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Vol 30, No 4/5 (2023)

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Reviews

Modern studies of the effectiveness and safety of methods for the prevention of preterm birth

Gabitova N.A., Kedrova A.G., Dikke G.B., Belousova T.N., Malysheva O.G.

Abstract

The problem of saving every desired pregnancy is relevant in our country due to the difficult demographic situation. Preterm morta-lity rates remain high. Data from studies on the prevention of preterm birth (PB) by administration of progesterone to women with risk factors (history of PB, short cervix, multiple pregnancies) are heterogeneous. Vaginal administration of micronized progesterone is preferred. Cerclage has shown an effect only in singleton pregnancies with previous spontaneous PB in combination with a short cervix. There is no evidence for prophylactic cerclage in multiple pregnancies, even in cases of short cervix. An emergency cerclage remains an indication after an individual consultation. The effect of the cervical pessary in singleton and multiple pregnancies in patients at risk of preterm birth appears to be promising compared to other secondary prevention options when therapy is initiated at the early stages of precocious cervical ripening. Approaches related to nutrition and the intake of dietary supplements for the prevention of PB (zinc, vitamin D, docosahexaenoic acid) are promising/ Smoking cessation before pregnancy is an effective measure to prevent PB. Conclusion. Decisions in favor of choosing one or another method of prevention of PB should be made individually in each case.

Pharmateca. 2023;30(4/5):8-15
pages 8-15 views

The role of choline in epigenetic programming of somatic and mental health during fetal development and prevention of obstetric complications

Tapilskaya N.I., Zhernakova T.S., Bespalova O.N., Ryzhov Y.R., Glushakov R.I.

Abstract

The metabolism of choline and its metabolites plays one of the key roles in embryogenesis: phosphatidylcholine is a component of the cell membrane, acetylcholine plays the role of a neurotransmitter, betaine is involved in the metabolism of homocysteine, and dimethylglycine is involved in the processes of mitochondrial respiration. Choline deficiency can cause liver, kidney, pancreatic dysfunction and cognitive impairment. It has been shown that an increase in the choline content in the diet of pregnant women leads to an increase in the cognitive abilities of offspring, which is associated with the normalization of DNA methylation processes. It has been found that only 1 out of 11 pregnant women receives the required amount of choline from food, so an additional 550 mg of choline daily is recommended for pregnant women.

Pharmateca. 2023;30(4/5):16-22
pages 16-22 views

Mechanisms of development of endothelial dysfunction in kidney pathology in children

Yarovaya D.V., Bashkina O.A., Pakhnova L.R.

Abstract

Currently, endothelial dysfunction (ED) is considered as an integral part of the pathogenesis of many chronic diseases. The endothelium is involved in leukocyte recruitment, permeability modulation, inflammation, coagulation, and changes in blood flow in response to disease progression or regression. The kidneys contain different types of endothelium, each with its own specific structural and functional characteristics, as well as being protected by thrombosis, inflammation, and complement regulators. Endothelial damage induced by antibodies, immune cells, or inflammatory cytokines can lead to acute or chronic kidney injury. The relevance of studying the mechanisms of ED in renal pathology is determined by the need to develop new therapeutic strategies aimed at preserving the function of the endothelium and improving the prognosis of the disease. The article provides data on the significance of ED in various kidney pathologies in children, including associated with the result of direct infection with SARS-CoV-2. The analysis included a collection of studies published in PubMed, ProQuest, GoogleScholar, Cochrane, ScienceDirect, Medline, AMED, EMBASE, CINHAL, SportDiscus, Scopus, and eLibrary for 2002–2022.

Pharmateca. 2023;30(4/5):23-27
pages 23-27 views

Clinical experience

Prospects for the use of metronidazole+miconazole in the treatment of mixed vaginal infections

Kulikov I.A., Apolikhina I.A.

Abstract

The review presents the prospects for the use of a combination of metronidazole and miconazole in the treatment of mixed vaginal infections with an emphasis on the most common pathogens of this pathology and possible complications that occur against the background of monocomponent therapy regimens. Taking into account intravaginal use, the mechanism of the pharmacological action of medicinal components that are part of combined preparations is discussed. The pharmacodynamic and pharmacokinetic mechanisms of action of metronidazole and miconazole are analyzed.

Pharmateca. 2023;30(4/5):28-33
pages 28-33 views

Postoperative ileus in gynecological practice: a simple, effective and safe solution to the problem

Trukhan D.I., Degovtsov E.N., Degovtsova E.A.

Abstract

Abdominal surgery can cause development of dynamic intestinal obstruction, so called postoperative ileus. The incidence of postoperative ileus (POI) after gynecological surgery averages 10–15% (range 5–25%). Chewing gum (CG) has been used in abdominal surgery and obstetric and gynecological practice to reduce POI since the beginning of the 21st century. In obstetrical and gynecological practice, the largest number of randomized clinical trials and meta-analyses are devoted to the use of CG after caesarean section. The present review discussses the main randomized clinical trials, reviews and meta-analyses devoted to the study of the effect of CG after other surgical interventions in gynecological practice for the prevention of POI. The data presented in the review indicate the effectiveness and safety of the use of CG in the postoperative period for the prevention of POI in gynecological practice.

Pharmateca. 2023;30(4/5):34-38
pages 34-38 views

New drugs end treatment approaches

Efficacy of intraovarian administration of platelet-rich plasma in infertility treatment programs using assisted reproductive technologies

Fortygina Y.A., Kulakova E.V., Makarova N.P., Teterina T.A., Apolikhina I.A., Kalinina E.A.

Abstract

Background. Current trends in delayed motherhood dictate the search for new solutions to maintain women’s reproductive health. An increase in the average age of primiparas up to 30–40 years is unshakably accompanied by physiological aging of the ovaries and, accordingly, a decrease in the quality and number of germ cells.

Material and methods. The article highlights the results of the introduction of autologous platelet-rich plasma into the ovary. The analysis of clinical and anamnestic characteristics of patients, hormonal profile and the effectiveness of the procedure in preparation for in vitro fertilization programs was carried out.

Conclusion. The effectiveness of the autologous administration of platelet-rich plasma opens up new opportunities for patients with reduced ovarian reserve and certain hormonal profile parameters, but further research is required in this area.

Pharmateca. 2023;30(4/5):39-42
pages 39-42 views

Original articles

Clinical efficacy of dynamic quadripolar radiofrequency therapy in postmenopausal women with vulvovaginal atrophy

Kazakova S.N., Apolikhina I.A., Teterina T.A., Makarova L.N.

Abstract

Background: Vulvovaginal atrophy (VVA) is a chronic progressive disease that affects the female genital organs and lower urinary tract. This condition is associated with hypoestrogenia as a result of menopause, but can also develop in patients suffering from breast cancer after adjuvant hormonal therapy. Given the high prevalence of VVA and the expected increase in its incidence, and due to the increase in the mean age of women, it is easy to understand its significant social impact. VVA causes unpleasant disorders such as vaginal dryness, itching, burning, and dyspareunia, and requires ongoing treatment – when the therapy is stopped, the symptoms usually reappear. Currently available treatments include vaginal lubricants and moisturizers, vaginal estrogens and dehydroepiandrosterone (DHEA), and systemic hormone therapy. However, since these treatments have contraindications, lack of efficacy, and poor adherence to treatment, search for innovative, effective, and safe treatments is critical.

Objective. Evaluation of the efficacy and safety of dynamic quadripolar radiofrequency (DQRF™) therapy in the treatment of VVA in postmenopausal women.

Methods. The study included 180 women. The mean age of the patients was 52±4.3 years. All patients underwent a course of treatment: group 1 – the impact of DQRFTM on the vagina and vulva, 4 procedures with an interval of 2 weeks; group 2 – DQRF™ in the mode of radioporation with estriol cream 0.5 mg, 4 procedures with an interval of 2 weeks; group 3 - local hormonal therapy with estriol cream 0.5 mg according to the scheme for 8 weeks. Evaluation of the effectiveness of treatment was carried out by measuring the vaginal pH, assessing the index of vaginal health, FSFI, VSQ questionnaires. In all groups, satisfaction with the appearance of the vulva was assessed according to VAS. For the clinical data of patients in each of the groups, the parameters were compared after treatment with a zero time point using paired and unpaired Mann-Whitney test. Comparison of changes in clinical parameters of the group 1 and 2 with the control group at each time point was made using the Mann-Whitney test.

Results. Analysis of the results of the study revealed a significant decrease in the severity of VVA symptoms one month after treatment in all groups. In the group 1, an increase in the mean vaginal health index in 40 (67%) women from 21.3 to 23.1 points (P<0.001), a decrease in the mean vaginal pH in 39 (65%) women from 6.8 to 4.9 (P<0.001), an increase in mean values of satisfaction with the appearance of the vulva in 48 (80%) patients according to VAS from 6.5 to 9.2 (P<0.001) were observed. In the group 2, there was an increase in the mean index of vaginal health in 50 (87%) women from 18.1 to 24.1 points (P<0.001), a decrease in the mean vaginal pH in 49 (85%) women from 7.0 to 4.5 (P<0.001), an increase in mean values of satisfaction with the appearance of the vulva in 48 (83%) patients according to VAS from 5.5 to 9.0 (P<0.001). Analysis of the results of the group 3 revealed an increase in the mean vaginal health index in 56 (90%) women from 19.1 to 24.5 points (P<0.001), a decrease in the mean vaginal pH in 53 (87%) women from 7.0 to 4.3 (P<0.001), an increase in mean values of satisfaction with the appearance of the vulva in 12 (20%) patients according to VAS from 5.5 to 7.0 (P<0.001).

Conclusion. The article confirms the safety and efficacy of DQRF™ procedures within 12 months of follow-up after the end of treatment sessions. Vaginal health index, vaginal pH, satisfaction with vulvar appearance, and female sexual function index (FSFI) were shown to improve rapidly to near normal levels. It has been shown that it is necessary to undergo a new course of DQRF™ therapy 6–9 months after the previous cycle, and not 9–12 months after, as previously suggested. This algorithm provides maintaining the level of women’s health indicators and quality of life at a high level. This work has shown that it is possible to use only DQRF™ procedures without the use of local hormonal therapy with comparable, and sometimes even superior results. This may be especially true for patients who have had cancer and/or cardiovascular diseases, as well as for patients who refuse hormonal treatment.

Pharmateca. 2023;30(4/5):43-54
pages 43-54 views

Clinical efficacy of multi-dose vaccination against human papillomavirus infection in the Moscow region

Belaya Y.M., Zarochentseva N.V.

Abstract

Background. The effectiveness and safety of modern human papillomavirus (HPV) vaccines have been proven in numerous foreign and domestic studies and are not in doubt. However, the lack of wide coverage of 2 or 3 doses of the vaccine preparation in the world for one reason or another prompted scientists to study the effectiveness of a single-dose vaccination scheme for women of different ages. In our work, we also proved the clinical effectiveness of vaccination of patients who received 1 or 2 doses of HPV vaccine 5–14 years ago.

Objective. Comparison of the clinical efficacy of different HPV immunization regimens in young women who started a vaccination course 5–14 years ago, but for some reason did not continue it, and in patients who received a full vaccination course.

Methods. For the study, anamnestic data and clinical and laboratory research methods were used: clinical picture, PCR (polymerase chain reaction) – diagnosis of HPV of high carcinogenic risk, as well as types 6 and 11 HPV, a cytological method for examining smears from the surface of the cervix and cervical canal and colposcopy.

Results. The data of the study showed that, regardless of the number of doses of vaccines received at a young age, over time, HPV vaccine types were not detected in any of the patients. In the comparison groups, no statistical difference was found in the parameters of cytological and colposcopic examinations. The majority of patients who received one to three doses of the vaccine at a young age had subsequent pregnancies in a natural cycle with a positive outcome with the birth of healthy children.

Conclusion. Regardless of the number of doses of HPV vaccines administered at a young age, there was a positive protective effect from vaccine strains of the virus in the future, which is consistent with world data. Taking into account the opinion of WHO, a change in the approach to vaccination in favor of single- or two-dose immunization regimens, both clinically sound and more cost-effective, is expected in the near future, which is important for increasing coverage of young girls.

Pharmateca. 2023;30(4/5):55-58
pages 55-58 views

Retinol and endometriosis - is everything simple in pathogenesis?

Yarmolinskaya M.I., Seyidova C.I., Tkachenko N.N., Tral T.G.

Abstract

Background. External genital endometriosis (EGE) is a chronic, relapsing, progressive, hormone-dependent disease characterized by a benign growth of tissue outside the uterine cavity, similar in morphological structure and functions to the endometrium. The versatility of the pathogenetic mechanisms of the development of the disease, the variability of clinical symptoms, as well as the lack of a unified concept of endometriosis therapy dictate the need to find modern methods for correcting this pathology. Retinol may be one of these areas.

Objective. Determination of the retinol level of in peripheral blood and peritoneal fluid in patients with EGE, evaluation of the effectiveness of its use on the basis of surgically induced endometriosis in Wistar rats.

Methods. The main group included 38 patients with a histologically confirmed (based on laparoscopy) diagnosis of I-IV stage EGE according to the revised classification of the American Society for Reproductive Medicine (r-ASRM); mean age of patients was 31.7±4.1 years. The control group consisted of 10 patients without endometriosis who underwent diagnostic laparoscopy before entering the protocol of assisted reproductive technologies. Determination of the blood serum and peritoneal fluid vitamin A level in was carried out using Cloud-Clone Corp kits by ELISA.

Experimental model. A surgically induced model of endometriosis was performed on 21 mature female Wistar rats. The creation of the experimental model was carried out in three stages. The first stage was the modeling of the disease, the second was the confirmation of the presence of endometriosis based on laparoscopy and the assessment of the area of endometrioid heterotopias, followed by drug therapy of the disease; the third stage was the removal of animals from the experiment, the assessment of the area of endometrioid heterotopias in dynamics, and histological examination.

Results and discussion. Based on our study, it was found that patients with endometriosis have an increased blood serum vitamin A level, which significantly exceeds its level in the peritoneal fluid by 2 times, especially in the initial forms of the disease. An «artificial» increase in the level of retinol in the blood serum can be mediated by many reasons, primarily by disorders of its metabolism and changes in the retinol-binding protein 4 expression, that justifies the need for further research to study in depth the role of vitamin A in the pathogenesis of endometriosis. At the same time, the high efficiency of the use of retinol, characterized by complete resorption of endometriosis foci based on an experimental model of a surgically induced disease in Wistar rats, makes it possible to consider retinol as a promising method of treating the disease.

Pharmateca. 2023;30(4/5):60-66
pages 60-66 views

Experience with two-stage therapy in the treatment of patients with bacterial vaginosis: long-term results of treatment

Rakhmatullaeva M.M.

Abstract

Background. Modern principles of treatment of bacterial vaginosis (BV) include the use of complex two-stage treatment: the first stage of treatment is the eradication of opportunistic microorganisms and anaerobes; the second stage is the restoration of vaginal pH and normal microflora.

Objective. Determination of the effectiveness of different treatments for BV by assessing the composition of the vaginal microbiota.

Methods. A clinical and laboratory examination of 110 women with BV was carried out, a gynecologic history was analyzed, and the features of extragenital pathology were studied. The patients were divided into 3 groups: group I (38 patients) with severe anaerobic dysbiosis (with predominance of Gardnerella vaginalis) received metronidazole 500 mg orally 2 times a day for 7 days; group II (40 patients) with severe anaerobic dysbiosis (with predominance of obligate anaerobes) – clindamycin for 7 days; group III (32 patients) with severe aerobic-anaerobic dysbiosis – chlorhexidine for 7 days. At the 2nd stage of treatment, prebiotics or probiotics were prescribed depending on the initial number of lactobacilli. The effectiveness was evaluated 1, 3 and 6 months after the treatment, as well as upon presentation of complaints.

Results. The present study proved the importance of determining the composition and quantitative ratio of the vaginal microbiota in BV for the selection of differentiated therapy. Two-stage therapy for BV, selected taking into account the molecular biological variants of vaginal dysbiosis, had a stable treatment effect in 87.3% of cases.

Conclusion. The additional use of prebiotics of the oligosaccharide group as an anti-relapse therapy enhances the colonization of lactobacilli and ensures the stability of the vaginal biotope in 95.4% of cases.

Pharmateca. 2023;30(4/5):67-71
pages 67-71 views

The effect of pregnancy and thyroid hormones on the occurrence and course of extrasystole

Vinogradova O.P., Rakhmatullov F.K., Ostanin M.A., Rakhmatullov R.F.

Abstract

Background. The study of the effect of pregnancy hormones on the occurrence and course of extrasystolic arrhythmia is one of the most difficult issues in modern medicine.

Objective. Evaluation of the effect of chorionic gonadotropin, progesterone, thyroid hormones and type 1 diastolic dysfunction on the occurrence and course of ventricular extrasystole in pregnant women.

Methods. 32 pregnant women with ventricular extrasystole (Group 1) and 30 pregnant women without extrasystole (Group 2) without heart pathology, aged 19–38 years (mean age 29.8±2.4 years) were examined. Research methods included general clinical studies, electrocardiogram (ECG), echocardiography (EchoCG), 24-hour ECG monitoring, determination of the levels of chorionic gonadotropin, progesterone, and thyroid hormones.

Results. A close relationship (p<0.05) between chorionic gonadotropin and thyroid-stimulating hormone levels and extrasystole was revealed. A regression model predicting the course of extrasystolic arrhythmia in pregnant women with AF was constructed. It was found that the predictive value of the equation is 98.6%. The antiarrhythmic effect of the combined use of potassium preparations with magnesium was established.

Pharmateca. 2023;30(4/5):72-78
pages 72-78 views

Changes in the detrusor hyperactivity level with long-term administration of M-anticholinergic

Danilov V.V., Volnykh I.Y., Danilov V.V., Danilov V.V.

Abstract

Background. Detrusor overactivity (DHA) in patients with spinal disease remains an urgent problem due to the high risk of complications, eventually leading to renal failure. At the same time, the elimination of intravesical hypertension is not an easy task, since damage to the spinal cord pathways is chronic and requires long-term therapy; combination of a number of drugs using the liver enzyme system, requires the use of the safest and most reliable pharmacological options. The use of M-anticholinergics, which do not affect the central nervous system, while maintaining effectiveness for a long time, is particularly relevant in this regard.

Methods. Of the group of patients who were followed-up with a diagnosis of spinal disease, seven underwent invasive studies (liquid retrograde cystometry). The multichannel analytical urodynamic system «ALFA» and the «UROVEST» software version 8.1 were used for urodynamic examination. To correct DHA, a peripherally acting M-anticholinergic trospium chloride (Spasmex) was prescribed at a dose of 30 mg twice a day. Repeated urodynamic examination was scheduled after 4–9 weeks.

Results. The most interesting result of the study was a decrease in DHA under the influence of Spasmex. When recalculating the increase in «dynamic» tone with detrusor contraction, this parameter decreased by 22%, while the «static» tone of the bladder wall decreased from 26.8 mm H2O at the end of the study to 6.4 mm H2O. The pressure at the end of the filling stage also decreased.

Conclusion. The drug Spasmex (trospium chloride), having antispasmodic and M-anticholinergic effects, is an effective tool to reduce the intravesical hypertension level in patients with spinal disease. Long-term administration of the drug eliminates the risk of renal complications. The drug has the property of good compatibility in the management of patients with injuries of the spine and spinal cord, which allows it to be prescribed together with α-blockers, vitamins and nootropics.

Pharmateca. 2023;30(4/5):79-83
pages 79-83 views

Retrospective analysis of the frequency of recurrent endometrial polyps in women in the reproductive period using hospital-replacing technologies

Vinogradova O.P., Petrova M.V., Shvetsova O.B., Kovylina M.V., Kalmakova E.N., Barakova-Bezuglaya M.E.

Abstract

Background. According to statistics, the frequency of recurrence of endometrial polyps (EP) is 25.9–78%. Despite the knowledge of the pathology, the diagnosis of RP is confirmed histologically only in 50–82% of cases [5, 8, 14]. One of the urgent problems of modern gynecology is to improve the efficiency of diagnosing endometrial pathology on an outpatient basis, clarifying the causes and preventing relapses.

Objective. Identification of the frequency of EP recurrence in patients of reproductive age, evaluation of the existing diagnostic methods and identification of possible causes of EP recurrence based on a retrospective analysis.

Methods. A retrospective analysis of the case histories of 1356 patients (mean age 47.8±0.6 years) with a diagnosis of EP over a three-year period, followed by an analysis of the case histories of 246 women of reproductive age (mean age 36.6±0.8) and 52 patients of reproductive age with EP recurrence was carried out.

Results. According to the data obtained from all observed patients with EP, 18.1% were women of reproductive age. At the same time, the frequency of EP recurrence in the examined women of reproductive age was 21.2% (52 patients). In 14 (26.9%) patients, a relapse occurred on the background of hormonal therapy. Also, 25% of the examined patients had a combination of relapse with a hyperplastic process of the genitals: adenomyosis, uterine myoma, endocervical polyp. At the same time, extragenital pathology, most often pathology of the thyroid gland, was revealed in all examined women.

Conclusion. In the diagnosis of EP, office hysteroscopy and ultrasound provide a high percentage of concurrence of diagnoses, in addition, office hysteroscopy is effective in diagnosing concomitant intrauterine pathology. In the presence of ultrasound diagnostics and office hysteroscopy in the diagnosis of pathology of the uterine cavity, priority should be given to office hysteroscopy due to the accuracy of diagnosis and the possibility of obtaining a biopsy for histological confirmation of the diagnosis. EP recurrence in women of reproductive age was noted in 21.2% of cases. In every fourth patient, a relapse occurred against the background of combined hyperplastic processes of the genitals, as well as against the background of hormonal therapy or hormonal contraception.

Pharmateca. 2023;30(4/5):84-89
pages 84-89 views

Arterial hypertension in pregnant women: «comorbidity» or a risk factor for postoperative infectious complications?

Korobkov N.A., Bakulina N.V., Maximov M.V.

Abstract

Background. The risk of infectious complications after caesarean section in patients with arterial hypertension has not been studied enough.

Objective. to do research on the causal link between hypertensive disorders during pregnancy and the development of endometritis after caesarean section; to determine the prognostic value of arterial hypertension as an independent predictor of the development of postoperative infectious and inflammatory complications.

Methods. A retrospective study analysis of case histories and data from medical source records of 406 puerperas with endometritis after caesarean section and 242 puerperas with an uncomplicated postoperative period is completed.

Results. The frequency of hypertensive disorders during pregnancy is quite evident. The level of postpartum infectious morbidity wasn’t higher in puerperas with pregnancy-induced arterial hypertension (preeclampsia, gestational hypertension). As known, preeclampsia can develop faster in women having antenatal infection in past medical history, however, the inverse assumption about a higher number of postpartum infectious complication in preeclampsia has proved to be incorrect.

Conclusion. Chronic arterial hypertension complicates the course of pregnancy 10.8 times more frequently in puerperas with endometritis after caesarean section (8.6% vs. 0,8%; χ2=17,11; p<0,001). It makes possible to refer this hypertension to significant predictors of developing of infectious and inflammatory complications. It requires a more careful monitoring of the pregnant woman and the puerperal to prevent this type of complications. It can also serve as the basis for the subsequent construction of a prognostic risk model.

Pharmateca. 2023;30(4/5):90-95
pages 90-95 views

The effectiveness of intimate biorevitalization in the treatment of symptoms of vulvovaginal atrophy

Saidova A.S., Dudkina A.R., Teterina T.A., Apolikhina I.A.

Abstract

Background. The problems of women’s reproductive aging and the need to maintain and improve the quality of life and health of women during the period of age-related changes are an urgent task of modern medicine, especially in the light of existing demographic trends. Genitourinary menopausal syndrome (GUMS) is a symptom complex that occurs in women against the background of a deficiency of estrogens and other sex steroids, including physiological and anatomical changes in the vagina, urethra, bladder, vulva and perineum.

Objective. Evaluation of the effectiveness of vulva biorevitalization with preparations based on hyaluronic acid (HA) in combination with hardware methods for the relief of local symptoms of GUMS and lichen sclerosus (LS).

Methods. The study included 40 patients: 20 with GUMS (group 1) and 20 with LS (group 2). The follow-up period was up to 6 months. Patients aged 24–65 years were included, the median age of patients in both groups was 42 years. Injections with MesoHydral or Hydro Line Extra (in both groups) or Nucleospire DNA-RNA 2% (only in the LS group) were administered. All patients tolerated the procedures well, there were no side effects, and the patients were satisfied with the treatment.

Conclusion. Thus, preparations of this type can be recommended not only for practical use, but also for further, possibly more detailed and broad study of the spectrum of their capabilities.

Pharmateca. 2023;30(4/5):96-103
pages 96-103 views

Regional experience with universal screening for total cholesterol in children

Sadykova D.I., Kamalova A.A., Rakhmaeva R.F., Makarova T.P., Melnikova Y.S., Galimova L.F., Slastnikova E.S., Mustafaeva A.A., Petrova M.A., Garipova A.A., Kalistratova Y.A., Shtyrkova A.V., Sеnеk S.А.

Abstract

Background. The prevalence of risk factors for cardiovascular disease (CVD) is rapidly increasing. The world has accumulated clinical experience in screening for the detection of lipid metabolism disorders, but such studies have not been conducted in children in Russia.

Objective. Determination of the risk groups for the development of CVD among children based on the assessment of the hereditary factor, the level of physical development and blood total cholesterol (TC).

Methods. A cross-sectional study was conducted in 542 children aged 10 years (49% of boys and 51% of girls), and included signing of informed consent, questionnaires, study of child’s record, anthropometry with WHO AnthroPlus assessment, blood pressure measurement, determination of TC level by MultiCare-in express method (Italy).

Results. According to the survey data, risk factors included the presence in second-line relatives: myocardial infarction – in 15% of children, stroke – in 19%, arterial hypertension – in 40%, excess body weight – in 24%, diabetes mellitus – in 22%, vascular surgery heart and head - in 9%, smoking – in 63%. Nutritional disorders were revealed in 48% of children: underweight in 21% of children, overweight in 17%, obesity in 10%. In 35% of children, an increased TC level was determined. A high TC level was detected both in children with underweight and in children with overweight and obesity. In 7% of children (n=38), systolic blood pressure was above the 90% percentile.

Conclusion. Risk groups for the development of CVD were identified, including children with an elevated TC level, systolic blood pressure above the 90% percentile, and nutritional status disorders. A high TC level in children with normal physical development dictates the need for a more detailed assessment of the nutritional status with the determination of the component composition of the body. Children with a capillary TC level of more than 5.2 mmol/L should be examined for TC in venous blood; and a differential diagnosis of primary and secondary genesis of dyslipidemia should be made.

Pharmateca. 2023;30(4/5):104-108
pages 104-108 views

Current approaches to the treatment of functional constipation in children

Ermolenko K.D., Kirilenko L.A., Dolgikh V.V.

Abstract

Background. Among all functional gastrointestinal disorder, the most common nosological form is functional constipation (FC). In Western countries, it is estimated to be diagnosed in 2–27% of the population. The expansion of ideas about the mechanisms of the formation of FC contributes to the expansion of the possibilities of treating this condition.

Objective. Evaluation of the effectiveness of various treatment regimens for FC in children.

Methods. The study included 106 patients aged 4 to 17 years, 51 (48.1%) were boys and 55 (51 .9%) girls, who underwent outpatient treatment due to FC at the Consultative and Diagnostic Center of the Children’s Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency. Rome IV criteria were used for the diagnosis of FC. Drug treatment of FC was carried out in three groups formed in accordance with the treatment regimen: group 1 – lactulose (n=39), group 2 – functional food product (FPP) “multi-grain protein-spelled” bread (n=33), group 3 – lactulose+FPP functional “multi-grain protein-spelled” bread (n=34). Intestinal microbiocenosis in children was assessed at the beginning of treatment and on the 21st day by examining fecal samples by real-time PCR, which was performed at the Department of Molecular Microbiology, Institute of Experimental Medicine.

Results. Complete pain relief after the course of treatment was achieved in 64 children (60.4%). Depending on the chosen drug regimen, there were significant differences in the frequency of complete long-term relief of FC symptoms: in group 1 – in 21 (53.8%), in group 2 – in 19 (57.6%), in group 3 – in 24 (70, 6%). Decrease in the Lactobacillus spp. and Bifidobacterium spp. level was most typical. This indicator was lower than the reference values by 2 lg CFU/g in 22 children from group 3 (64.7.7%) and 24 children from group 2 (72.7%). It should also be noted that the use of functional bread “protein spelled many grains” contributed to the restoration of normal levels of these parameters.

Conclusion. Combination therapy of FC using functional bread “protein spelled many grains” in combination with laxatives increases the effectiveness of treatment, providing a significantly more effective restoration of microbiocenosis parameters and a reduction in the duration of clinical symptoms. The use of functional bread “protein spelled many grains” as monotherapy also had an effect on the symptoms of the disease, contributing to the normalization of the frequency of bowel movements and the reduction of symptoms associated with stool retention.

Pharmateca. 2023;30(4/5):109-114
pages 109-114 views

Efficacy of pentahydroxyethylnaphthoquinone for the treatment and prevention of retinopathy of prematurity

Feoktistova Y.V., Poddubniy E.A., Tyrtyshnikova A.V., Eliseeva E.V., Feoktistova E.D., Shulgina N.A.

Abstract

Background. Retinopathy of prematurity (RP) remains one of the causes of bilateral visual impairment in children. The main cause of RP is not only an imbalance of factors regulating angiogenesis, but also oxidative stress.

Objective. Meta-analysis of studies of the pentahydroxyethylnaphthoquinone, which was developed, patented and has a full production cycle in the Russian Federation; evaluation of the effectiveness of its use in premature newborns to prevent the development and progression of retinopathy.

Methods. The effectiveness of pentahydroxyethylnaphthoquinone in premature newborns to prevent the development and progression of retinopathy was evaluated.

Results. A pilot meta-analysis on the use of pentahydroxyethylnaphthoquinone indicates its benefits in preventing the development and progression of retinopathy. The results depend on the methodology and methods of the study, and therefore should be taken with caution. At the same time, the findings correlate with the positive experience of using this drug in the Russian Federation.

Conclusion. The minimum number of studies included in the meta-analysis allows for indicative results. With a large number of studies in different groups of patients, it is possible that different results will be obtained.

Pharmateca. 2023;30(4/5):115-120
pages 115-120 views

Pharmacogenetic factors of haloperidol’s safety in adolescents experiencing acute psychotic episodes

Ivashchenko D.V., Kravchenko A.Y., Khoang S.Z., Buromskaya N.I., Shimanov P.V., Deitch R.V., Nastovich M.I., Akmalova K.A., Kachanova A.A., Savchenko L.M., Shevchenko Y.S., Sychev D.A.

Abstract

Background. Pharmacogenetic testing is an effective method of predicting the safety of pharmacotherapy. Some antipsychotics can now be prescribed based on genotyping results - for example, haloperidol. The pharmacogenetics of haloperidol safety in adolescents with an acute psychotic episode are poorly understood at this time.

Objective. To identify pharmacogenetic predictors of adverse reactions to haloperidol in adolescents with an acute psychotic episode.

Methods. A prospective observational study included 56 adolescents diagnosed with acute polymorphic psychotic disorder. Patients were followed up for 14 days. All patients received haloperidol as their primary pharmacotherapy. Safety of psychopharmacotherapy was assessed using UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7776746), CYP2D6*4,*9 gene polymorphisms,*10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), COMT rs4680 (G>A - Val158Met), DRD3 rs6280 (C>T), DRD3 rs324026 (C>T), HTR2A rs6313 (T102C), ZNF804A rs1344706 (G>T), ANKS1B rs7968606 (C>T) were determined by real-time polymerase chain reaction (PCR). Results. Carriage of the COMT rs4680 polymorphism (Met allele) was associated with a lower severity of adverse psychiatric reactions. The presence of the HTR2A rs6313 and ZNF804A rs1344706 polymorphisms was significantly associated with a higher UKU SERS scale score. Carriers of the HTR2A rs6313 polymorphism variant (TC+CC genotypes) complained more frequently about the development of tremor (37.2 vs. 0%, p=0.009). Carriage of ABCB1 1236C>T and 2677G>T/A was more frequently associated with the presence of orthostatic vertigo (35 vs. 6.3%, p=0.028, due to nonequilibrium linkage, the data were the same for both polymorphic variants). The incidence of orthostatic vertigo was significantly higher in carriers of the ZNF804A rs1344706 polymorphism (37.5 vs. 12.5%; p=0.037). Carriers of the DRD3 rs6280 and rs324026 polymorphisms were less likely to develop «increased dream intensity.»

Conclusion. An increased risk of adverse reactions was observed in carriers of HTR2A rs6313 polymorphisms (TC+CC genotypes), ABCB1 1236C>T and 2677G>T/A, ZNF804A rs1344706. Carriage of COMT rs4680 (Met allele), DRD3 rs6280 and rs324026 was found to be associated with a lower severity of adverse reactions compared to «wild-type» genotypes.

Pharmateca. 2023;30(4/5):121-126
pages 121-126 views

Problem

Pharmacotherapeutic aspects of gestational diabetes mellitus against the background of impaired maternal immunity

Kazimova A.U., Polukhova S.M.

Abstract

This article discusses the immune status of the mother in gestational diabetes mellitus (GDM). Normal pregnancy is characterized by a controlled state of the immune system at the early stages of pregnancy. Various immunological mediators adapt to the state of pregnancy, all of which affect maternal and fetal health. GDM, defined as impaired glucose tolerance of any degree during pregnancy, is a serious obstetric complication affecting approximately 5–10% of pregnant women worldwide. Hyperglycemia causes immune dysfunction by negatively affecting neutrophil chemotaxis, macrophage function, and phagocytic responses, making diabetic patients more susceptible to infections and associated comorbidities. The state of pregnancy along with immunological changes, imbalances of innate and adaptive cellular responses present additional health risks. Insulin plays an indispensable role in the treatment of hyperglycemia that occurs in various conditions, including in type I and type II diabetes; insulin has an anti-apoptotic effect and reduces the expression of pro-inflammatory cytokines in human endotoxemic macrophages. Metformin or sulfonylurea derivatives may also be used for the treatment of GDM. Metformin suppresses immune responses mainly through its direct effect on the cellular functions of various types of immune cells. Glyburide enhances the anti-inflammatory response and synergizes with retinoic acid. A better understanding of development if immune dysfunctions during hyperglycemia could lead to new treatments and prevention for infectious diseases and DM2 comorbidities, thereby improving infectious disease outcomes in DM2 patients. These results require further study of the role of drugs such as insulin, metformin, and glyburide in the immunoregulation of the pathophysiology of GDM.

Pharmateca. 2023;30(4/5):127-132
pages 127-132 views

Pharmacological properties of drugs

The role of systemic enzyme therapy with phlogenzym in the prevention of postoperative complications in gynecological practice

Apolikhina I.A.

Abstract

Surgical treatment in gynecological practice is characterized by a relatively high incidence of postoperative complications, including pain, inflammation, infections, adhesions, etc. Systemic oral enzyme therapy can contribute to the prevention of complications and their effective relief. The drug Flogenzym has the necessary anti-inflammatory, analgesic and antiplatelet effects due to the complex action of its components, successfully prevents and reduces the intensity of possible negative consequences of surgical treatment.

Pharmateca. 2023;30(4/5):133-137
pages 133-137 views

Improving the efficiency and safety of iron deficiency treatment using micellar microencapsulation of iron (SUNACTIVE® Fe)

Shikh E.V., Emelyanova L.V.

Abstract

To date, Russia continues to rank among countries with significant public health problems in terms of the prevalence of iron deficiency. The main strategy for the prevention of iron deficiency in reproductive age is the additional intake of dietary supplements. However, according to statistics, up to 40% of patients stop taking iron supplements early due to side effects, which dictates the search for new ways to improve adherence to treatment. To this end, two directions are considered: changing the dosing regimen and the use of iron compounds produced using modern technologies that provide increased safety without compromising bioavailability and effectiveness. Iron pyrophosphate is a trivalent compound with very good tolerability but low bioavailability due to the low water solubility. The special patented SUNACTIVE® nanotechnology provies maximum micronization of iron pyrophosphate to 0.3 microns, followed by micellization as part of lipophilic nanoparticles, which are most similar in structure to chylomicrons. The absorption of such a highly micronized form of iron pyrophosphate is comparable to that of ferrous sulfate, which is a reference for assessing the bioavailability of various iron salts. Lipophilic micelles additionally protect iron from the acidic environment of the stomach and create a natural transport system that provides a direct route for Fe3+ transport through M cells. This route of absorption helps the rapid entry of iron through the enterocytes into the lymph and then into the liver for incorporation into ferritin and transferrin. Part of the micelles release iron under the action of digestive enzymes in the duodenum and the beginning of the small intestine. Ascorbic acid promotes the transition of Fe3+ to Fe2+, which provides an additional pathway for iron absorption through ion transport with the participation of the divalent metal transporter DMT-1. BADS Bonoferlat* is a combination of micronized iron pyrophosphate produced in Italy using the patented SunActive® Fe micellar microencapsulation technology and L-ascorbic acid. One capsule of Bonoferlat contains 30 mg of iron and 110 mg of ascorbic acid, which provides an effective molar ratio between them for adequate restoration of valence from Fe3+ to Fe2+. The iron in Bonoferlat is well tolerated, does not cause side effects from the gastrointestinal tract and does not interact with dairy products, tea, coffee and other foods, so it can be taken at any convenient time without loss of effectiveness. In the context of the growing prevalence of iron deficiency states, it is advisable to use Bonoferlat in strategies for the prevention of iron deficiency with an increased need for iron, to compensate for iron deficiency that occur due to the insufficient intake of heme iron with food as a result of diets or dietary habits, in violation of iron absorption, as well as to compensate for the deficiency iron in the complex therapy of iron deficiency anemia and sideropenia of various etiologies.

Pharmateca. 2023;30(4/5):138-144
pages 138-144 views

Effective methods of treatment of “thin” endometrium in patients of reproductive age

Efendieva Z.N., Makovskaya D.S., Apolikhina I.A.

Abstract

This article provides an analysis of the data presented in the world literature regarding the role of the endometrium in terms of reproductive failures, as well as modern methods of treating infertility caused by uterine factor. The review includes the results of studies and meta-analyses published in PubMed journals on this topic. The combination of many factors that affect the effectiveness of the interaction between the embryo and endometrial tissue makes it difficult to identify the true causes of reproductive failure in patients with uterine factor infertility. To date, the main methods of treating infertility associated with thinning of the endometrium are aimed at stimulating its growth and improving the blood supply to the uterus. A relatively new, but very promising direction in modern regenerative and reproductive medicine is the use of autologous platelet-rich plasma (Platelet-Rich Plasma – PRP) in patients with reproductive failures.

Pharmateca. 2023;30(4/5):145-149
pages 145-149 views

Symptoms of menopausal disorders during perimenopause (review article)

Ilyina I.Y.

Abstract

The menopausal transition is an important period in a woman’s life, which is characterized not only by the irregularity of the menstrual cycle, but also by vasomotor manifestations, sleep disturbances, mood lability, depressive disorders, and initial manifestations of urogenital disorders. All of the above manifestations increase as the estrogen deficiency progresses. The use of menopausal hormone therapy (MHT) is the main pathogenetically substantiated method of treating manifestations of estrogen deficiency. However, when prescribing MHT, it is important to take into account all contraindications and the risks of developing complications against its background. Therefore, there is a need to select alternative methods for eliminating the symptoms of menopausal syndrome. In this case, metabolic therapy may be recommended as an additional method of treatment. In the presence of manifestations of an overactive bladder, the first-line drugs are M-cholinolytics. When choosing a drug from this group, it is important to take into account the features of its pharmacological action, the presence of concomitant pathology in the patient, the possibility of interaction with other drugs, the risks of side effects. In our opinion, trospium chloride meets all the requirements and can be recommended.

Pharmateca. 2023;30(4/5):145-149
pages 145-149 views

Polycystic ovary syndrome phenotypes

Pustotina O.A.

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with up to 70% of cases remaining undiagnosed as a result of significant clinical heterogeneity. This review describes in detail the diagnostic criteria for PCOS, analyzes the existing phenotypes of the disease, and also describes the etiopathogenetic significance of insulin resistance (IR) in the development of hyperandrogenism and reproductive disorders. For the choice of treatment tactics, the importance not only of accurate diagnosis of PCOS, but also of determining the clinical phenotype of the disease with a detailed analysis of the morphological structure of the ovaries and an additional study of metabolic parameters, such as body weight and IR index, is emphasized. A differentiated approach to the prescription of insulin sensitizers for various PCOS phenotypes has been substantiated.

Pharmateca. 2023;30(4/5):156-163
pages 156-163 views

LECTURE

A new format for conducting classes in antenatal clinics with pregnant and lactating women in the modern world realities

Gmoshinskaya M.V., Aleshina I.V.

Abstract

The article is devoted to the formation of the dominant of motherhood and breastfeeding in women. A course of classes and lectures has been developed, including issues of nutrition during pregnancy, breastfeeding, care, nutrition of a child in the first year of life. The effectiveness of the developed course was evaluated.

Pharmateca. 2023;30(4/5):164-168
pages 164-168 views

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