=Paper=
{{Paper
|id=Vol-2753/paper35
|storemode=property
|title=Applying of Information Technologies for Study of the Thyroid Gland Follicular Thyrocytes’ Synthetic Activity
|pdfUrl=https://ceur-ws.org/Vol-2753/paper23.pdf
|volume=Vol-2753
|authors=Olha Ryabukha,Ivanna Dronyuk
|dblpUrl=https://dblp.org/rec/conf/iddm/RyabukhaD20
}}
==Applying of Information Technologies for Study of the Thyroid Gland Follicular Thyrocytes’ Synthetic Activity==
https://ceur-ws.org/Vol-2753/paper23.pdf
Applying of Information Technologies for Study of the Thyroid
Gland Follicular Thyrocytes’ Synthetic Activity
Olha Ryabukhaa and Ivanna Dronyukb
a
Lviv Medical Institute, Polishchuk str. 76, Lviv, 79018, Ukraine
b
Lviv Polytechnic National University, S. Bandera str. 12, Lviv, 79013, Ukraine
Abstract
Mathematical methods, which are traditionally used in biomedical diagnostics, operate on
quantitative data, which makes it impossible to use them in the study and interpretation of
qualitative cytophysiological data. Descriptive (linguistic) approaches that use the principles
of fuzzy logic are becoming more and more widespread in the study of qualitative biomedical
information. The combination of modern information technology and cytophysiological
concepts permits a holistic cybernetic understanding of cell activity as a supersystem with
complex links between its subsystems. In the presented work, the complex use in the thyroid
follicular thyrocytes study of such mathematical approaches as correlation analysis, the
principle of phase interval, mathematical statistics, quantitative analysis of electron
microscopy images and the method of determining profiles of hormone-producing cells’
special capabilities, which permits to transform qualitative (linguistic) characteristics of
thyroid gland thyrocytes’ organelles into quantitative parameters with their further
transformation and the obtained results objectification by means of correlation portraits. The
data obtained in this way were used to analyze the dependences of some constituent elements
of the cell (cell organelles) on other ones in studying the influence of the same factor on the
peculiarities of cell activity changes in different experimental conditions.
Keywords 1
mathematical methods in cytology, biomedical research, thyroid gland, iodine deficiency,
inorganic iodine, thyrocyte, synthesis of thyroid hormones
1. Introduction
Holistic view of the cell as a supersystem with complex relationships between its components
should be formed using mathematical methods, which can be used to determine the main features of
its functioning. Today, advances in information theory and cybernetics permit to apply mathematical
technologies in almost all spheres of life: data obtained through mathematical analysis can be used to
formulate hypotheses about the dependence of some phenomena on others [1,2]. They can be
especially important in the study of normal cell activity and pathology [3]. At the same time,
physiological and pathological processes have a number of interrelated features of qualitative and
quantitative nature, which ultimately are the most appropriate in terms of its structure and appropriate
for realization of potential opportunities. The main features of the cell as a biological system are: a
certain property of its constituent elements, their manifestations intensity, the type of connections
between the elements, the density of connections between the components of the system. Each
element of such a system can be in different states - normal vital activity, excitation, functional stress,
emergency regulation, functional or organic changes, according to which their characteristic
IDDM’2020: 3rd International Conference on Informatics & Data-Driven Medicine, November 19–21, 2020, Växjö, Sweden
EMAIL: oriabuha@ukr.net (Olha Ryabukha); ivanna.m.droniuk@lpnu.ua (Ivanna Dronyuk)
ORCID: 0000-0001-6220-4381 (Olha Ryabukha); 0000-0003-1667-2584 (Ivanna Dronyuk)
©️ 2020 Copyright for this paper by its authors.
Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).
CEUR Workshop Proceedings (CEUR-WS.org)
morphofunctional features are formed. If the properties of each element in the system are described
using certain parameters and variables, their transformations can be displayed in the form of
functional dependencies [4].
An original approach to the involvement of mathematical technologies in the process of studying
the activity of hormone-producing cells was first published [5] and proposed as a method of studying
changes in their functional activity under the influence of various factors [6]. This permits using
mathematical technologies to reveal the patterns of physiological and pathological processes, to
clarify their patterns and to predict the consequences of various processes.
Modern biomedical diagnostics as a fundamental element of medical science is increasingly using
the possibilities of mathematical analysis. Any task of biomedical diagnostics can be considered as
search for data display:
X * ( x1* , x2* ,xn* ) d j D (d1 , d 2 ,d m ), (1)
where X* is the set of parameters of a particular patient’s condition/organ/cell/organelle and D is the
set of diagnoses.
To solve the problems of biomedical diagnostics, the most widespread are mathematical methods,
such as Bayesian analysis [7], regression analysis [8], the logical programming [9]. Summarizing the
possibilities of their use, it should be noted that they are poorly adapted to work with quality (non-
numerical) databases [10]. However, in biomedical practice, the analysis of qualitative information,
which is given in linguistic form and is mostly heuristic, is very important for correct diagnosis.
To solve various biomedical problems that require mathematical processing of non-numerical
(linguistic) information, fuzzy set theory is increasingly used [11]. For the successful implementation
of biomedical diagnostics using fuzzy logic it is necessary to adhere to the principle of linguistic
diagnosis, parameters of the patient's condition and the principle of linguistic diagnostic data [12].
Unlike traditional models, which are built on the principles of quantitative mathematics, the adequacy
of fuzzy logical statements does not change with slight fluctuations in the experimental conditions. At
the same time, practical application of fuzzy set theory for the study of biological objects or diagnosis
is quite cumbersome, and a clear gradation of the biological system’s states is not always possible. An
important reason is the lack of a sufficient number of specially trained experts.
The use of electron microscopy permits to study in detail the basic level of the living matter’s
hierarchical organization - cellular organelles in the norm and in the restructuring of their
substructural components in the conditions of impaired functional balance and pathology. The study
of cell ultraarchitectonics is carried out in several ways. The most commonly used is descriptive
method, which involves the use of words in the language used. The linguistic approach to the analysis
of the electron microscopic picture of the studied tissue has undeniable advantages. They include a
detailed status quo statement, reflection of the studied ultrastructures state nuances, the capability to
draw conclusions about the system’s functional state. At the same time, this approach is purely
empirical and has significant shortcomings, such as subjectivity in description, the need for highly
qualified specialists to carry out studies, the inability to use the results for further mathematical
transformations in the need to analyze the process course or to predict its consequences. The use of
computer software, which can be used to determine the area or percentage of certain structural
components in the cell cytoplasm, enriches the research potential in the study of ultrathin cell
structure.
However, display of the cell state by means of unrelated numbers does not solve the problem of a
comprehensive study of its activity, as it does not always permit to correctly determine the degree of
structural changes, their direction and functional significance. Given the shortcomings of the
descriptive (linguistic) approach to the study of electron microscopy images and determination of the
percentage of individual organelles in the cell, it seems possible to apply the principle of fuzzy logic.
An example of using this approach to the study of the thyroid gland’s follicular thyrocytes can be a
description of their morphofunctional state with reduced functional activity:
“If the shape of the cell is prismatic; electron density of cytoplasm - insignificant; electron density
of colloid - is insignificant; apical microvilli - very thick, very thin, long; the number of apical
microvilli - is significant; mitochondria in small quantities; the value of the rough endoplasmic
reticulum elements - is significant; the magnitude of the Golgi apparatus elements - is significant; the
number of free ribosomes and polysomes - is insignificant; the number of lysosomes - is insignificant;
the number of apical secretory granules - is insignificant, then the functional activity of the thyrocyte
is reduced (pathological).”
A significant advantage of this approach to the study of electron microscopy images is the
capability of mathematical transformations with subsequent conclusions and generalizations. At the
same time, it is not adapted to determine all the nuances of the morphofunctional state, in which the
cell is.
Thus, medical diagnostics is a decision-making process in a cybernetic system with n input
parameters (cause/signs of the condition) and a single output parameter, which is the consequence/
conclusion/diagnosis. Although the need to develop modern diagnostic decision-making systems in
various fields of medicine is extremely urgent, the tools for creating such systems for cytology need
significant improvement. This is primarily due to the insufficient efficiency of those mathematical
methods that are traditionally used to model the relationships between condition parameters and
diagnosis. In addition, they are not adapted to study the functional activity of the cell, which
significantly limits the development of scientific knowledge in the field of cytology.
2. Purpose of the study
Based on the analytical generalization of scientific literature, to determine the capability of using
common mathematical methods for studying the ultrathin structure of hormone-producing cells and,
based on the results of our own observations, to choose the most informative method to determine the
characteristics of changes in hormonal cells ultrastructures under the effect of medicinal products, that
permits to make substantiated conclusions both on the reliability of cytophysiological study and the
efficacy of the applied means for correcting endocrine disorders.
3. Materials and methods of the study
The main research methods were:
Analytical review, synthesis and generalization of data obtained from scientific literature
sources on the research topic.
Mathematical statistics [13]. Numerical data for assessing the number and condition of
cellular ultrastructures are used to determine x - the arithmetic mean and m - the standard deviation
of the arithmetic mean, which is calculated by commonly used formulas.
The principle of phase interval [14,15]. The condition or number of studied cellular
ultrastructures is compared to two diametrically opposed controls - the norm and the studied untreated
pathology.
Elements of correlation analysis [16]. The cell is considered to be a complex negentropic
system, the subsystem of which is a certain studied field of its activity. To establish the relationships
between its constituent elements and to study their strength and direction, the pairwise correlation
coefficients are determined, which are calculated according to Pearson's formula (2):
i n
(2)
( x x)( y y)
i i
rxy i 1
,
i n i n
( x x) ( y y )
i 1
i
2
i 1
i
2
where rxy - coefficient of pair correlation between the indices х and у; xi - the х index value in і -
observation; yi - the у index value in і-observation; n - number of observations, x - mean value of
the х index for n observations performed; y - mean value of the у index for n observations performed
[4].
A positive value of the pairwise correlation coefficient rxy indicates the same direction of the
studied index’es changes, negative value means that with the increase in one of the indices another
index associated with it decreases; the rxy value = 1.0 indicates the existence of a direct proportionality
between the indics x and y, rxy = –1.0 mean inverse proportionality. In the structural organization of
relationships between the indices, the most significant are considered to be very strong and strong
correlations, which on the Chaddock scale of linear correlation [17] are within the range of 1.0 ≥ r xy ≥
0.91 and 0.9 ≥ rxy ≥ 0.71, respectively; in the absence of such correlations, significant correlations
0.7≥ rxy ≥ 0.51 are taken into consideration.
Fundamental principles of fuzzy set theory are: the principle of linguistic diagnosis and the
patient's condition parameters, and the principle of linguistic diagnostic data [18].
Semi-quantitative analysis of electron microscope images [6]. The analysis of electron
microscope images of follicular thyrocytes’ ultrastructures is performed according to a certain
algorithm. Numerical assessment of the symptoms manifestation degree of ultrastructural elements is
carried out using graphic symbols or a point/percentage scale. Absence of a sign is assessed as 0
points, insignificant manifestations - 1 point, moderate manifestations - 2 points, significant
manifestations - 3 points, the maximum manifestations of a sign - 4 points. The increase in the
number of ribosomes is proposed to be assessed in proportion to the degree of its severity within the
range from 4 to 8 points. The scale for assessing the signs manifestations in the semi-quantitative
analysis of electron microscope images is given in Tab. 1.
Table 1
Scale for assessing the symptoms manifestations
Symptom manifestation Graphic Numerical assessment
degree symbol (points) (percentage)
feature absent - 0 0
weak + 1 25
moderate ++ 2 50
significant +++ 3 75
maximal ++++ 4 100
Note. 0 points - state of unattended pathology under study ("disease"); 4 points - state of the
studied pathology complete absence ("health")
Method for determining the profiles of hormone-producing cells’ special capabilities [6]. If
any field of a hormone-producing cells’s activity is qualified as "opportunity" and cellular
ultrastructures which implement it are defined, the consequence of such quantification will be creation
of narrow specialized clusters - profiles of the respective opportunities. For the mathematical analysis
of the obtained data, each quality of each ultrastructural element is attributed the appropriate symbol
with the subsequent digital assessment of the signs’ manifestations degree. In our work, we present
the ultrastructural components to the profile of the thyroid gland follicular thyrocytes’ synthetic
capability (Tab. 2).
Table 2
Ultrastructural components to the profile of the thyroid gland follicular thyrocytes’ synthetic activity
Ultrastructural Studied feature of the Status of the studied Symbol legend of the
element ultrastructural element ultrastructural element studied ultrastructural
feature element feature
Cytoplasm electron insignificant В1
density
moderate B2
significant B3
Rough endoplasmic structure constricted J1
reticulum
(rough ER) normal J2
increased J3
number of membrane reduced J4
bound ribosomes
moderate J5
increased J6
Free ribosomes number reduced K1
(in cytoplasm)
and polysomes moderate K2
increased K3
Golgi apparatus structure constricted L1
normal L2
expanded L3
The study was carried out on 20 white nonlinear male rats with the initial body weight of 140–
160 g, which under standard vivarium conditions consumed an isocaloric semi-synthetic starch-casein
iodine deficient diet. Group 1 rats were kept under the conditions of unpotentiated alimentary iodine
deficiency; in rats of group 2 alimentary iodine deficiency was potentiated by administering the
thyrostatic drug mercazolyl (Mercazolyl-Health, RF) at the dose of 3 mg/kg body weight. Correction
of iodine deficiency in animals of both groups was carried out with inorganic iodine at the dose of
100 μg/kg body weight. The duration of the experiment was 30 days; during observation and
euthanasia, the principles of bioethics were observed in compliance with the European Convention for
the Protection of Vertebrate Animals Used in Experiments (Strasbourg, 1986) and Council of Europe
Directive 2018/63/ CV.
The subject to study were electron microscope images of ultrathin (4–6 μm) thyroid glands
sections in rats of both groups made according to generally accepted methods. Processing of the
obtained results was performed by the scale for assessment of thyrocyte ultrastructural elements’
manifestations using the semi-quantitative analysis of electron microscope images (Tab. 1) by means
of software: for digital data - StatSoft Statistica v6.0 package, for correlation tables and portraits -
Microsoft Office 2010 package - electronic MS Excel spreadsheet and MS Word graphic editor
(Microsoft Graph), respectively.
4. Results and discussion
In order to avoid the shortcomings inherent in the considered methods of cell research, we
proposed a method of constructing correlation portraits in different fields of hormone-producing cells‘
activity [6]. Interpretation of the obtained data is carried out from the standpoint of cytophysiology,
taking into account the functional significance and role of each cellular ultrastructure [19,20].
As an example of our method’s informativeness in the study of functionally related conditions, we
present correlation portraits with their description and cytophysiological interpretation of the
interdependencies established between cellular organelles that synthesize hormones in follicular
thyrocytes of the thyroid glands. In the given case, the synthesis is carried out under the conditions of
varying severity hypothyroidism:
1. caused by alimentary deficiency of iodine (less severe).
2. caused by alimentary iodine deficiency, potentiated by consuming the thyrostatic drug
mercazolyl (more severe).
4.1. Database of significant data for constructing correlation portraits
The presence of correlation connections between ultrastructural elements of the synthetic activity
of the thyroid glands follicular thyrocytes in rats, their strength and direction are presented in Тab. 3,
and Tab. 4.
Table 3
Сorrelations between the constituent elements of the synthetic direction portrait of thyroid glands
follicular thyrocytes’ activity in white male rats who were corrected alimentary iodine deficiency
with a large dose (100 μg) of inorganic iodine
Interdependent ultrastructural elements of the portrait Correla-
Ultrastructu- tion,
Characteristics of the studied ultrastructural elements ral elements (r)
features
legends
moderate number of bound ribosomes - moderate number of free J5 – К2 1.000
ribosomes
normal structure of rough ER - moderate number of bound ribosomes J2 – J5 0.612
normal structure of rough ER - moderate number of free ribosomes J2 – К2 0.612
increased structure of rough ER - expanded structure of Goldgi J3 – L3 0.612
apparatus
increased structure of rough ER - normal structure of Goldgi apparatus J3 – L2 0.612
moderate number of bound ribosomes - normal structure of Goldgi J5 – L2 0.667
apparatus
moderate electron density of cytoplasm - increased structure of rough B2 – J3 –0.612
ER
moderate number of free ribosomes - normal structure of Goldgi К2 – L2 –0.667
apparatus
expanded structure of Goldgi apparatus - normal structure of rough ER L3 – J2 –0.612
Table 4
Сorrelations between the constituent elements of the synthetic direction portrait of thyroid glands
follicular thyrocytes’ activity in white male rats who were corrected mercazolyl-potentiated
alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
Interdependent ultrastructural elements of the portrait Correla-
Ultrastructu- tion,
Characteristics of the studied ultrastructural elements ral elements (r)
features
legends
reduced number of free ribosomes - normal structure of Goldgi К1 - L2 1.000
apparatus
normal structure of rough ER - moderate number of bound J2 - J5 0.764
ribosomes
reduced number of bound ribosomes - moderate number of free J4 - K2 0.873
ribosomes
moderate number of free ribosomes - expanded structure of Goldgi K2 - L3 0.764
apparatus
insignificant electron density of cytoplasm - moderate number of free B1 - K2 –0.801
ribosomes
moderate electron density of cytoplasm - increased structure of B2 - J3 –0.764
rough ER
increased structure of rough ER - reduced number of free ribosomes J3 - К1 –0.873
increased structure of rough ER - normal structure of Goldgi J3 - L2 –0.873
apparatus
moderate number of bound ribosomes - moderate number of free J5 - K2 –0.764
ribosomes
insignificant electron density of cytoplasm - moderate number of B1 - J5 0.612
bound ribosomes
moderate electron density of cytoplasm - moderate number of bound B2 - J5 0.667
ribosomes
moderate electron density of cytoplasm - reduced number of free B2 - К1 0.667
ribosomes
reduced number of bound ribosomes - expanded structure of Goldgi J4 - L3 0.667
apparatus
reduced number of free ribosomes - expanded structure of Goldgi К1 - L3 0.667
apparatus
normal structure of Goldgi apparatus - expanded structure of Goldgi L2 - L3 0.667
apparatus
expanded structure of Goldgi apparatus - insignificant electron L3 - B1 –0.667
density of cytoplasm
moderate number of bound ribosomes - increased number of bound J5 - J6 –0.667
ribosomes
4.2. Correlation portraits of follicular thyrocytes’ synthetic capability,
description and interpretation of traced correlations
When consuming 100 μg of inorganic iodine under the conditions of alimentary hypothyroidism
due to iodine deficiency, we established only 1 very strong correlation (1.0 ≥ | r | ≥ 0.91) and did not
trace strong (0.9 ≥ | r | ≥ 0.71) correlations, therefore the study was carried out using significant (0.7 ≥
| r | ≥ 0.51) correlations, which there were 8; 5 of them being indirect (Fig. 1).
Figure 1: Ranking by the number and strength of significant correlations traced between protein-
synthesizing ultrastructures of thyroid follicular thyrocytes in male white rats who were corrected
alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
The actual signs of the synthetic capability profile’s correlation portrait when consuming 100 μg of
inorganic iodine under the conditions of alimentary hypothyroidism due to iodine deficiency were B2,
J2, J3, J5, K2, L2, L3 (Fig. 2). The focal points of the portrait were J2, J3, J5, K2, L2, which formed
3 relationships, and L3 (2 relationships). The structure of the portrait was unstable: due to the
predominance of indirect correlations (5 out of 9 significant ones in total), it had a great tendency to
change.
Figure 2: Graphic representation of the correlation portrait profile structure of the thyroid glands
follicular thyrocytes’ synthetic activity of white male rats who were corrected alimentary iodine
deficiency with a large dose (100 μg) of inorganic iodine
It was found that under the studied conditions the Goldgi apparatus was of paramount importance
for thyroid hormonal poetics. Thus, the synthesis of hormones occurred by the coordinated interaction
of Goldgi apparatus and rough ER ultrastructures, which were in the same functional state: the
expanded elements of Goldgi apparatus (L3) interacted (r = 0.612) with the expanded ultrastructures
of rough ER (J3). Indirectly, this is confirmed by indirect correlations of the same force (r = –0.612)
traced between the extended elements of the Goldgi apparatus (L3) and moderately expressed (normal
structure) elements of rough ER (J2) and between Goldgi apparatus substructures of moderate
(normal) size (L2) and extended elements of rough ER (J3).
A very strong relationship between moderate amounts of ribosomes on rough ER membranes (J5 -
bound ribosomes) and in the cytoplasm of thyrocytes (K2- free ribosomes) indicates the correlation
between ribosomes of different localization and may indicate the prerequisites for the normal course
of the synthetic process in the cell. At the same time, the synthetic activity of thyrocytes occurred
against the background of a certain functional stress. This is evidenced by the indirect correlations of
the Goldgi apparatus elements, which were moderate in size (L2) with a moderate number of
ribosomes on rough ER membranes (J5) and a moderate number of ribosomes in the cytoplasm (K2).
Thus, in the conditions of alimentary hypothyroidism caused by iodine deficiency, consuming a
large (100 μg) dose of inorganic iodine has a moderately beneficial effect on the interaction between
the organelles that implement the synthesis of the hormonal product. In particular, the increasing role
of the Goldgi apparatus, in which the maturation of hormone molecules takes place, has been
established, which can be logically interpreted as a sign of the hormonopoiesis completion. However,
the presence of certain dissociations between the morphofunctional states of protein-synthesizing
organelles indicates the preservation of functional stress due to iodine deficiency, which does not
decrease when consuming 100 μg of inorganic iodine.
The actual signs of the ultrastructural elements state in the correlation portrait of the thyrocytes
synthetic capability profile when consuming 100 μg of inorganic iodine under mercazolyl-potentiated
alimentary hypothyroidism due to iodine deficiency were B1, B2, J2, J5, K4, L2, L3, between which
the following correlations are traced: very strong (1,0 ≥ | r | ≥ 0,91) - 1, strong (0,9 ≥ | r | ≥ 0,71) - 8
(from them 5 being indirect). For the objective characterization of the portrait, noticeable (0.7 ≥ | r | ≥
0.51) correlations were studied, of which 8 were established - 2 of them being indirect (Fig. 3).
Figure 3: Ranking by the number and strength of significant correlations traced between protein-
synthesizing ultrastructures of thyroid follicular thyrocytes in male white rats who were corrected
mercazolyl-potentiated alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
The main focal points of the portrait were J5, L3 (5 corelations in total) and B2, K2, L2 (which
had 4 significant correlations); focal points J3 and B1 formed 3 significant correlations. The
architectonics of the portrait was characterized by symmetry, its structure – by stability and low
ability to change (Fig. 4).
Figure 4: Graphic representation of the correlation portrait profile’s structure of the thyroid glands
follicular thyrocytes’ synthetic activity in white male rats who were corrected mercazolyl-
potentiated alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
The strong relationship between moderate (normal structure) rough ER substructures (J2) and
moderate number of ribosomes on its membranes (J5) indicates sufficient synthetic thyrocyte activity.
Indirectly, this is confirmed by indirect correlations of the same strength which rough ER with
extended substructures (J3) formed with moderately pronounced (normal structure) elements of the
Goldgi apparatus (L2), reduced number of free ribosomes and polysomes (K1) and moderate electron
density of cytoplasm (B2).
Consuming a large dose (100 μg) of inorganic iodine caused a functional stress of the thyrocyte, as
evidenced by the involvement of a significant number of ultrastructures in the synthetic process. In
particular, we observed four complexes of correlations with different composition and strength: a very
strong correlation of the Goldgi apparatus with moderately expressed (normal) substructures (L2) and
a small number of (free) ribosomes in the cytoplasm (K1); strong correlation of a small number of
bound ribosomes (J4) and a sufficient (normal) number of free ribosomes (K2); a direct strong
correlation of a sufficient number of free ribosomes (K2) and a Goldgi apparatus with extended
elements (L3) and an indirect correlation of a sufficient number of free ribosomes (K2) and a small
electron density of the cytoplasm (B1); a noticeable correlation between the Goldgi apparatus with
extended elements (L3) and a small number of free ribosomes (K1). In addition, the strong correlation
of a sufficient number of free ribosomes (K2) with the extended elements of the Goldgi apparatus
(L3) and the strong indirect correlation of K2 with a low electron density of the cytoplasm (B1) may
indicate that the number of free ribosomes is not is crucial for the protein-synthesizing function of the
Goldgi apparatus.
Therefore the large number of dissociations between morphofunctional states of such important for
synthetic thyrocyte activity ultrastructures as Goldgi apparatus and (free) cytoplasmic and (bound)
membrane-fixed rough ER ribosomes, indicates that when potentiating alimentary hypothyroidism
with mercazolyl in the conditions of iodine deficiency consuming a large dose (100 µg) of iodine not
only leads to significant functional stress of the thyrocyte, but can also significantly impede the
thyroid hormones synthesis.
Thus, the practical application of our method has shown its great informative value in
cytomorphological studies. With its help it is established that in the conditions of impaired functional
balance caused by both alimentary deficiency of iodine, and the combined influence of alimentary
iodine deficiency and the thyrostatic drug mercazolyl, preconditions for realization of the thyrocyte’s
synthetic activity remain. At the same time, correction of iodine deficiency by administering a large
dose (100 µg) of inorganic iodine excessively activates its activity, which increases functional stress,
and potentiation of alimentary iodine deficiency with mercazolyl may lead to impaired thyrocyte
adaptation to these adverse factors.
We also found the features of ribosomes participation in the synthesis of thyroid hormones in
different functional states of the thyroid gland. The correlations established between ribosomes and
other protein-synthesizing organelles permitted to determine the peculiarities of the synthetic process
in terms of unpotentiated and potentiated iodine deficiency (Tab. 5). In the presented Fig. 5, and
Fig. 6, the differences in the correlations of ribosomes with other protein-synthesizing ultrastructures
under the studied conditions are well observed. For better perception of information, the organelles
that are the closest to the norm in their characteristics are marked with green color. Organelles that are
far from the norm in opposite directions are marked: when the characteristics decrease - violet-
colored, when they increase - marked with orange.
Under the conditions of consuming a large dose (100 μg) of inorganic iodine in unpotentiated
alimentary iodine deficiency (Fig. 5) the correlation between sufficient numbers of ribosomes fixed
on the rough ER (J5 - bound ribosomes ) membranes, and ribosomes located in the thyrocyte
cytoplasm (K2 - free ribosomes) indicate the equal value of both free and fixed ribosomes for the
hormonal synthesis processes.
Figure 5: Scheme of significant direct correlations traced between ribosomes and other profile
components of the thyroid follicular thyrocytes’ synthetic activity in white male rats who were
corrected alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
Instead, in the conditions of mercazolyl-potentiated alimentary iodine deficiency, consuming a
large dose (100 μg) of inorganic iodine leads to impaired hormonopoiesis. This is evidenced by the
numerous correlations of reduced (K1) or moderate (K2) number of free ribosomes with other
ultrastructures, which functional states are not adequate for the number of ribosomes (Fig. 6). Strong
correlations of free ribosomes moderate number (K2) with reduced number of bound ribosomes J4
(r = 0.873) and moderate number of bound ribosomes J5 (r = –0.764) indicate differences in the
functional purpose of ribosomes with different intrathyrocyte localization. This promotes a more
detailed study of ribosomes involvement in the synthesis of thyroid hormones: the number, location
and correlations of ribosomes with other protein-synthesizing ultrastructures are determined by the
functional status of the thyrocyte and change accordingly. In this case, a detailed description of the
thyrocyte ribosomes’ status can serve as a marker of the appropriate morphofunctional changes.
Figure 6: Scheme of significant direct correlations traced between ribosomes and other components
of the synthetic activity profile of white male rats’ thyroid follicular thyrocytes who were corrected
mercazolyl-potentiated alimentary iodine deficiency with a large dose (100 μg) of inorganic iodine
Table 5
Changes in thyroid follicular thyrocytes’ protein-synthesizing activity according to the results of
ribosomes interrelations analysis with different localization among themselves and with other
protein-synthesizing substructures
Experimen- Type and number Protein-synthe- Significant correla- Importance of
tal condi- of ribosomes sizing cellular tions between ribo- established
tions substructures somes and protein- correlations
synthesizing cellu- for synthetic
lar substructures activity
Iodine bound moderate normal structure 0.612 ↑
deficiency of rough ER (moderate
in the diet increase)
moderate moderate number 1.0 ↑↑↑
of free ribosomes (intense
increase)
moderate normal structure –0.667 ↘
of Golgi (moderate
apparatus impairment
with functional
stress)
free moderate normal structure 0.612 ↑
of rough ER (moderate
increase)
moderate normal structure –0.667 ↘
of Golgi apparatus (moderate
impairment
with functional
stress)
Potentiated bound reduced moderate number 0.873 ↑↑
iodine of free ribosomes (significant
deficiency Increase)
in the diet reduced extended structure 0.667 ↑
of Golgi apparatus (moderate
increase)
moderate normal structure 0.764 ↑↑
of rough ER (significant
increase)
moderate insignificant 0.612 ↑
electron density (moderate
of cytoplasm increase)
moderate moderate 0.667 ↑
electron density (moderate
of cytoplasm increase)
increased moderate –0.667 ↘
number of bound (moderate
ribosomes impairment
with functional
stress)
free reduced extended structure –0.873 ↘↘
of rough ER (significant
impairment
with functional
stress)
reduced moderate 0.667 ↓
electron density (moderate
of cytoplasm impairment)
reduced normal structure 1.0 ↘↘↘
of Golgi apparatus (intense
impairment
with functional
disorder)
reduced extended structure 0.667 ↘
of Golgi apparatus (moderate
impairment
with functional
stress)
moderate reduced number of 0.873 ↑↑
free ribosomes (significant
increase)
moderate extended structure 0.764 ↗↗
of Golgi apparatus (significant
increase with
functional
stress)
moderate insignificant –0.801 ↘↘
electron density (significant
of cytoplasm impairment
with functional
stress)
moderate moderate –0.764 ↘↘
number (significant
of bound impairment
ribosomes with functional
stress)
Note. The number and direction of the "arrow" symbol indicates ranking of the intensity and
direction of changes in the protein-synthesizing activity of follicular thyrocytes
5. Conclusions
1. Mathematical methods, traditionally used in medicine, operate mainly with quantitative data,
and the method of fuzzy logic, which uses qualitative information, does not permit to take into
account all the nuances of cellular ultrastructures’ condition and requires a rather strict determinism,
which is not always possible to achieve in cell studies. This actually makes it impossible to use these
methods for the needs of cytophysiological studies.
2. The combination of mathematical and morphological methods proposed for studying the activity
of hormone-producing cells can be attached to modern biomedical information technologies, as it is
an independent research method, by which the features of cell morphophysiology are studied from the
standpoint of its priority self-regulation. This permits to analyze the relationships between cellular
ultrastructures (their presence, direction, strength) and deepens the understanding of cell function in
different states and conditions, which greatly expands the possibilities of cytophysiology as a science.
3. The use of a package of such interrelated mathematical and morphological methods as
fundamental elements of correlation analysis, the principle of phase interval and mathematical
statistics, semi-quantitative analysis of electron microscope images and determination of profiles for
special capabilities of hormone-producing cells permits to transform qualitative characteristics of cell
organelles into quantitative parameters with the capability of further objectifying the results obtained.
An important feature of the proposed research method is the lack of strict determinism, which is not
inherent in biological objects.
4. The use of ideas about the cell as a complex self-regulatory system, in which the point of
application of different factors having the same direction of influence are different organelles with the
similar functional specialization, permits to identify and analyze the existing differences in cell
activity according to their manifestations and force.
5. Construction of correlation portraits in certain fields of cell activity, their further analysis and
generalization permit to study the relationships and interdependencies between ultrastructures in
different functional states of the cell and contribute to the detailed characterization of ultrastructural
changes influenced by different factors in different living conditions. In this case, the correlation
portrait becomes a multi-component multivariate expert system.
6. The represented method of studying the hormone-producing cells by constructing correlation
portraits of certain fields of its activity permits to characterize the nuances of its condition and to
establish the functioning features not only at the time of study, but also permitting to study changes in
intimate mechanisms of hormonopoiesis and to determine reserve and potential capabilities.
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