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Cocarboxylase, vitamin B2 and lipoic acid in obstetric and gynecological practice

In recent years, against the background of a sharp decline in the birth rate in Moscow, there has been a significant increase in the frequency of perinatal pathology (1.5–2 times), a stabilization in the frequency and birth of premature babies (7–9%). There is a certain pathomorphism of diseases of the newborn period, pathogenetically associated with the deterioration of the health status of mothers. Most diseases in children are characterized by multisystem disorders, neurosomatic disorders, occurring against the background of significantly reduced resistance in the reparative period of diseases such as perinatal encephalopathy, sepsis, pneumonia, and respiratory distress syndrome. Most children experience persistent dysfunction of various organs and systems, and develop disadaptation syndrome (syndrome of increased excitability, dysbacteriosis, dyskinesia of the gastrointestinal tract, allergic reactions, prolonged and recurrent acute respiratory viral infections).

There is a direct relationship between the cytochemical parameters of a pregnant woman and the histochemical parameters of the developing fetus. Indicators of the enzyme status of a woman’s lymphocytes at 7–10 weeks are prognostically significant for assessing the state of energy metabolism in a developing child throughout pregnancy. No less important is dynamic monitoring of the state of energy metabolism in children of different ages, especially in newborns and children in the first year of life. Changes in the energy metabolism of brain cells, cardiomyocytes, and epithelial cells of the intestinal mucosa in a newborn child who has suffered chronic antenatal or acute intrapartum hypoxia lead to the formation of dysfunctions of the above organs, which disrupts the adaptation processes of the newborn child. Timely prescribed effective metabolite therapy allows you to correct disorders of cellular energy metabolism and prevent the development of such dysfunctions.

Monitoring the state of energy metabolism in a pregnant woman makes it possible to promptly detect fetal tissue hypoxia and take timely measures to correct it.

At the moment, a large amount of clinical material has been accumulated on the use of various metabolic therapy regimens, prescribed depending on the parameters of cytochemical blood tests and underlying the prevention of the development of pregnancy pathologies. The use of these schemes in preparation for pregnancy and during it allows optimizing energy exchange processes and reduces the risk of perinatal pathology in the unborn child.

The totality of identified cytochemical changes determines the direction of metabolite therapy. Currently, based on cytochemical studies of energy metabolism, a number of combined drugs with metabolic action have been developed. In particular, at low levels of activity of mitochondrial flavoproteins, the use of cofactors of the tricarboxylic acid cycle is justified. However, it is known that parenteral administration of metabolite drugs is more effective than enteral administration, and this sharply limits the use of these drugs in outpatient practice. As an alternative to the parenteral route of administration, metabolic complexes in the form of suppositories are offered. The bioavailability of drugs with this route of administration increases significantly and is not inferior in terms of effectiveness to that observed with the parenteral route of administration. When developing such complexes, the main attention is paid to the synergism of the action of drugs in the correction of biochemical processes in the cell.

As you know, all food products in the body are broken down into acetyl-CoA, which enters the final oxidation pathway - the tricarboxylic acid cycle. Activation of the di- and tricarboxylic acid cycle is possible by regulating two important stages: 1) oxidation of pyruvic acid to acetyl-CoA and then interaction with oxaloacetate to form citric acid; 2) oxidation of ketoglutaric acid to succinate (succinic acid). Both of these steps can be catalyzed by the Corylip multienzyme complex, which includes lipoic acid, cocarboxylase and riboflavin.

Materials and methods

Research by the Research Institute of Pediatrics together with the Center for Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences, with the Moscow Antiherpetic Center and with the 25th Maternity Hospital in Moscow with the participation of 64 women at risk and their children, observed for a year after birth, proved how important the use of energy-normalizing drugs is actions in women preparing for pregnancy and in pregnant women.

Korilip suppositories were used as part of basic therapy in 31 women during pregnancy under the mandatory control of quantitative cytochemical analysis. Only basic therapy was also received by 33 women in the comparison group. The enzymatic status of peripheral blood lymphocytes was studied in the classic version of the reaction (R.P. Nartsissov, 1969–1984), including determination of the activity of succinate dehydrogenase (SDH) and glycerophosphate dehydrogenase (GPDH), as well as in various modifications of the classic version, allowing to assess membrane permeability and stability of the mitochondrial locus containing succinate dehydrogenase. The permeability of the mitochondrial membrane was indirectly assessed by SDH activity after 10 min of incubation. It was assumed that the rate of formation of the reaction product when detecting SDH activity is maximum in the first minutes of exposure and minimum at an exposure time of 60 minutes.

This method made it possible to determine not only the average activity of the enzyme, as is done in biochemical studies, but also made it possible to consider as characteristics the parameters of the distribution of cells by enzyme activity - coefficients of the second, third and fourth order (coefficients of variation, asymmetry, kurtosis), as well as a measure cellular diversity (relative entropy of information). The totality of these distribution parameters according to enzyme activity constitutes the concept of the enzyme status of blood cells. Thus, analysis of the cell population made it possible to identify changes in various cell subpopulations against the background of still unchanged average activity, since these changes in cellular structure appear before the clinical signs of the disease.

To assess the functional activity of mitochondria, a cytomorphodensitometric method was used to determine SDH activity. Analysis of the functional activity of mitochondria based on cytomorphodensitometric parameters made it possible to identify the features of the pathological process at the subcellular level and evaluate the effectiveness of the treatment.

results

It was found that in pregnant women at risk who received a course of treatment with the Korilip complex against the background of basic therapy, the frequency of pregnancy complications with repeated acute respiratory viral infections was 2.5 times lower compared to the comparison group. They were less likely to experience exacerbations of chronic foci of infection. Hypochromic anemia in pregnant women was diagnosed 2.9 times less often in those receiving Corilip. The most effective use of Korilip in relation to the child was observed in women who received therapy 6–9 months before and during pregnancy. Early use of the drug ensured that the development of perinatal complications was minimized and contributed to better development of children in the first year of life by providing a higher level of energy to the tissues and cells of a pregnant woman, newborns and infants.

It was found that during pregnancy the prescription of metabolic benefits is more justified in critical periods (according to cytochemical indicators): 5–8 weeks, 10–12 weeks, 20th week, 27–28 weeks, 30–32 weeks, 35–37 weeks, and especially women at high risk of developing perinatal pathology in children. In women at high risk of developing perinatal pathology in children, as a rule, there is a decrease in the activity of SDH and alpha-GPDH against the background of deformation of the population structure in the form of a reduced number of lymphocytes with typical activity (kurtosis less than –0.8). For them, the prescription of the Korilip complex is justified, both as an independent treatment and in combination with specialized therapy. As a rule, at least 6–8 courses of 10 days with the Korilip complex are necessary to normalize the enzyme status and well-being of a woman.

The choice of course duration (10 days) is explained by the fact that 4–5 days after the start of taking the drugs, there is a positive trend in the cytochemical status of leukocytes, which consists, in particular, in an increase in the average activity of SDH and alpha-GPDH and a tendency towards normalization of other elements of the population structure . The number of courses prescribed is determined by the positive dynamics of cytochemical parameters and the stability of their changes. As a rule, at least 6–8 courses of the Korilip complex are necessary to normalize the enzyme status and well-being of a woman (Fig.).

To study the degree of tension in energy metabolism in response to the administration of the Korilip suppository complex, a test with isocitrate, SDH (IZO) was used (M. N. Kondrashova et al., 1987; S. V. Petrichuk et al., 1990). It is known that in response to the action of an intense external stimulus, there is a sharp increase in the production of energy resources in the cells of the body, which are used to ensure a response. To prevent excessive consumption of energy cycle substrates and depletion of mitochondrial activity, there is a protective mechanism by blocking the main mitochondrial enzyme, succinate dehydrogenase. This block is inactivated during a reaction to detect SDH activity with the addition of isocitric acid to the main substrate. An increase in enzyme activity in a sample with isocitric acid, compared to a sample on the main substrate, indicates an increase in energy metabolism. To assess the degree of tension in energy metabolism, the coefficient K is calculated:

K = SDH (ISO)/SDG = 1.15 or 115%

The value of the coefficient K > 1 is an unfavorable cytochemical sign, indicating the stress of cellular metabolism and the instability of the mitochondrial membrane. In relatively healthy patients, the K coefficient is 80–90%.

It has been proven that during treatment with Korilip suppositories, the value of the K coefficient decreases and approaches normal values ().

conclusions

The most effective use of Korilip in relation to the child is observed in women receiving therapy 6–9 months before and during pregnancy under the control of cytochemical analysis.
The duration of courses of therapy with the Korilip complex (10 days) and their frequency are determined by the activity of peripheral blood leukocyte enzymes.
During pregnancy, it is justified to prescribe metabolic benefits during critical periods (according to cytochemical indicators): 5–8 weeks, 10–12 weeks, 20th week, 27–28 weeks, 30–32 weeks, 35–37 weeks.
Preparing a married couple for pregnancy should begin at least 6–9 months before pregnancy; optimally, the year of life of the parents before conception should be attributed to the ontogenesis of the child.
Metabolite correction of energy metabolism disorders in women should be the first step of medical care. It represents the most physiological medication that allows, in most cases, to increase the effectiveness of any basic treatment, and in some cases to avoid it.

Literature

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Zh. Kh. Kushkhova , Candidate of Medical Sciences

GP No. 153 UZ NEAD , Moscow

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