Vol 75, No 3 (2020)


Papillomavirus infection and reproduction

Krasnopolsky V.I., Zarochentseva N.V., Krasnopolskaya K.V., Bashankaeva Y.N., Kuzmicheva V.S.


The purpose of the review — a synthesis of research data on the role of human papillomavirus infection in the reproductive health of women and men.

Key Points. Human papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. According to the World Health Organization, HPV is the main cause of the development of HPV-associated diseases among both women and men. Viruses are subdivided into HPV with low carcinogenic risk, which cause benign warts, and HPV with high carcinogenic risk, which cause cancer. Different types of human papillomaviruses depending on their characteristic tropism, are divided into skin and mucous types. Viral infection in men leads to a decrease in the quality of sperm (for example, asthenozoospermia) due to apoptosis in sperm cells and due to the development of antisperm immunity. A negative viral effect on the fertility of women is manifested in an increase in the frequency of spontaneous miscarriages and a premature rupture of the amniotic membranes during pregnancy. There is evidence that HPV decreases the number of trophoblastic cells and abnormal trophoblastic-endometrial adhesion is also observed. In trophoblastic cells transfected with high-risk HPV, the level of apoptosis increases. HPV vaccination is safe, and the results show not only protection against HPV-associated diseases in women and men, but also a reduction of gestational complications, reduced preterm birth rates and the protection of newborns from infection.

Annals of the Russian academy of medical sciences. 2020;75(3):189-195
pages 189-195 views


Free radical reactions in socially significant infectious diseases: HIV infection, hepatitis, tuberculosis

Darenskaya M.A., Kolesnikova L.I., Kolesnikov S.I.


The analysis of current literature data on the study of the features of the course of free-radical reactions, as well as the state of the antioxidant defense system at socially significant infectious diseases — HIV infection, hepatitis, tuberculosis was carried out. The role of this kind of reaction in the genesis and progression of socially significant infections a long time has been studied. Foreign studies of recent years have been focused on the identification of specific markers of oxidative and carbonyl stress, which make it possible to identify the redox imbalance of the cell under conditions of infection and target affect it to modulate the activity of the main transcription factors of viral proteins and the bacteria pathogenicity. Numerous sources indicate the involvement of active oxygen metabolites in a wide range of events in infected cells and tissues, including neoplastic transformation processes. These biochemical markers can be used as additional criteria for monitoring the progression of infection. At the same time, noticeable gaps in this area there are that may become the goal of future research. The issues of changing free radical reactions depending on gender, age, place of residence of patients remain practically unstudied. There is little data about intensity of oxidative stress in patients of reproductive age with HIV, hepatitis B and C, and pulmonary tuberculosis, as well as the relationship of antioxidant deficiency with reproductive disorders in conditions of infection. These data could serve as the basis for the development of pathogenetically substantiated methods for the correction of socially significant infectious diseases. Modulation of the production of reactive oxygen metabolites and oxidative stress is a potentially new pharmacological approach to reduce the effects of viral and bacterial exposure.

Annals of the Russian academy of medical sciences. 2020;75(3):196-203
pages 196-203 views


Hyperstimulation of the immune system as a cause of autoimmune diseases

Ryabkova V.A., Churilov L.P., Shoenfeld Y.


The pathogenesis of autoimmune diseases is very complex and multi-factorial. The concept of “Mosaics of Autoimmunity” was introduced to the scientific community 30 years ago by Y. Shoenfeld and D.A. Isenberg, and since then new tiles to the puzzle are continuously added. This concept specifies general pathological ideas about the multifactorial threshold model for polygenic inheritance with a threshold effect by the action of a number of external causal factors as applied to the field of autoimmunology. Among the external factors that can excessively stimulate the immune system, contributing to the development of autoimmune reactions, researchers are particularly interested in chemical substances, which are widely used in pharmacology and medicine. In this review we highlight the autoimmune dynamics — i.e. a multistep pathogenesis of autoimmune diseases and the subsequent development of lymphoma in some cases. In this context several issues are addressed — namely, genetic basis of autoimmunity; environmental immunostimulatory risk factors; gene/environmental interaction; pre-clinical autoimmunity with the presence of autoantibodies; and the mechanisms, underlying lymphomagenesis in autoimmune pathology. We believe that understanding the common model of the pathogenesis of autoimmune diseases is the first step to their successful management.

Annals of the Russian academy of medical sciences. 2020;75(3):204-213
pages 204-213 views


COVID-19, septic shock and syndrome of disseminated intravascular coagulation syndrome. Part 2

Bitsadze V.O., Khizroeva J.K., Makatsariya A.D., Slukhanchuk E.V., Tretyakova M.V., Rizzo G., Gris J., Elalamy I., Serov V.N., Shkoda A.S., Samburova N.V.


The article discusses the issues of hemostatic system disorders in patients with COVID-19. Strengthening the coagulopathy characteristic of DIC-syndrome, is a key sign of deterioration and an unfavorable prognosis in COVID-19 patients. Data obtained by Chinese colleagues demonstrates that a significantly increased level of D-dimer is one of the predictors of death. The article also highlights the preliminary recommendations of the International society of Thrombosis and Hemostasis (ISTH, 2020) to identify markers such as D-dimer, prothrombin time and platelet count as significant predictive markers in severe COVID-19 patients. The necessity of anticoagulant therapy in hospitalized patients is justified. The article discusses the features of sepsis in pregnant women. Data from a meta-analysis of 19 studies evaluating pregnancy complications and outcomes in patients with various coronavirus infections are presented. Despite the complicated course of pregnancy, there were no cases of vertical transmission of viral infection. In the pathogenesis of severe COVID-19 complications with the formation of severe acute respiratory distress syndrome, multi-organ dysfunction, super inflammation and cytokine storm play a leading role. In connection with viral sepsis, the article discusses the role of hemophagocytic lymphohistiocytosis as a hyperinflammatory syndrome characterized by fulminant and fatal hypercytokinemia with multiple organ failure, the role of hyperferritinemia in predicting the outcomes of severe sepsis. Groups of patients at high risk of death are discussed, as well as the need for anticoagulant and anti-cytokine therapy in patients with COVID-19.

Annals of the Russian academy of medical sciences. 2020;75(3):214-225
pages 214-225 views


C-fos, ERK1/2, MAP2, NOTCH1 Proteins Expression Patterns in Human Cerebral Cortex Neurons after Ischemic Stroke

Sergeeva S.P., Lyundup A.V., Beregovykh V.V., Litvitskiy P.F., Savin A.A., Gorbacheva L.R., Kiseleva E.V., Breslavich I.D., Kutsenko K.I., Shishkina L.V.


Background. The search for protein (these include c-fos, ERK1/2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task.

Aims — to reveal c-fos, ERK1/2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS.

Materials and methods. We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 — the zone adjacent to the necrotic tissue focus; 2 — zone remote from the previous one by 4–7 cm; 3 — zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1/2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method.

Results. Moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1/2 and MAP2 positive neurons compared to the control only in samples of zone 1.

 Conclusions. With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.

Annals of the Russian academy of medical sciences. 2020;75(3):226-233
pages 226-233 views


Organizational aspects of improving primary diagnosticsmalignant neoplasms of visual localizations in the rural municipal area

Vazhenin A.V., Voroshina N.V., Domozhirova A.S.


Background. The proportion of malignant neoplasms detected at the III–IV stages of the disease in Chelyabinsk region is large and 43.9%. Breast cancer in 2018 was detected at stages III–IV at 24% and cervical cancer at 51.14%. Despite the fact that malignant neoplasms of vulva and vagina are diagnosed annually in isolated cases, the level of neglect reaches 66.7 and 100% respectively, which makes it necessary to develop organizational measures.

Aims — to increase the level of detection of visual localities OF female reproductive system organs in the early stages with the involvement of oncologists of regional clinics in the primary diagnosis.

Materials and methods. Patients with malignant neoplasms of the reproductive system of visual localizations, first identified in the examining cabinet of the polyclinic of the central district hospital, geographically located and functionally subordinate oncologist of the rural municipal district. Comparative assessment of early detection of tumors in an area with high breast cancer and cervical cancer and results following the introduction of a new organizational structure.

Results. Patients with malignant neoplasms of the reproductive system of visual localizations, first identified in the examining cabinet of the polyclinic of the central district hospital, geographically located and functionally subordinate oncologist of the rural municipal district. Comparative assessment of early detection of tumors in an area with high breast cancer and cervical cancer and results following the introduction of a new organizational structure.

Conclusions. The involvement of oncologist of territorial polyclinics to participate in preventive examinations, which were previously within the competence of the medical assistant of the “Examining Cabinet”, during the first year of work increased detection and reduced the incidence of breast and cervical cancer by 8.3 and 3.7% respectively. The creation of the “Breast Pathology Center” in the regional oncology center, at the third level of specialized medical care on the profile of oncology, allowed to reduce the frequency of malignancy of benign and pre-cancer breast diseases.

Annals of the Russian academy of medical sciences. 2020;75(3):234-239
pages 234-239 views


Osteosarcopenia: pathogenesis, diagnosis and therapeutic approaches

Grebennikova T.A., Tsoriev T.T., Vorobeva J.R., Belaya Z.E.


Osteosarcopenia was identified as a separate syndrome in 2009, and is defined as a combination of sarcopenia and osteopenia/osteoporosis. Osteosarcopenia develops mainly in old age, leads to a decrease in quality of life, an increased risk of falls and low-traumatic fractures. Patients with osteosarcopenia have worse indicators of physical functions, compared with people suffering from only one of the components of the syndrome. An important role in the osteosarcopenia prevention is played by the lifestyle of patients, Adherence to diet with the consumption of adequate amount of protein, physical activity and preventive prescription of calcium and vitamin D are important for osteosarcopenia prevention. The article summarizes data on the prevalence, pathogenesis and risk factors of osteosarcopenia, provides diagnostic criteria for the disease and discusses therapeutic approaches.

Annals of the Russian academy of medical sciences. 2020;75(3):240-249
pages 240-249 views


Endocrine ophthalmopathy: pharmacogenetic markers of efficiency of glucocorticoid therapy

Toropova O.S., Brovkina A.F., Sychev D.A.


The pathological process of endocrine ophthalmopathy is based on damage to the soft tissues of the orbit against the background of impaired thyroid function and even its euthyroid state. The pathogenetic mechanisms of the development of clinical symptoms of endocrine ophthalmopathy (EOP) are based on morphological changes in extraocular muscles (EOM) and orbital tissue: cellular tissue infiltration by representatives of the immune system (T- and B-lymphocytes, macrophages, mast and plasma cells), with the production of pro-inflammatory cytokines, fibroblasts and glycosaminoglycans, contributing to an increase in the contents of the orbit in volume with the development of exophthalmos and tissue fibrosis at the end of the inflammatory process. Glucocorticoids are the “gold standard” for the pathogenetic treatment of patients with clinical forms of endocrine ophthalmopathy: edematous exophthalmos and endocrine myopathy. The properties of drugs of this group are such that they can be used to suppress all stages of inflammation in the orbital tissues, preventing the progression of the disease. Despite the many years of experience in applying various glucocorticoid therapy techniques, to date there are no uniform criteria for the effectiveness of this treatment in patients with endocrine ophthalmopathy. The article presents the features of glucocorticoid therapy of endocrine ophthalmopathy, as well as literature data, on the basis of which attempts have been made to explain the causes of glucocorticoid resistance taking into account the pharmacogenetic profile.

Annals of the Russian academy of medical sciences. 2020;75(3):250-255
pages 250-255 views


Clinical trials — the personal perspective of the research physician?

Egorova M.Y., Shuvalova I.A., Zvonareva O.I., Pimenov I.D., Kobyakova O.S., Deev I.A., Kulikov E.S.


Background. The organization of clinical trials (CTs) requires the participation and coordination of healthcare providers, patients, public and private parties. Obstacles to the participation of any of these groups pose a risk of lowering the potential for the implementation of CTs. Researchers are a key human resource in conducting of CT. Their motivation for participation can have a significant impact on the recruitment and retention of patients, on the quality of the data collected, which determines the overall outcome of the study.

Aims — to assess the factors affecting the inclusion of Russian physicians-researchers in CT, and to determine their role in relations with patients-participants.

Materials and methods. The study was organized as a part of the Russian multicenter face-to-face study. A survey was conducted of researchers from 10 cities of Russia (2017–2018). The participation in the survey for doctors was anonymous and voluntary.

Results. The study involved 78 respondents. Most research doctors highly value the importance of research for science (4,84 ± 0,39), society (4,67 ± 0,46) and slightly lower for participating patients (4,44 ± 0,61). The expectations of medical researchers are related to improving their financial situation and attaining new experience (n = 14; 18,18%). However, the opportunity to work with new technologies of treatment and diagnosis (n = 41; 52,56%) acted as a motivating factor. According to the questionnaire, the vast majority of research doctors (n = 29; 37,18%) believe that the main reason for patients to participate in CT is to receive quality and free medical care. The most significant obstacle to the inclusion of participants in CT was the side effects of the study drug (n = 38; 48,71%).

Conclusions. The potential of clinical researchers in Russia is very high. The patient-participant acts for the research doctor as the subject of the study, and not the object, so the well-being of the patient is not indifferent to the doctor. However, the features of the functioning of our health care system form the motivation of doctors-researchers (additional earnings, professional self-development) and the way they perceive the motivation of patients (CT as an opportunity to receive quality medical care).

Annals of the Russian academy of medical sciences. 2020;75(3):256-263
pages 256-263 views

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