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embryo3.gif (13360 bytes) EARLY PREGNANCY:
Biology and Medicine

Editor-in-Chief: Eytan R. Barnea MD, FACOG

October 2000
Volume IV, Number 4
ISSN: 1537-6583
Pages: 219-229

R.Klimek

 

 


Enzymes: The Most Important Markers Of Pregnancy Development*

Rudolf Klimek

Chair and Department of Endocrinology and Fertility, Jagiellonian University, Kopernika 23, Cracow, Poland, Fax number: 0048-12-4213666


Key words: enzymes, oxytocinase, isooxytocinase, pregnancy monitoring


Abstract

From ethical and moral reasons, the progress in neonatology and anesthesiology must not obscure the iatrogenic labors, which begin at the time improper for individual child, especially after induction and - because of that - very often instrumental. Enzymatic monitoring has enabled reduction of the number of preterm and instrumental deliveries, and - more importantly - the elimination of statistical (so--called post-datism) indications for terminating pregnancies instead of natural their individual occurrence in the entire range of physiological norm of human labors from 370/7 to 432/7 weeks. During pregnancy the mother’s organism has to secure a proper environment for the growth and development of the child, which is accompanied by the constant increase in oxytocinase and isoxytocinase. These enzymes are closely connected even with the regulation of ovulation as well as with the embryo nidation and development of early pregnancy. Both enzymes are very important indicator of the threatened life and health of the fetus. It is important since these changes precede clinical symptoms by several weeks. On the other hand, they enable monitoring of the efficiency of ACTH depot therapy as well as pregnancy complicated by diabetes, hypertension and endocrinopathies. The values of prenatal oxytocinasaemia make possible prediction the date and course of delivery. Also, they are highly positively correlated with the weight, length and maturity of the newborn, as well as the size of the placenta. In multifetal pregnancies, levels of both enzymes are higher than in single ones.

Mystery of life
The mystery of human life is viewed in different categories: philosophical, religious and scientific. They all agree on the most important point, i.e. that life does not originate de novo but is transmitted by way of fusion of two cells. From conception through possible birth to inevitable death, the newly created being does not change its singular identity, while remaining as a whole in the states of thermodynamic equilibrium, close to them, and ceding from them constantly to the most distant point, which is equivalent to death. Contemporary physics names the set of those states ”thermodynamic branch”, which ends in the so-called “bifurcation point”, beyond which the system can not exist (Fig.1). Every system is made up of microsystems and relations between them, while those components also have their own thermodynamic branches. There is, however, a fundamental difference between every living cell and the human being, although both have their own thermodynamic branches ending in bifurcation point, which is the environment they adjoin with their surfaces (Fig.2).

Every cell exists and operates only in the biological environment, which is the rest of human organism, whose environment in turn is not biological. Furthermore, in relation to this environment human being remains in the state distant from the equilibrium, because thus man can exchange the mass and energy with the environment which is an indispensable condition of its existence and development, while cells between themselves remain in the state of equilibrium due to the causative action of life: they simply all live. Nevertheless all the time many of them meet with sudden or programmed death in order to enable the whole organism to continue. Others only divide into descendant cells, i.e. they pass on life.

Unfortunately, it happens - and not rarely - that for internal or external reasons some cells remain long in the state distant from the equilibrium with the rest of the cells. To avoid death in their bifurcation point they have to reorganize themselves out of their constituent parts, so as to preserve their own life (existence!). Yet in accordance with the laws of nature there must appear an entirely new cell with new identity. This new identity lies in the fact, that in hostile environment, by dint of a better organization of life, (i.e. smaller production of entropy) dissipation of matter and energy in the environment should be increase. We know this as a natural process of cancerogenesis leading to the neoplastic disease and death of the entire organism (1-4). Cancer has its singular biological identity stochastically conditioned by self-organization in biological environment composed of host cells which have the common identity. Among the last ones, there are also reproductive cells, which in pathologic states (far from equilibrium) can also be the starting point of neogenesis. In physiological conditions, however, it is only after the union with the corresponding cell of the sexual partner (with the different identity) they give rise to a new human being with their own identity from the very outset. Only a system like this, after reaching the successive developmental stages, can naturally exist, develop and operate.

Levels of human cognition
The demonstrated complexity of possible relations between cells and the multicellular organism corresponds also with the relation between cells and their cellular microsystems. On this level, the question of understanding the essence of life becomes complicated due to direct presence of single atoms and ions, which consequently we also have to consider as microsystems, although being positive that they are inanimate structures, just as any other non-organic or organic chemical compound which makes up a cell.

In 1828 (50 years before the discovery of microbes) the synthesis of urea was considered a great achievement of science, since in the nineteenth century urea was known only as a natural product of living organisms. 1954 was the year of synthesization of peptide hormone oxytocin, which is generally seen as a biochemical compound only because it is composed of amino acids, which form natural proteins. Similarly, all steroid hormones as well as thyroxine and triiodothyronine, which also are only organic compounds, are prefixed “bio“, which should denote only the presence of the life component in these structures (Table1). Hence, a vital question comes up: when does life appear between the level of atoms and ions, and that of cells and organisms? Life whose sense we usually express descriptively.

The essence of life manifests itself in a biological system’s ability to: (1) grow, (2) reproduce, (3) metabolize matter and energy, (4) react to stimuli, and (5) move. Each of these features makes one aware of its inherent connection with time. It is this imaginary time that I named “alter ego of life”, whose manifestation describes the prefix “bio”. The natural structural proteins and enzymes are an example of the simplest forms of the existence of imaginary time in those space-time structures. They cannot move nor reproduce alone but their existence is conditioned by their being part of the animate world. There is a notable qualitative difference between the molecules of oxytocin (chemical compound level) and of oxytocinases (biochemical level), both made up of the same atoms (on the physical level). Denaturated oxytocinase becomes a solely chemical compound, since it lost its mysterious “bio-“ component (i.e. life), which is colloquially dubbed “natural protein”. Also, a sperm cell and oocyte cannot continue to grow or reproduce alone, although there is no doubt that they belong to the animate nature but not at the level of mature organisms, i.e. those that are characterized by all five above-mentioned features relevant to self-dependent life.

Oxytocinase as a biomarker
Zygote is an ideal example of the essence of life, which in its “bio” part is passed from generation to generation. The above discussion leads to the conclusion that the compounds which definitely have the life component are enzymes. It means that living organism as a whole participates in their biosynthesis. Thus, by examining their concentration in systemic fluids we evaluate not only the substrates which appear or disappear because of them (e.g. blood levels of oxytocin, corticoreline, ACTH, estriol, etc.) but – principally – we immediately evaluate the condition of organism on the most important level of the life (Table 1).

In the time-spatial process of pregnancy, placenta plays exceptional role. Time of its existence coincides with maturation of fetus. Therefore, the oxytocinase produced by the placenta becomes the most important biological marker (5-9). Not only does it connect with the mother’s and the fetus’s neurohormones, which induce its production, but its production is also directly dependant on the time-spatial structure and function of the placenta, whose enzymes are the most important biomarkers.

During pregnancy the mother’s organism has to secure a proper environment for the growth and development of the child, which is accompanied by the constant increase in oxytocinase and isoxytocinase (Fig. 3 and 4). These enzymes are closely connected even with the regulation of ovulation as well as with the embryo nidation and development of early pregnancy. Irrespective of their role in the entire neuroendocrinological regulation between mother, fetus and placenta, low or prematurely decreasing level of both enzymes is a very important indicator of the threatened life and health of the fetus. It is important since these changes precede clinical symptoms by several weeks. On the other hand, they enable monitoring of the efficiency of ACTH depot therapy (Fig 5 and 6), as well as pregnancy complicated by diabetes, hypertension and endocrinopathies. The values of prenatal oxytocinasaemia make possible prediction the date and course of delivery. Also, they are highly positively correlated with the weight, length and maturity of the newborn, as well as the size of the placenta. In multifetal pregnancies, levels of both enzymes are higher than in single ones.

Pregnant women with the low levels of oxyticinase more often need induction and stimulation of labor, as well as being threatened by intra- and post-partum hemorrhages, lack and shortening of lactation, and - in the future - by cervical cancer. This way, an obstetrician receives important information about the condition of the mother’s whole organism.

For 40 years, enzymatic monitoring has enabled reduction of the number of preterm and instrumental deliveries, and - more importantly - the elimination of statistical (so--called post-datism) indications for terminating pregnancies instead of natural their individual occurrence in the entire range of physiological norm of human labors from 370/7 to 432/7 weeks. Besides, enzymatic monitoring is a part of computer-aided monitoring of pregnancy and birth term prognosis owing to the quantization of maturity and formulation of modern obstetrical indices of fetal maturity, based on the quantum mechanics and theory of relativity (10-11).

Conclusions

The first enzymes used in medicine were placental defensive enzymes of Abderhalden. Nowadays, it is difficult to imagine many domains of medicine without enzymatic diagnostics and monitoring of therapy. Despite the great role of oxytocinase and its well-documented practical clinical significance, there is an incomprehensible barrier in the mentality of gynecologists, who are willing to embrace new technological inventions and physical methods, although there are more and more voices stressing the need to break with the “ethics of silence” on useful clinical methods - not understood by many doctors responsible for health and life of every conceived child.

From ethical and moral reasons, the progress in neonatology and anesthesiology must not obscure the iatrogenic labors, which begin at the time improper for individual child, especially after induction and - because of that - very often instrumental. After bringing cardiotocography down to rational dimensions and the re-programming of ultrasonographic biometry, there is a moral imperative to extend the use of cheap, highly repeatable enzymatic exams primarily to restore natural labors in healthy women at least in 90%.

For personal use. Only reproduce with permission from SIEP.


References

Klimek R.: Cervical cancer as a natural phenomenon. Presented at 4th Meeting E.A.G.O., Cracow 1989, Eur J Obstet Gynecol Reprod Biol, 1990, 36, 221-238

Klimek R.: Casual prevention of cancer as a natural biological phenomenon. Medicine Biologie Environment. 1990, 18, 8. CP11

Klimek R.: Apoptosis in terms of subcellular self-organization of cancer as a new dissipative structure. The INEC European Institute of Ecology and Cancer, Pavia, Italy, 1993, Book of abstr. 11; Medicine Biologie Environnement, Forni E., Santamaria L. (eds), 1994, 22, 2, 571-575

Klimek R.: Conquering cancer ourselves. New trends in gynecology and obstetrics. J.Libbey CIC s.r.l., Roma, 1990, Vol. VI, No 2, 53

Klimek R., Bieniasz A.: Studies on the relation between serum oxytocinase and labor. Am. J. Obst. Gynec., 1969, 104, 959 

Klimek R., Drewniak K., Bieniasz A.: Further studies on the oxytocin-oxytocinase system. Am. J. Obstet. Gynec., 1969, 105, 427

Klimek R., Fedor-Freybergh P., Janus L., Walas-Skolicka E.: A Time to Be Born. DREAM Publishing Company, Inc. Cracow, 1996

Klimek R.: Pietrzycka M.:Biochemische Methode zur Bestimmung der Oxytocinase und Klinische Bewertung. (Biochemical method for the determination of oxytocinase and its clinical value). Clin Chim Acta, 1961, 6, 326

Klimek R.: Enzymes as the most important obstetrical markers. In: Seminars in Perinatal Medicine-Evaluation of selected enzymes in pregnancy monitoring. R.Klimek, G.Breborowicz (ed), Poznan, 1999, II,9-22

Klimek M.: Computer aided imaging in advanced pregnancy. In: Popkin D.R. and Peddle L.J. (eds) Women’s Health Today, 245-250. Parthenon, New York, London

Klimek M.: Medical prognosis versus statistical prediction of birth term. W: Klimek R., Fedor-Freybergh P., Janus L., Walas-Skolicka E.: A Time to Be Born. DREAM Publishing Company, Inc., Cracow 1996


Table 1
Levels of human cognition

Level of cognition

Examples

Physical: atoms and ions

02, H+, Cl-, measurement of pregnancy duration and fetal size

Chemical: organic and no organic compounds

H20, NO, CO2, oxytocin, steroids

Biochemical: biochemical compounds

Enzymes, gonadotrophins, structural proteins

Biophysical: biophysical processes

Maturation, development,

biometry of fetal growth

Humanistic: man

Ideas, emotions, speech, notions


Fig. 1
Thermodynamic branch of biological system

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Fig. 2
Thermodynamic notions for organism and cell

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Fig. 3
Values of oxytocinase and isooxytocinase according to biological age

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Fig. 4
Values of oxytocinase and isooxytocinase according to calendar age

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Fig. 5
Enzyamtic monitoring of ACTH depot (A) therapy

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Fig. 6
Enzymatic monitoring of ACTH (A) therapy

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