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Some Aspects Of The Pathogenesis And
Diagnosis Of Teething In Newborns
Khabiba Kamalbekovna Isakhojaeva
1
, Shakhnoza Badriddinovna Daminova
2
, Abdugafur
Akhatovich Khajimetov
3
1
Senior Lecturer, Department of Biochemistry, Tashkent State Dental Institute, Tashkent,
Uzbekistan
2
Head of the Department of Biochemistry, Tashkent State Dental Institute, Tashkent,
Uzbekistan
3
Professor, Department of Biochemistry, Tashkent State Dental Institute, Tashkent,
Uzbekistan
I.
INTRODUCTION
Teething is its axial movement from a non-functional position in the jaw bone to a functional
occlusion. The dynamics of this process depends on the degree of formation of the root,
periodontium and is closely related to the development and growth of the craniofacial
complex. Teething is one of the links in a complex chain of processes of the physiological
development of the child, which begins in the prenatal period and lasts for several years.
Teething is characterized by quantitative and qualitative indicators (1-13). Teething is an
important factor in assessing the development and formation of the baby’s dentition. Various
factors influence teething. A number of researchers believe that the genotype of a person, his
constitution, is of primary importance in the process of teething, although the role of various
ABSTRACT
The aim of this study was to evaluate some aspects of the pathogenesis and diagnosis of
teething in newborns based on the study of the dynamics of estrone in breast milk and the
saliva of a newborn. 78 practically healthy lactating women with obesity-38 and 30 who
were not obese were examined, as well as their newborns. Object of study, saliva and
blood plasma. It was revealed that the hormonal profile of a newborn in saliva with a
change in metabolism in lactating women can undergo certain changes. As lactation
develops in women with excess div weight, hormone estrone undergo intensive
elimination from milk, which leads to a decrease in its content in breast milk, which can
affect metabolic processes in the newborn's dentofacial system.
KEY WORDS:
obesity, newborns, breast milk, estrone, teething
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external environmental factors cannot be ruled out (17-26) By the time of teething, the
portion of the bone covering the tooth crown is resorbed. The same processes are noted in the
gum. During the growth of the tooth root, there is also a bone remodeling and a gradual
deepening of the dental alveoli. At the same time, morphological changes in the tissues
surrounding the tooth occur: increased blood flow, changes in vascular permeability,
increased production of the main substance of the pulp and periodontium (14-45). Since
teeth, like bone, are highly mineralized tissues, the development of teeth and the surrounding
bone tissue occurs in a constant relationship. The movement of the tooth to the alveolar edge,
overcoming the barriers of bone tissue and mucous membrane and its appearance in the oral
cavity is considered to be an inexplicable process. Therefore, such theories of teething as
root, alveolar, pulpar, bone tissue remodeling were created and until recently remained in the
educational literature [8, 32, 43, 45, 46].
T.E. Zueva [2003] believes that the influence of the nervous and endocrine systems,
metabolism and alveolar bone in the embryo, malnutrition, heredity, and geographical
conditions play an important role in dentition. Recognizing the regulatory role of the nervous
and endocrine systems in teething, I.V. Gayvaronsky (2003) notes that “differentiation of
tooth tissues, accompanied by an increase in volume and the creation of a certain pressure
(strain) inside the germ, is important. The restructuring of the bone tissue in front and behind
the embryo is of great importance, determines its movement.”
The effect of hormones on the growth and development of the human div is of great interest
not only to pediatricians, hygienists, endocrinologists, but also to dentists. In the hormonal
growth system, L. Wilkins calls growth hormones, the thyroid gland, as the main hormones
that control growth and development. sex hormones present in the div in a strictly defined
ratio for each stage of development (39). It is widely believed that the main stimulator of
histogenesis of cartilage, bone and dental tissues is the pituitary somatotropic hormone, and
the thyroid hormone controls tissue differentiation (22,38,39). It has become known that
growth hormone cannot manifest its growth action without thyroxine, insulin,
glucocorticoids, sex hormones (38).
In the process of growth, sex hormones are actively involved, which are in a certain
relationship with the activity of the central and peripheral endocrine glands. After birth and in
early childhood, the amount of sex hormones is small, but with age it increases [7, 9-11, 30].
Due to the anabolic effect, sex hormones affect the structure of the basic substance of the
bone, accelerate the growth and differentiation of the skeleton, and also have a significant
effect on the mineralization of calcified tissues. The influence of female and male sex
hormones in their biological orientation on the creative processes in bone tissue is somewhat
different. The final sizes of growth and various growth rates of boys and girls are considered
as manifestations of dimorphism, which is determined by the influence of sex hormones
(5,15,17). The most active was synestrol tooth growth under its influence increased by 22-
41% compared with indicators in intact animals and by 11-29% in castrated animals.
Testosterone increased tooth growth by 10-23 and 1-13%. Differences in the biological
effects of female and male sex hormones were also expressed in the fact that the greatest
increase in teeth (by 29-41%) caused synestrol when a small dose (300 μg) was administered,
and testosterone (by 13-23%) when a high dose of the drug (1000 μg) (19,21,24). By exerting
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a pronounced anabolic effect and contributing to the calcification of highly mineralized
tissues, synesterol and testosterone accelerated tooth growth and bone formation.
Progesterone led to a greater increase in teeth (by 22.7%).
Thus, it is established that the developing tissues of the tooth are sensitive to hormonal
changes, and the degree of change depends on the dose and type of hormone. Acceleration
and deceleration of the growth and development of teeth under the influence of hormonal
changes (castration, the introduction of sex hormones) should be interpreted as a hormone-
dependent process.
Taking into account the foregoing, it can be assumed that teething delay (ZPZ) is a hormone-
dependent process and can affect the formation of the jaws and facial part of the skull. Often,
ZPZ is the primary, and sometimes a single manifestation of a local or systemic pathology.
Such features of growth and development may be the motive for a thorough history and an
additional examination of the patient. ZPZ, being a reflection of regional and systemic
deviations from the norm, requires close attention from specialists in collecting anamnesis
and assessing the clinical situation, making a diagnosis, choosing treatment methods and
predicting treatment results (7.8). The information presented to a certain extent will facilitate
the construction of a "diagnostic tree" when working with ZPZ.
A study conducted by numerous researchers indicates that the critical time for growth and
teething is from 8 pm to 1 hour after midnight. In the morning and during the day of growth,
almost no growth is observed, which indicates the circadian rhythm of growth rhythms
associated with hormonal peaks during the day. The literature contains information on the
content of hormones in female milk, as well as hormonal relationships between mother and
child during the lactation period. The foregoing was the prerequisite for an in-depth and
comprehensive study of the hormonal composition of human milk in the dynamics of
lactation.
Obesity is one of the most common chronic diseases in the world. According to modern data,
every fourth inhabitant of our planet suffers from some degree of obesity or is overweight (9).
According to 2014 WHO, more than 1.9 billion adults over 18 years of age are overweight
(10). Of this number, over 600 million people are obese. Fat cells secrete a number of
hormones, cytokines, which provoke the development of inflammatory diseases that have
common pathophysiological bases with obesity. Numerous studies have traced the
relationship between the pathology of endocrine organs and tooth growth. Growth retardation
and delayed teething are described after removal of the pituitary gland (21,22,40), with
cerebrohypophysial
dwarfism
and
hypogenitalism,
congenital
atyroidism
and
hypothyroidism, adipozogenital dystrophy (22).
Based on the foregoing, the purpose of this study was to evaluate some aspects of the
pathogenesis and diagnosis of teething in newborns.
II.
MATERIALS AND METHODS
The object of the study was 78 practically healthy lactating women aged 20-27 years living in
the city of Tashkent. In accordance with the objectives of the study, patients were divided
into 2 groups: group 1, patients with obesity-38 and group 2 of patients without obesity -30
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puerperas. The main group of studies consisted of patients with criteria suitable for the
diagnosis of obesity. The diagnosis was made using the data of anthropometric studies of
patients, determination of div mass index (BMI)> 30.0 (kg / m2) and overweight (> 25.0 kg
/ m2.).
Exclusion criteria from the study: chronic renal failure, type 1 diabetes mellitus, severe
anemia, pregnancy and lactation, cancer, respiratory failure, medications that affect bone
level, resorption and gingival hypertrophy.
A copy of the data from the history of childbirth showed that pregnancy and childbirth in all
examined women were characterized by a physiological course. The postpartum period was
uneventful. Nursing mothers of the studied group did not have severe somatic diseases,
endocrine disorders and did not receive treatment with hormonal drugs. The volume of
lactation in 48 (82%) women with infants was sufficient and was determined by summing the
sucked and expressed milk during the day. In the colostrum, 27 (47%) women had sufficient
lactation. Breast milk samples were taken in lactating women in the morning (from 9 a.m. to
12 p.m.). Before analysis, the milk was degreased by centrifugation for 15 minutes at 3000
rpm.
We also observed 78 full-term babies born from satisfactory pregnancy and childbirth. The
early neonatal period was uneventful. All children were breastfed. Mixed saliva was taken
from lactating women and their newborns in the morning. Selected aliquots of milk and
saliva were stored at a temperature of 20 ° C until analysis. The concentration of estrone in
breast milk and saliva milk was determined by the enzyme immunoassay using kits of the
DBG company represented by BioChemMak LLC (Russia). Processing of the obtained
material was carried out using the MS Office 2010 software package. To determine the size
of the sample population of the contingent survey, the formula AM was used. Merkova and
L.E. Polyakova. Using the statistical method, the obtained data were grouped, relative
indicators, arithmetic mean and their errors, Student's confidence criterion (t-criterion) were
calculated.
III.
RESULTS
As you know, sex hormones due to the anabolic effect affect the structure of the main
substance of the bone, accelerate the growth and differentiation of the skeleton, and also have
a significant effect on the mineralization of calcified tissues. Acceleration and deceleration of
the growth and development of teeth under the influence of hormonal rearrangements should
be interpreted as a hormone-dependent process (E.I. Goncharova, 1976). For oxytocin,
prolactin, estradiol, and estrone, various mechanisms to different degrees can occur. The
prevalence of any of them apparently reflects the degree of participation of this maternal
hormone in the regulation of certain functions in the infant. In this regard, it is necessary to
study and concretize the metabolic pathways of these hormones and having this kind of
information, you can determine which hormone and at what concentration should be
introduced into the composition of artificial nutritional mixtures. Unfortunately, the
experimental data on the fate of "milk" hormones in the div of newborns is extremely small,
which is associated with methodological difficulties. However, our results of studies on the
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hormonal composition of human milk, mixed saliva of a newborn in comparison with the
hormonal status of lactating women with obesity will allow us to determine the role of the
hormone aspiring for a priority study. In this paper, we examined the dynamics of one estrone
hormone in various substrates in lactating women with normal and overweight. It is known
that biotransformation of estradiol or conversion to a less active estrone occurs with the
participation of the enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) (the process is
reversible). Enhanced capture of estrone from the circulation, and to a lesser extent estradiol,
as can be seen from the presented research results, the table is accompanied by an increase in
the concentration of estrone in breast milk in lactating women with normal div weight,
where the concentration of estrone was 5.97 ± 0.54 nmol / l An interesting fact was noted in
lactating women with overweight. In this situation, the level of estrone in breast milk
averaged 2.04 ± 0.12 nmol / L, which is 2.9 times lower than the rates of women with normal
div weight. Thus, an interesting fact, a change in the level of estrone in breast milk in
dynamics, lactation, which, in our opinion, is associated with postpartum hormonal changes
in the mother’s div, is noted. But these changes have a peculiar dynamics regarding the fat
metabolism of puerperas. T.V. Chepurnoy (1992), studying the content of estradiol in breast
milk and in the blood plasma of newborn babies, showed that in the first week after childbirth
there is a regular elimination of this hormone from the div of both mother and baby. As for
estrone, its level in human milk was high enough and did not show a tendency to decrease in
the dynamics of the postpartum period, as is the case for other estrogens. A similar dynamics
was noted in our studies, but in contrast to its results, different dynamics were observed in
women with excess div weight. Therefore, depending on the physiological state of the
lactating woman, the newborn receives estrone in various concentrations in a biologically
active form. The further fate of maternal hormone in the div of a newborn can theoretically
be presented from at least three perspectives: inactivation of the hormone in the intestine due
to enzymatic cleavage, the effect on the maturation of the receptor apparatus of enterocents,
cells of the diffuse endocrine system of the intestine and epithelium of the oral mucosa for the
development of the dentition.
Table 1. The content of estrone in various fluids of lactating women and their newborns
Indicators
Lactating women
Non obese patients
Overweight (<25 kg / m2.)
Body mass index
<30.0 kg / m2
Obese patients
Overweight (> 25.0 kg /
m2.)
Body Mass Index> 30.0
kg / m2
Breast milk (nMol / L)
5,97±0,54
2,04±0,12*
Mixed Saliva (nMol / L)
642,05±11,23
327,01±10,54 *
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The blood plasma of the newborn on the
8th day after birth (nMol / l)
7,84± 0,61
3,15± 0,24*
Mixed saliva of a newborn 6 months
(nMol / L)
0,89±0,07
0,24±0,02*
Mixed saliva of a newborn 8 months
(nMol / L)
1,17±0,12
0,56±0,09*
Mixed saliva of a newborn 10 months
(nMol / L)
2,01±0,23
0,98±0,11*
Note: * - significance of differences P <0.05
The content of estrone in breast milk and mixed saliva of lactating women
Non obese patients
Obese patients
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Breast milk (nMol / L)
Mixed Saliva (nMol / L)
Non obese patients
Obese patients
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The content of estrone in the mixed saliva of newborns.
Studies by E.I. Goncharova (1978) and Zueva T.E. (2003) indicated that the acceleration and
deceleration of tooth growth and development under the influence of hormonal changes
should be interpreted as a hormone-dependent process. It was found that the developing
tissues of the tooth are sensitive to hormonal changes, and the degree of change depended on
the dose and type of hormone.
As you know, the concentration of steroid hormones in saliva reflect unconjugated, which
means biologically active fractions of hormones. At the same time, collecting samples of
saliva in this case is not difficult, which causes great interest of researchers in
salivodiagnostics. However, clinical studies of the prognostic value of hormones in saliva are
contradictory. Based on the foregoing, at the next stage of research, we analyzed the features
of the hormonal status in saliva in lactating women. As can be seen from the presented
research results, in women without obesity, the estrone content in mixed saliva was 2 times
higher than the level of women with overweight. It is not excluded that high estrone in mixed
saliva of lactating women is associated with the loss of the hormone not only in blood but
also in saliva. On the other hand, this condition can be explained by a change not only in the
hormonal state, but also in the state of the dentofacial system, on which hormones have a
direct effect. As indicated above, in the early stages after childbirth, there is a natural
elimination of hormones from the div of both the mother and the baby. It is with this that
the high values of the hormone in the blood plasma of the newborn are probably connected,
as indicated in the table. But at the same time, an interesting fact is that in children from
women with overweight there is a decrease in the level of estrone in blood plasma by an
average of 2.5 times.
0
1
2
3
4
5
6
7
8
The blood plasma of the newborn on the 8th day
after birth (nMol / l)
Mixed saliva of a newborn 6 months. (nMol / L)
Mixed saliva of a newborn 8 months. (nMol / L)
Indicators of mixed saliva in children
Obese patients
Non obese patients
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Our next task was to study the estrone content in the saliva of a newborn at different times of
teething. The reason for this was the fact that sex hormones, due to the anabolic effect, can
affect the structure of the main substance of the bone, accelerate the growth and
differentiation of the skeleton, and also have a significant effect on the mineralization of
calcified tissues. As can be seen from the presented research results, an increase in the
concentration of estrone in the saliva of newborns at various times of the neonatal period was
noted. So, if by the 6th month of breastfeeding, the concentration of estrone in saliva was
0.89 ± 0.07 nmol / L, then by the 8th month of the study it increased to 2.01 ± 0.23 nmol / L,
which is 2.3 times above the original values. The same dynamics could be observed in the
saliva of newborn babies from lactating women with excess div weight, but at a lower level.
The low levels of estrone in saliva in children who are fed excess weight by mothers are
apparently due to the ratio of positive and negative effects, which is determined by age, type
of distribution of fatty tissue, severity of obesity, etc. Thus, a comparative study of the
concentration of hormones in blood plasma and saliva of newborns and in breast milk showed
that a child with mother’s milk receives high estrone subsidies, which plays an important role
in the development of the newborn’s dentition.
IV.
DISCUSSION
Thus, in newborns in the neonatal period, changes occur in the hormonal system, which is
closely interconnected with the dynamics of the hormonal status of lactating women. At the
same time, the process of lactation and the dynamics of steroid hormones in blood plasma
and saliva are closely related to the state of metabolic processes in the puerperas, i.e.
associated with the restructuring of the entire complex hormonal system with its feedbacks.
It was found that the developing tissues of the tooth are sensitive to hormonal changes, and
the degree of change depends on the dose and type of hormone, in particular estrone. Slowing
of teething is accompanied by a certain morphological rearrangement, or an increase in the
cartilage zone with a slowdown in the bone formation process, or a decrease in the size of the
cartilage plate with significant activation of bone formation. At the same time, acceleration
and deceleration of the growth and development of teeth in a newborn under the influence of
hormonal changes occurring in lactating women should be interpreted as a hormone-
dependent process.
Obesity, of course, is associated with a weakening of methylation reactions due to the
development of liver steatosis and possibly through a violation of the adipokine regulation of
the enzyme catechol-O-methyltransferase (COMT) activity, the synthesis and activity of
which is encoded by the COMT gene located on chromosome 22q11 (28). that estrogens,
along with other steroids, are modulators of lipolysis processes through various types of
estrogen receptors (ERα, ERβ1 – ERβ5). Estrogens selectively affect the activity of hormone-
sensitive lipase by regulating the density of adrenergic receptors in fat depots of various
topographical affiliations. An increase in the total mass of adipose tissue always entails a
change in the div's need for the expression of the COMT gene. In lactating women with
obesity in the event of COMT failure and incomplete estrone synthesis, there is a risk of an
additional increase in the occurrence of dentoalveolar anomalies. Therefore, the question of
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the role of COMT gene expression in the presence of obesity in lactating women as a
predictor of teething disorders in a newborn remains open.
Adipose tissue is one of the main "targets" of steroid hormones; at the same time, adipocytes
are able to accumulate, metabolize and synthesize these hormones. The postpartum period in
women, especially overweight, is accompanied, in our opinion, by a change in fat and
carbohydrate balance with the development of resistance to insulin and leptin. Estrone
deficiency causes a reduction in the energy needs of the div as a whole, and creates an
additional risk of negative metabolic effects.
It should be noted that the results of this study can be used in the development of new
adapted milk mixtures for artificial feeding with the inclusion of a number of hormones in
their composition. Correction of milk nutrient mixtures with biologically active hormonal
additives will allow for more rational artificial feeding of infants due to the maximum
approximation of the formula of the mixtures to the composition and properties of human
milk.
V.
CONCLUSION
1. In healthy lactating women, breast milk contains hormone-estrone in fairly high
concentrations. Meanwhile, the hormonal profile in a newborn in saliva with metabolism in
lactating women may undergo certain changes.
2. As lactation develops in women with excess div weight, hormone estrone undergo
intensive elimination from milk, which leads to a decrease in its content in breast milk and
can be reflected in the metabolic processes of the newborn’s dentofacial system.
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