bolyutskaya L. A., Mars T. P. Clinical and immunological characteristics of patients with immune tireoditom//Immunology. - 2002. -Vol. 23, No 3. - P. 175-177.
3. Mikhailov VA The pathophysiological aspects of hypothyroidism in rats in the experiment/VY. Mikhailenko, V. A. Konplyanko, O. V. Vasilyanskaya, I. G. Postolyuk//Journal of Emergency and Reconstructive meditsiny. - 2012. - T.13 - No 1. - P.86-88.
4. Pods G. Y., Merkulova L. M., Kostrova O. Y., Mikhailov M. N., Moskvichev E. V. Morphological and immune-histochemical examination of the thymus in the normal state and after application polyoxidonium//Bulletin of the University of Chuvashia. - 2012. - No 3. - P. 525-530.
5. Popova N. M. Morphofunctional state of the thyroid gland in the appointment of simvastatin on the background of experimental hypothyroidism/N. M. Popova etc.//Ros. Mediobiol. Herald. Acad. I. P. Pavlova. - 2010. - No 4. - P. 46-51.
6. Pods G.YU., Merkulova L. M., Kostrova O., et al. Morphological and immunohistochemical examination of the thymus in the normal state and after application polyoxidonium//messenger the Chuvash University. - 2012. - No 3. - P. 525-531.
7. Yuldashev M. T. Theoretical and Clinical Medicine Features of formation cytogram thymus at short-term and long-term experimental hypothyroidism caused in prepubertal periode. - 2016 (4) - P. 25-27.
DOI: http://dx.doi.org/10.20534/ESR-16-11.12-112-116
Yusupov Azamat Farkhadovich, JV «SIHAT KO'Z» LLC, Head Doctor E-mail: yafoft@rambler.ru Mukhanov Shavkat Abduvaliyevich, JV "SIHATKO'Z" LLC, Ophthalmologist E-mail: shavkat355@yandex.ru
Ultrasound examination of the carotid arteries in age-related macular degeneration
Abstract: The article is dedicated to the study of frequency of detection and degree of the severity of pathology of carotid arteries in patients with age-related macular degeneration (AMD). 70 patients with different forms of AMD were examined. Among them, there were 30 patients (50 eyes) with early manifestation of AMD; 40 patients with late manifestation: 15 pa-
tients (25 eyes) with atrophic AMD and 25 patients (40 eyes) with different forms of choroidal neovascularization. All patients underwent duplex scanning and color Doppler imaging of brachiocephalic arteries. As result of research, it was revealed that pathological twisting of internal carotid arteries occur in 48% to 64% in patients with AMD, and arterial sclerotic disease of BCA in 65% to 85%. The presented data prove that the change of blood flow in BCA as result of stenosis or pathological twisting is the factor of risk of development of AMD and confirm the important role of hemodynamic factor in the pathogenesis of this disease.
Keywords: age-related macular degeneration, carotid artery, pathological tortuosity, stenosis, duplex scanning, color Dop-pler imaging.
Relevance. Recently, the attention of the ophthalmologists has been drawn by eye diseases determined by chronic ischemia and hypoxia of the organ ofvision, which are related to stenotic disease or pathological twisting of brachiocephalic arteries (BCA). Most authors refer age-related macular degeneration (AMD) along with other eye diseases to the manifestations of chronic eye ischemia [3, 121-125; 6, 110-131].
Currently, four fundamental theories ofAMD pathogenesis are considered: primary aging of retinal pigment epithelium and Bruch's membrane, damages by the products of lipid peroxidation, primary genetic defects and pathological changes of blood flow of the eye ball [2, 106-109; 9, 413-424; 10, 430-433; 11, 473-482].
In 1937, F. H. Verhoeff and H. P. Grossman presented the information about the role of system and local vascular factors in the AMD pathogenesis for the first time. Later, the interest to this problem increased and the vascular theory took the leading place in the explanation of reasons ofAMD appearance [2, 106-109; 13, 3771-3777].
Most publications are dedicated to the study of the role of atherosclerotic disease of carotid arteries and system arterial pressure in the development and progression of the AMD symptoms. Currently, it's been established that people with atherosclerosis of carotid arteries have higher risk ofAMD development than in the general population; herewith, it is established that atherosclerotic disease of the arteries of other basins does not play any role in the progression of the given pathology [2, 106-109; 8, 4624-4631]. Moreover, the increased arterial pressure is not a factor of risk of AMD development, but the frequency of cases of disease increases if it is associated with stenotic diseases of carotid arteries [2, 106-109; 12, 4722-4727]. The significant role in the development of AMD is given to cardiovascular diseases. E. F. Cherney (2001) notes that in atherosclerosis, the risk of the disease of macular area increases by 3 times, and by 7 time in the presence of hypertonic disease. Atherosclerosis plaques of the common carotid increase the risk of AMD development by 2,5 times; plaques in the area of bifurcation of carotid arteries — by 4,7 times [4, 42-45; 6, 110-131]. E. S. Abdulaeva (2002), Yu. M. Lagutina (2006) registered the changes of blood flow in the system of internal carotid artery (ICA) at non-exudative forms of AMD [5, 3-22].
Thus, presented literature data indicates that the change of blood flow in the carotid arteries as result of occlusions, stenosis or pathological twisting leads to the disorder of local eye blood flow and is a factor of risk for the development of vascular pathology of the eye and AMD symptoms. However, the questions about the frequency of occurrence of BCA disorders and their peculiarities — character and degree of expressiveness ofpathologies depending on the clinical form of AMD, remain open.
Aim. To study the condition of blood flow and evaluate the degree of expressiveness, frequency of detection of pathological changes of brachiocephalic arteries in patients with different clinical forms of age-related macular degeneration.
Materials and methods. 70 patients with different forms of AMD aged from 50 to 85 (65,5±5,8 years old) were examined.
Among them, there were 30 patients (50 eyes) with early manifestation of AMD (hard and soft drusen, defect and migration of pigment epithelium of retina); 40 patients with late manifestation: 15 patients (25 eyes) with atrophic AMD and 25 patients (40 eyes) with different forms of choroidal neovascularization (CNV).
The criteria of exclusion of patients from the study included:
1) any form of glaucoma;
2) impossibility of ophthalmoscopy (cicatricle opacity of cornea, cataract, consequences of uveitis);
3) presence of detached retina;
4) presence of thrombosis of the central vein or obstruction of the central artery of retina;
5) presence of diabetic retinopathy of any stage;
6) presence of myopia of high degree with long anterior-posterior axis of the eye ball over 26 mm;
7) presence of intra-cranial damage of optic tract and disease of optic nerve;
8) presence of diabetes in the stage of decompensation;
9) presence of oncological diseases;
10) presence ofpsychical diseases, including alcoholism.
It should be noted that in the work, every examined eye was accepted as a separate clinical case of disease and, in further presented material, we factually considered not as much the number of patients as the number of eyes affected with ADM and BCA from same-name side.
The control group included 15 volunteers comparable in age and sex without the signs ofAMD.
All groups were statistically homogenous and comparable according to the presence, severity and character of co-existing details. Among general diseases, the examined patients were most often diagnosed with arterial hypertension, hypertonic disease, ischemic heart disease, type I and II diabetes, chronic disorders of cerebral circulation, circulatory encephalopathy. The diagnosis and treatment of common diseases were established by the specialists: therapist, cardiologist, endocrinologist and neurologist.
Apart from the standard common ophthalmological examination, all patients underwent duplex scanning and color Doppler imaging (CDI) with the use of multi-functional ultrasound diagnostics device SonoAce R7 (SAMSUNG MEDISON CO., LTD., Republic of Korea) with the use of linear detector with frequency 7 MHz to evaluate the condition of the blood flow in BCA. The specter of the Doppler shift of frequencies was registered and main quantitative and qualitative parameters ofblood flow were defined. The detector was placed over the jugular notch in parallel to the internal edge of sternocleidomastoid muscle. Changing the inclination of the detector to the surface of the neck, clear visualization of the mouth of the common carotid artery (CCA) was received. The sinus of CCA and its bifurcation were located behind the corner of the lower jaw; during the examination of ICA, the detector was turned in the lateral direction. During the visual evaluation of the vascular bed, the vascular permeability (permeable, obstructed), flow direction (presence of deformations — bends, twists, loop formations), di-
ameter of the vessel (normal, reduced, increased), movability of the vascular wall (rigidity, hyper pulsation), condition of perivascular tissues (density, presence of various pathological formations) were taken into account. The luminal occlusion of uniform diameter is lower than echogenicity of the surrounding tissues; the internal surface of the intima. The thickness of the complex intima-media is not more than 1 mm in normal state.
The degree of the expressiveness of stenosis of carotid arteries was established according to the classification of the European association of carotid surgery (1991): 1) small stenosis — 0-29%; 2) moderate stenosis — 30-49%; 3) expressed stenosis — 50-69%; 4) critical stenosis — 70-99%; 5) occlusion — 100% [7, 1478-1480].
The pathological twisting of ICA was assessed according to the form of elongation: C and S-shaped twisting, bends at sharp points (kinking), loop and spiral shaped twisting (coiling), double bends and combined twisting.
According to the hemodynamic characteristics of blood flow in ICA, hemodynamically significant and hemodynamically insignificant violations were distinguished. According to the generally accepted classification of stenosis of carotid arteries, the degree of stenosis over 60% was considered hemodynamically significant [1, 25-54]. The criteria of hemodynamic significance of pathological twisting of ICA were:
1) gradient of peak systolic velocity of blood flow between proximal and distal sites of the vessel relative to the place of twisting with the reduction ofvelocity in distal direction by 20% and more;
2) growth of peak velocity in the place of angulation compared with the proximal site of BCA by 30% and more;
3) disorganization of blood flow in the zone of twisting manifested in the increase of spectral expansion and disruption of color pattern of blood flow in CDI regime.
The obtained data was subjected to statistical processing with the help of the program Statistica 6,0. The quantitative indicators were processed by the methods of descriptive statistics and presented in the form of the arithmetical mean and its standard
error (M±m). Absolute number and relative value in percentage (%) were indicated for the indicators characterized by qualitative signs. The criterion of Kolmogorov-Smirnov was used to check the hypothesis of normality of distribution of quantitative indicators. In the vent of deviation from normal distribution, Mann-Whitney U-test was used to compare data. Student t-criterion was used in the event of correspondence of data to the normal distribution. Achieved level of significance (p) was calculated in all procedures of statistical analysis, herewith, the critical level of significance in this study was equal 0,05. Relative risk of effect was evaluated according to odd ratio (OR). To check statistical hypotheses about differences of absolute and relative frequencies, shares and relations in two independent selections, x2 criterion was used with the Yate's correction with regard to continuity. Confidence intervals (CI) presented in the work were built for confidence probability p=95%.
Results and discussion. As result of ultrasound examination of ICA in patients with initial manifestation of AMD, 48% of cases showed different forms of deformations of vessels without signs of hemodynamically significant acceleration of blood flow (Table 1). Out of which, C-shaped pathological twisting of artery was noted in 22% of cases and S-shaped pathological twisting — in 18% of cases. Moreover, the kinking twisting was revealed in 6% of cases and coiling twisting — in 2%. In the group of patients with geographical atrophy of pigment epithelium of retina (PER), pathological twisting of ICA was observed in 64% of patients. Among them, 28% had C-shaped twisting, 20% — S-shaped twisting, 8% — kinking and 4% — coiling, and 4% had double bends. In the group with neo-vascular AMD, pathological twisting of ICA was diagnosed in 60% of cases. Among them, 25% of cases had C-shaped twisting of the vessel, 20% — S-shaped twisting, 10% — kinking and 5% — coiling. The correlation of chances of occurrence of pathological twisting of ICA in patients with AMD was established most in the group with geographic atrophy PER — by 3,1 times compared with the control group; in the group with neo-vascular AMD, this indicator was 2,86 and in the group with early manifestations of AMD — 1,6.
Table 1. - Frequency of occurrence of pathological twisting of ICA in patients with different clinical forms of AMD
Form of PT Early manifestation of AMD (n=50) Geographic atrophy PER (n=25) Neo-vascular AMD (n=40) Control group (n=30)
Number of cases % Number of cases % Number of cases % Number of cases %
C-shaped 11 22,0 7 28,0 10 25,0 5 16,7
S-shaped 9 18,0 5 20,0 8 20,0 3 10,0
Kinking 3 6,0 2 8,0 4 10,0 2 6,7
Coiling 1 2,0 1 4,0 2 5,0 1 3,3
Double bedns - 0,0 1 4,0 - 0,0 - 0,0
Total 24 48,0 16 64,0 24 60,0 11 36,7
x2; p* 0,57; 0,45 3,06; 0,08 2,86; 0,09 -
OR** (95% CI) 1,6 (0,63-4,03) 3,1 (1,02-9,26) 2,6 (0,98-6,87) -
Remark: * - level of significance of differences compared with the data of control group ** - correlation of chances to the data of control group
Table 2. - Frequency and degree of stenosis of CCA in patients with different clinical forms of AD
Degree of stenosis Early manifestation of AMD (n=50) Geographic atrophy PER (n=25) Neo-vascular AMD (n=40) Control group (n=30)
Number of cases % Number of cases % Number of cases % Number of cases %
1 2 3 4 5 6 7 8 9
No stenosis 12 24,0 3 12,0 6 15,0 11 36,7
Small stenosis 21 42,0 5 20,0 9 22,5 9 30,0
1 2 3 4 5 6 7 8 9
Moderate stenosis 17 34,0 17 68,0 25 62,5 10 33,3
Total with stenosis 38 76,0 22 88,0 34 85,0 19 63,3
x2; p* 0,91; 0,34 3,17; 0,07 3,28; 0,07 -
OR** (95% CI) 1,8 (0,68-4,91) 4,2 (1,03-17,5) 3,3 (1,05-10,3) -
Remark: * - level of significance of differences compared with the data of control group ** - correlation of chances to the data of control group
Table 3. - Frequency and degree of stenosis of ICA in patients with different clinical forms of AMD
Degree of stenosis Early manifestation of AMD (n=50) Geographic atrophy PER (n=25) Neo-vascular AMD (n=40) Control group (n=30)
Number % Number % Number % Number %
of cases of cases of cases of cases
No stenosis 24 48,0 8 32,0 14 35,0 18 60,0
Small stenosis 12 24,0 7 28,0 10 25,0 5 16,7
Moderate stenosis 14 28,0 10 40,0 16 40,0 7 23,3
Total with stenosis 26 52,0 17 68,0 26 65,0 12 40,0
x2; p* 0,65; 0,42 3,24; 0,07 3,37; 0,07 -
OR** (95% CI) 1,6 (0,65-4,07) 3,2 (1,05-9,70) 2,8 (1,05-7,40) -
Remark: * - level of significance of differences compared with the data of control group ** - correlation of chances to the data of control group
Thus, the results of examination of ICA in patients with different clinical forms of AMD showed that from 48% to 64% of cases had pathological twisting of this or that form. It should be noted that with the severity of the course of dystrophy of macular zone, the growth of frequency of detection of pathological twisting of ICA is noted.
According to the data of ultrasound studies of BCA in patients with early manifestations ofAMD, stenosis of CCA was diagnosed in 76%, out of which, 42% — small stenosis and 34% — moderate stenosis (Table 2). More significant differences compared with the control group were revealed in patients with late manifestations of AMD: in the group with geographic atrophy PER — 88% (20%
small and 68% moderate stenosis), in the group with neo-vascular AMD — 85% (22,5% small and 62,5% moderate stenosis).
The stenosis of BCA was detected in small degree compared with the stenosis of CCA (Table 3). Thus, in the group with early manifestations of AMD, 52% of patients are observed, and in the group with geographic atrophy PER — 68%; in the group of patients with neo-vascular AMD — 65%. It should be noted that more than half of cases had moderate stenosis.
Thus, the results of ultrasound study of the condition of ICA showed that with the progression of dystrophic process, from initial manifestations to atrophy PER. There is a tendency towards the increase of frequency of detection and degree of stenosis.
Table 4. - Indicators of the ultrasound study of CCA and ICA in patients with different clinical forms of AMD; (M±m)
Parameters Early manifestation of AMD (n=50) Geographic atrophy PER (n=25) Neo-vascular AMD (n=40) Control group (n=30)
CCA
Vs (cm/s) 60,2±3,4 45,8±3,4* 52,8±3,8 58,5±4,2
Vd (cm/s) 17,9±1,8 15,6±1,5 16,5±1,4 20,4±1,9
RI 0,69±0,06 0,79±0,06 0,77±0,03 0,62±0,06
Degree of stenosis (%) 27,8±2,1 32,1±1,7** 31,5±1,8* 25,5±1,7
CIM (mm) 1,28±0,04 1,39±0,05* 1,36±0,05* 1,21±0,05
ICA
Vs (cm/s) 59,1±2,3 49,8±3,5* 51,6±3,7 61,2±4,1
Vd (cm/s) 24,6±1,7 21,6±1,4 22,3±1,3 25,1±1,6
RI 0,72±0,07 0,78±0,05 0,76±0,04 0,69±0,05
Degree of stenosis (%) 25,8±1,8 29,4±1,6** 28,5±1,9* 22,5±1,8
CIM (mm) 1,25±0,06 1,37±0,06* 1,34±0,05* 1,18±0,06
Remark: * - level of significance compared with the data of control group (p<0,0S) ** - level of significance of differences compared with the data of control group (p<0,0l)
Duplex examination of the condition of blood flow in ICA in patients with AMD showed the decrease of velocity parameters of blood flow in different degree and increase of the complex of intima-media (CIM) compared with age-related norm (Table 4). Compared with age-related norm, significant reduction of velocity of blood flow and increase of the complex of intima-media (p<0,05 or p<0,01) was noted in patients with late manifestation
of AMD, which certified about atherosclerotic changes of vascular wall. In the group with early manifestations of AMD, the reduction of hemodynamic indicators of blood flow of ICA compared to the norm was present in all cases; herewith, we didn't detect statistically significant changes.
Thus, most examined patients had pathological twisting of ICA and atherosclerotic damage of BCA. Possibly, this leads to the disor-
der of blood circulation in eye vessels due to the reduction of elasticity of vascular wall determined by age-related changes as well as because ofhemodynamic load at the increase of arterial pressure and combination of age-related changes in arteries with changes of the condition of blood flow. The high percentage of cases (48-64%) of pathological twisting of ICA and (52-85%) atherosclerotic damage of BCA in examined patients indicates the significance of this factor in the pathogenesis of AMD.
Conclusions
1. The presented data prove that the change of blood flow in BCA as result of stenosis or pathological twisting is the factor of risk of development of AMD and confirm the important role of hemo-dynamic factor in the pathogenesis of this disease.
2. The frequencies of occurrence of pathological twisting of ICA in patients with different forms ofAMD were revealed: with early manifestations of the disease — in 48% of cases, in patients
with geographic atrophy PER — in 64% of cases, in patients with neo-vascular AMD — 60%.
3. Peculiarities ofpathological twisting of ICA in AMD was revealed: C-shaped twisting occurs in 25% of cases; S-shaped twisting — in 19% of cases; kinking — in 19%, coiling — in 3,5% and double bends in 1,5% of patients.
4. Atherosclerotic disease f CCA and ICA in patients with AMD occurs in 85% and 65% respectively; herewith, there is a tendency towards the increase of the frequency of occurrence of damage and degree of stenosis with the progress of dystrophic process.
5. Moderate stenosis of CCA and ICA occurs in 34% and 28% of cases, in early manifestations ofAMD, in 62,5% and 40% in neo-vascular, 68% and 40% in geographic atrophy PER.
6. The degree of stenosis of BCA in geographic atrophy PER and neo-vascular AMD reaches significant level compared with the group of control and early manifestations of AMD.
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