UDC 616.24-002.5-036.22-085.28.015.8-085.37-039.71-053.2

Aim – to study the feasibility of using the natural immunomodulator BIVEL (BI-V) as a non-specific immunoprevention of tuberculosis (TB) among contact children from focies of multidrug-resistant tuberculosis infection (FsMDR-TBI) on the basis of clinical and immunological studies.
Materials and methods. The object of study: 120 contacted from FsMDR-TBI (75 children and 45 adolescents). The Group 1 – 95 children/adolescents who did not receive BI-V and the Group 2 – 25 patients who received BI-V. The state of phagocytic reactivity of immunity; cellular and humoral immunity; interleukins and specific immunity were determined. Statistical analysis of the obtained results was performed based on a software package Excel.
Results. In infected children/adolescents with FsMDR-TBI, insignificant functional disorders of the cellular response were revealed (decrease by 1.3 times IRI CD3+CD4+/CD3+CD8+), a shift in the balance in the regulatory system towards pro-inflammatory cytokines (increase by 2.0 times TNF-α/IL-10). The existing deviations in the regulatory and cellular response systems disappeared after the completion of the autumn-spring BI-V course. Preventive administration of immunomodulator BI-V to infected children/adolescents with FsMDR-TBI reduced the frequency of acute respiratory viral infections and exacerbations of bronchopulmonary diseases by 2.0 times, the development of latent tuberculosis infection into an active process by 2.6 times. Among children of the Group 2 – 8% of people fell ill with various forms of primary pulmonary TB, among children of the Group 1 – 22.1%. In both groups, the maximum level of TB occurred in the first two years of observation.
Conclusions. The introduction of the algorithm of preventive measures with appointment of BI-V confirmed feasibility of using this immunomodulator for contact children/adolescents with FsMDR-TBI.
The study was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethical 
Committee of the participating institution. The informed consent of patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: immunoprevention, contact children and adolescents, focies of multidrug-resistant tuberculosis.

УДК: 616.24-002.5:615.015.8]-085.281-078.73-036.8-053.2/6

BACKGROUND. The feasibility of combining antimycobacterial therapy (AMBT) with bedaquiline (Bdq) and delamanid 
(Dlm) with non-specific immunomodulator BI-V in children and adolescents with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/Rif-TBP) needs to be studied.
OBJECTIVE. To find out the effectiveness of the use of complex AMBT with Bdq and Dlm with non-specific immunomodulator BI-V in children and adolescents with MDR/Rif-TBP.
MATERIALS AND METHODS. Children and adolescents with MDR/Rif-TBP at the initial stage of AMBT were given BI-V 
(BIVEL, Slovenia) as a non-specific immunomodulator. The patients were divided into two groups: 1st – 20 patients who received Bdq + Dlm + levofloxacin (Lfx) + linezolid (Lzd) + clofazimine (Cfz); 2nd ‒ 28 patients whose complex treatment included BI-V (Вdq + Dlm + Lfx + Lzd + Cfz + BI-V). BI-V was prescribed from the age of 3 years at 5 ml suspension once a day during 24 days.
RESULTS. The use of BI-V against the background of individualized regimens of AMBT in children and adolescents with  MDR/Rif-TBP increased the effectiveness of treatment, contributed to the disappearance of symptoms of intoxication, the resolution of infiltration foci and the healing of decay cavities in system of immune protection, which contributed to the shortening of the inpatient stage of treatment, while maintaining a high therapeutic effectiveness (“cured” ‒ 92.8 %)  and the formation of small residual changes in the lungs in the majority (89.3 %).
CONCLUSIONS. When using combined complex AMBT with Bdq, Dlm and BI-V, high therapeutic efficiency was observed  in most patients (92.8 %).
KEY WORDS: multiple drug-resistant pulmonary tuberculosis, treatment, bedaquiline, delamanid, BI-V, children, adolescents

UDC  616.375-008.64-07-053.2

Abstract. Cardiac autonomic neuropathy (CAN) is closely associated with an approximately five-fold increase in the risk of cardiovascular mortality in patients with diabetes mellitus (DM). Impaired autonomic function of the cardiovascular system in DM, which leads to the development of CAN, can be accompanied by coronary artery ischemia, heart rhythm disturbances, “silent” myocardial infarction, severe orthostatic hypotension, and sudden cardiac death syndrome. The article provides an analysis of literature data on the impact of glycemic variability (GV) on diabetic CAN development. This review analyzed the possible relationships between GV in people with diabetic CAN. In particular, the issues related to glycemic control and CAN, the link between GV and CAN in diabetes were analyzed. Unsatisfactory glycemic control and uncontrolled glycemic status are considered the main risk factors for chronic complications of DM, in particular CAN. An increase of GV is associated with a higher risk of chronic complications of DM, cardiovascular risk, all-cause mortality and morbidity. The clinical trial results demonstrated that time in range might be a promising metric for assessing glycemic control and prognosis of diabetic complications. This review is based on a search in PubMed and MEDLINE, Scopus, BIOSIS, EMBASE, Google Scholar and Springer Online Archives Collection. The following keywords were used: glycemic variability, cardiac autonomic neuropathy and diabetes mellitus. Research findings missed by the web search have been identified through a manual search of the bibliography of publications. CAN is one of the frequent long-term complications of DM, and reasonable control of GV may be necessary for its prevention. Determination of GV may have advantages for predicting future complications of DM in clinical trials and practice. The association of autonomic dysfunction and glucose levels, insulin resistance, and HbA1c variability suggest further research to reduce chronic complications development. Further investigation is needed to study the mechanisms of GV and evaluate them as therapeutic targets in the treatment of patients with T2DM.
Keywords: diabetes mellitus; cardiac autonomic neuropathy; glycemic variability

UDC: 611.37.018.72:615.212.7].08

Use of narcotic drugs in clinical practice for the purpose of obtaining analgesic and anti-inflammatory effects requires a comprehensive morphological study of the peculiarities of structural arrangement of organs under the conditions of exposure to opioids. The aim of our study was to establish the peculiarities of restructuring of the structural components of the pancreas under the conditions of long-time exposure to opioids in the experiment. The study included 24 adult laboratory white male rats. The test animals were divided into 2 groups, the experimental and control ones. The experimental animals were daily administered narcotic analgesic nalbuphine intramuscularly (once a day in the same interval) for four weeks, and the control animals were administered saline solution. The following research methods were used: bloodstream injection followed by translucence of sections of the pancreas and their
photographing, morphometry of the vessels of the pancreatic hemomicrocirculatory bed, histological, histochemical studies and electron microscopy of the pancreas, blood biochemistry test; statistical processing of the study results using a software package. After four weeks of opioid exposure, lesion of the pancreatic parenchyma microstructure was observed, manifested by swelling and infiltration by lymphocytes and macrophages of the pancreatic connective tissue stroma, disorganization of the exo- and endocrine parts of the parenchyma, deep destructive changes in the excretory ducts, as well as in the vessels of the hemo- and lympho-microcirculatory bed of the pancreas. At the ultrastructural level, deep dystrophic changes of exo- and endocrinocytes of the pancreas were identified, in particular, loss of regular shape, karyopyknosis and karyorrhexis of the nuclei, swelling and clearing of cytoplasm, development of microcystic degeneration of cells, loosening and disorganization of the basement membrane, which can result in impairment of exocrine function of the pancreas and complication of the process of secretory granules excretion into the lumen of the intercalated ducts. A significant decrease, compared to the control group, in the diameter of arterioles, density of exchange vessels network, as well as increase in the diameter of venules, the indicator of trophic activity of the tissue, are the evidence of destructive changes in the hemomicrocirculatory bed of the pancreas under the effects of nalbuphine. Significant changes in blood biochemistry parameters (alanine aminotransferase, aspartate aminotransferase) after a four-week administration of nalbuphine are illustrative of the process of pancreatic tissue destruction. Therefore, four-week administration of opioid leads to profound changes in the micro- and ultrastructure of the pancreas, vessels of its hemomicrocirculatory bed, and blood biochemistry parameters in experimental white rats.
Keywords: pancreas, structural changes, opioid, experiment.