THE RELATIONSHIP BETWEEN TYPE-2 DIABETES AND TUBERCULOSIS.

According to the experimental and clinical investigations, innate and adaptive immune disorders play a significant role in T2-D subjects to become more susceptible to TB. It was shown that the functions of neutrophils, macrophages, NK cells and other components of innate immunity areis markedly compromised by metabolic disorders in T2-D. The number of evidences suggests that reduction in TH1:TH2 cytokines ratios may have significant influence on susceptibility of TB infection in T2-D subjects. Hormonal changes in T2-D also may increase susceptibility to TB, including 2 hormones -ghrelin and leptin that are involved to in controlling blood glucose levels related to malnutrition during TB. According Based on the experimental and clinical results resistin, being a key molecule that links obesity and TB2-D, is considered as a protein contributing contributor to the development of insulin resistance, being a key molecule that links obesity and TB2-D. Subjects with T2-D showed higher levels of resistin in serum associated with reduced possibility of human macrophages to enhance the production of reactive oxygen species (ROS) in vitro against a challenge with TB. Immunological impairment has an important role in susceptibility to TB infection for patients with T2-D. It has been revealed that IFN-y and IL-22 markedly discriminate diabetes from nondiabetic individuals. It was also established that aside from this many cytokines such as IL-17A, IFN-B, TNFα, IL-10, IL-18, IFN-Y and IL-22 are the most significant and consequently potentially related to the effects caused by diabetes caused effects in the pathogenesis of active pulmonary TB. The endothelial system plays significant role in the pathogenesis and progression of TB infection. It was demonstrated that endothelin "B" receptor antagonist leads to vasoconstriction precluding inflammatory cell infiltration in lung tissue, suggesting that ET-1 proinflammatory action involves ET "B" receptor. It was also shown that sputum endothelin-1 level is associated with active pulmonary tuberculosis and effectiveness of treatment. Reduction ins sputum ET-1 level has significant role in the assessment of anti-tuberculosis treatment efficacy. Alterations in microbiota in T2-D subjects may influence on immunity against TB infection. As it was established the amount of bacteria producing short-chain fatty acids (SCFA) markedly decrease in T2-D, and treatment with SCFA reduced induction of TFN-α, IL-10 and IL-17 cytokines in contrast to IL-6, IFN-y and IL-22, without modification of their induction after using of SCFA. Vitamin "D" deficiency in T2-D may also play a role ion the immune response against TB. A number of evidences suggest the correlation between its diminished levels and TB or TB-T2-D. In conclusion it is suggested that different risk factors, including immunological and hormonal changes as well as alterations in different cytokine production and microbiota, endothelial dysfunction and vitamin "D" deficiency are the main contributors leading to comorbidity of T2-D and in TB.

PROGNOSTIC VALUE OF PLASMA MYELOPEROXIDASE LEVEL'S AND ECHOCARDIOGRAPHIC DETERMINANTS IN CHRONIC HEART FAILURE PATIENTS.

The aim of current study was to investigate the level of Myeloperoxidase (MPO) in chronic heart failure patients with different severity and find the correlation with cardiac structural and functional markers and disease outcome. Initially eighty-six patients with different stages of CHF and ten healthy persons were included in our study. Excluded criteria were myocardial infarction or other concomitant acute diseases, renal failure (creatinine >250 µmol/L) in past 3 months. All patients underwent ECG, echocardiographic evaluation, anthropometric and other clinical examination, as well as plasma samples were collected for further analysis. MPO level (ng/ml) was measured by ELISA method, hs-CRP (mg/L) was measured by turbidimetric immunoassay and Leukocyte level (109/L) - by flow cytometry. Echocardiographic studies were performed using standard methods by parasternal and apical view. Statistical analyses were performed using IBM SPSS Statistics 16.0. After 6 month follow up we investigate our research primary outcome (mortality). The data were collected by telephone follow up from patients or members of family. Collection of information had been became possible in 79% of total cases (68 patients), from which 10 patients died: 8 cases were cardiovascular mortality, 1 case - suicide and 1 case from cancer. We found that MPO levels in the patients with CHF (mean value 9.3±7) are different from control group (mean value 4.19±2). MPO correlates with HF severity. MPO significantly were elevated in mortality group p<0,007 , as the level of hs-CRP p˂ 0.001. Changes of RV (right ventricule) sizes from normal ranges also were associated to worse outcome ( p<0.005). Depending on our data certain level of MPO (˃7.1 ng/ml) in studied patients and increased RVDD have independent importance for identification of patients with worse outcome.

INFLUENCE OF NUTRITIONAL STATE ON OUTCOME IN PATIENTS WITH CHRONIC HEART FAILURE.

The aim of present study was to investigate the nutritional status of patients with cronic heart failure and find correlation with disease outcomes. Initially 86 patients with different stages of CHF and 10 healthy persons were included in our study. Exclusion criteria were myocardial infarction or other concomitant acute diseases, renal failure (creatinine >250 µmol/L) in past 3 months. All patients underwent ECG, echocardiographic evaluation, clinical examination, as well as plasma samples were collected for further analysis. MPO level (ng/ml) was measured by ELISA method, hs-CRP (mg/L) was measured by turbidimetric immunoassay. The serum albumin level (g/L) was used as an indicator of protein reserves. The serum total cholesterol level (mg/dL) was used as a parameter of caloric depletion. For both tests colorimetric method were used. Statistical analyses were performed using IBM SPSS Statistics 16.0. After 6 month follow up we investigate CHF outcome (mortality). The data were collected by telephone follow up from patients or members of family. Collection of information had been became possible in 68 (79%) of cases. We found that MPO correlates with HF severity. 10 mortality cases were indentified, from which 8 patient died from cardiovasvular (CV) cause, all of them were males. In cardiovascular mortality group, the markers of inflammation (MPO, hs-CRP) were elevated significantly while markers of protein-energetical malnutrition were decreased (total protein, albumin, Total Colesterol, LDL-Cholesterol, HDL-Cholesterol). In our study malnutrition and inflammation are important predictors for assessment of disease prognoses in CHF patients. Additional management is necessary for these patients as well as further researches for elaboration of new treatment strategies.

[Peculiarities of behavior of offspring of rats-ambidexters after surviving vital stress].

Psychogenic trauma inflicted to mothers (Wistar rats) during pregnancy is more tragic for establishment of psychoemotional functions in offspring than in the rat pups whose mothers survived prior to pregnancy the stress connected with threat of life. The "antenatal stress" causes in the one-month-old offspring the depression-like behavior, while the stress one month prior to conception--the increased anxiety. Disturbances of the integral behavior in the test "open field" can be caused both by the acute psychogenic trauma of mothers and by its delayed consequences. The sharp impoverishment of behavior and the more pronounced psychoemotional disturbances are realized in female individuals regardless of the terms of the action. In the male offspring the vital stress during their mothers' pregnancy produces the rougher behavioral disturbances than stress prior to conception.

Neurohumoral regulation in children with idiopathic scoliosis.

Biotesting of blood serum in children aged 8-15 with adolescent idiopathic scoliosis (0°-60° by Cobb) showed the change of neurohumoral regulation in comparison with the age norm. The degree and direction of changes in the biotesting give the indication of the progression of spinal deformity. The effectiveness of treatment can be judged by control biotesting.

Clinical outcomes among patients with tuberculous meningitis receiving intensified treatment regimens.

SETTING: National Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.OBJECTIVE: To determine clinical outcomes of patients with tuberculous meningitis (TBM) treated with an intensified regimen including a fluoroquinolone (FQ) and an injectable agent.DESIGN: Prospective cohort of patients aged ≥16 years initiating treatment for TBM at the NCTLD from January 2018 to December 2019. Treatment outcomes and neurologic disability at 1, 6 and 12 months after treatment initiation were assessed.RESULTS: Among 77 patients with median follow-up time of 363 days (IQR 269-374), 97% received a FQ, 62% an injectable agent, 44% linezolid and 39% a carbapenem. Fifty-seven patients (74%) successfully completed treatment, 2 (2.6%) had treatment failure, 6 (7.8%) died, and the remainder (12%) were lost to follow up. Among 11 patients treated for multidrug-resistant TBM, the median follow-up time was 467 days and one patient (8%) died. Regarding neurologic outcomes, 14/76 (18%) patients had Modified Rankin Scores of 0 at baseline, improving to 85% (56/66) and 94% (47/50) at 6 and 12 months, respectively.CONCLUSION: Intensified multidrug treatment regimens including a FQ and an injectable agent in all patients and newly implemented drugs in patients with multidrug-resistant TBM resulted in low mortality and favorable neurologic outcomes.

[Polyunsaturated fatty acids prevent the development of locomotor disturbances caused by changes in the neurohumoral background in rat pups].

The present study shows the effectiveness of using polyunsaturated fatty acids in pregnant rats in order to prevent behavioral alterations in neonatal rats caused by the action of the pathogenic peptide factors of blood serum with perinatal damage of the central nervous system.

[EXISTENTIAL ORGANIZATION OF BRAIN BIOELECTRICAL ACTIVITY OF THE OFFSPRING OF RATS AFTER VITAL STRESS].

An association was found between severity of behavioral disturbances in the offspring of rats that survived the stress, and changing spatial-temporal organization of the ECOG. The proportion of synchronous activity in the right frontal and left occipital regions with respect to the right nape, and between the frontal leads increases with the minimum deviations of behavior. The proportion of ahead activity increased in frontal leads; reduced the share of lagging and an increasing proportion of synchronous bioelectrical activity in relation to the right occipital region in case of serious disorders of behavior.

Lateralization of brain trauma in female Wistar rats determines the immune and neurological status of offspring.

Unilateral trauma to the sensorimotor cortex in ambidextrous maternal female rats decreased the resistance of their offspring, as indicated by a reduction in the functional activity of natural killer cells. Offspring rats showed T-cell immunodeficiency regardless of the lateralization of the trauma in their mothers; this was more severe after right-sided trauma (both mature and immature T-lymphocytes were affected). The EMG pattern of evoked responses in offspring rats changed according to the lesions evoked by unilateral trauma in their mothers (in the muscles responsible for postural asymmetry). Cruder movement disturbances were also seen in offspring after right-sided trauma in mothers. Right-sided organic damage to the sensorimotor cortex in mothers evoked marked increases in negative emotionality and decreases in the motivation of orientational-investigative behavior in one-month-old offspring rats in the "open field" test.

[The embryotoxic effect in rats exposed to the blood serum of newborn infants tested for the presence of transfer factors]. / Embriotoksicheskii éffekt u krys pri vozdeistvii syvorotkoi krovi novorozhdennykh detei, testiruemykh na nalichie transfernykh faktorov.

Pregnant rats (day 14 of gestation) received intraamniotic injections of newborn human serum. Transfer factors (TF) present in injected serum produced significant embryotoxic and teratogenic effects, as well as changes in coordination of motor activity (EMG) in newborn rats. The extent of embryological disturbances and the motor activity of 33- to 34-day old recipient rats depend on TF concentration (at serum dilution 1:2) and on the state of infant's motor functions ("normal" group and "risk" group). The results obtained allow to objectively determine the pathogenic effect of serum TF on embryotoxicity and formation of motor coordination in the donor infant.

[The locomotor and spatially oriented behavior of normal rat pups and in experimental pathology]. / Lokomotornoe i prostranstvenno-orientirovochnoe povedenie krysiat v norme i pri éksperimental'noi patologii.

Breach of locomotor functions and spatially oriented behaviour of rats' cubs after intraamniotic administration of the blood serum of children was shown to depend on the ontogenetic maturity and motor disturbances of donors. Injections were carried out on 14-th day of rats pregnancy.

[Unilateral injury of sensorimotor cortex of the dominant or subdominant hemispheres of rats-mothers and emotional behavior of their offsprings in the "open field"]. / Unilateral'noe povrezhdenie sensomotornoi kory dominantnogo i subdominantnogo polusharii mozga krys-materei i povedenie potomstva v "otkrytom pole".

Neurohumoral disorders in mothers caused by brain injury, infection, hypoxia, and other pathological factors result in motor and psychoemotional disorders in children. Emotional behavior of 30-day-old offsprings of female rats with unilateral sensorimotor brain injury was studied in the "open field". Individual behavior was estimated (the probability of certain acts and significant transfers between them). Behavioral disorders in rat offsprings depended on the side (left of right) of mother's brain injury and "handedness". The right-side mother's injury turned to be more deleterious. Behavioral alterations were stronger in offsprings of ambidextral and left-handed females than in those born by right-handed males with the same sensorimotor injury.

[Detection of movement disorders in newborn infants by using infants' blood serum in experimental models]. / Vyiavlenie dvigatel'nykh rasstroistv v period novorozhdennosti priemami biotestirovaniia syvorotki krovi detei na éksperi- mental'nykh modeliakh.

A method of early diagnosis of motor disorders of the central genesis in neonates within the first to the third days of life was elaborated in experimental models for estimating the status of the motor apparatus. The experiments were made on spinal (Th3-Th5) albino noninbred rats used as recipients, in which spontaneous and electric stimulation-induced EMG activity of the antagonists muscles of the hind limbs was recorded before and after intralumbar administration of donors' blood serum. The presence of motor pathology in a donor child is judged from the changes in the EMG parameters after administration of blood serum. The method enables revealing motor disorders in neonates even in cases where the clinical examination does not provide any conclusive answer.

[Interaction of the motor centers in posture-evoked asymmetry]. / Vzaimodeistvie dvigatel'nykh tsentrov pri vyzvannoi poznoi asimmetrii.

The EMG of hindlimb muscles was studied in spinal cats in resting and in evoked responses prior to and after modelling posture asymmetry with brain extracts obtained from donor rats whose cortical and cerebellar motor areas were partially lesioned. After the extract administration, slow and diverse changes occurred in the EMG amplitude whereas a constant level of activity was only maintained for limited periods (4-10 min). The most frequent patterns of interaction among hindlimb muscles were revealed and the character of evoked responses was shown to depend on the initial spontaneous pattern. The different EMG patterns in spinal animals seem to be due to a "mosaic" effects of interneurons, the posture of asymmetry being related to disturbance of interaction among the interneurons.

[The phenomenon of the replication of ontogenetic immaturity in adult cats caused by the cerebrospinal fluid of kittens]. / Fenomen vosproizvedeniia ontogeneticheskoi nezrelosti u koshek, vyzvannyi likvorom kotiat.

Studies have been made on the electrical activity of muscles in the hindlimbs in kittens and adult cats before and after injection the liquor from 10-, 21-day and 1-month kittens into the lumbar part of the spinal cord. Analysis was made of the EMG at rest and that of the evoked reactions. It was shown that EMG of adult cats after injection of kitten liquor attained the pattern typical of the donor. The data obtained indicate the presence in kitten liquor of biologically active substances which account for the level of regulatory relationships. Transfer of these substances to adult animals results in the formation of a new level of coordinations of movements which corresponds to immature organism.

[The effect of amniotic fluid taken from women in labor on the morphofunctional development of fetal and newborn rats]. / Vliianie amnioticheskoi zhidkosti, vziatoi u zhenshchin vo vremia rodov, na morfofunktsional'noe razvitie plodov i novorozhdennykh krys.

Amniotic fluid from women was injected intra-amniotically to rats at the 14th day of pregnancy in a dose 0.3 ml. Morphological and functional parameters of embryonic development of rats and EMG activity of rat puppies at the age of 30-34 days differed from control ones with respect to the degree of maturity and motor disturbances of newborn babies. The data obtained reveal not only evident but also masked forms of motor pathology which was observed in children later, namely to 6-9 months. Chronic motor pathology in rat puppies was unilateral with central motor disturbances in babies being directly related to the degree of these disturbances.

[A neuromorphological analysis of the motor area of the cerebral cortex in rat pups subjected to prenatal exposure to normal and pathological blood serum]. / Neiromorfologicheskii analiz motornoi oblasti kory mozga krysiat, podvergshikhsia prenatal'nomu vozdeistviiu normal'noi i patologicheskoi syvorotki krovi.

Morphological quantitative and qualitative analysis of the pyramidal neurones in the motor cortex of rat puppies after administration of the blood serum from human donors with central motor disorders reveals the dependence of the quality and quantity of neurones from the effect of corresponding blood sera. Pathologic blood serum decreases the number and induces degradation of dendritic organization of the pyramidal neurones. The effect of the blood sera on quantitative and qualitative properties of the pyramidal neurones in rat puppies depends on the age of donor infants with central motor disorders. Blood serum from newborn babies with motor dysfunctions significantly decreases the number of labeled pyramidal neurones and results in degradation of dendritic organization, whereas sera from 11-13-year infants only insignificantly affect these characteristics.

[Prediction of potential motor disorders in babies from neonatal serum biological test findings]. / Prognozirovanie vozmozhnykh dvigatel'nykh narushenii u detei po rezul'tatam biotesta syvorotki krovi novorozhdennykh.

To predict motor activity in the newborn, electromyographic (on rats) and ultrastructural (on chick embryos) studies were performed after administration of donor babies' sera taken in the first days of life. Morphological and electromyographic parameters were compared with late clinical symptoms. A rating schedule was developed with regards to biological test results, which allows motor disorders to be detected in the newborn.

[Features of an existential organization of a bioelectric activity of the brain at posterity from rats with a lateral injury of the brain].

Features of the existential organization of a bioelectric activity of a brain at posterity from rats with a lateral injury of the brain were investigated. The EEG analysis revealed in one month animals significantly increased the proportion of advanced and lagging decrease in the activity of the right frontal derivation towards the right occipital region. Change between structural ties in terms of the rats were correlated with the severity of behavioral disorders in the test "open field" (OF). The most significant change in the existential organization of a bioelectrical activity (the reduction of synchronous communications between the frontal derivations) recorded in rats with severe conduct disorder compared with animals of the same groups, in which the behavior was not significantly different from the norm. The violation of the behavior in the test OF was accompanied by a decrease in synchronous activity between the left frontal and right occipital region or the decline in the anticipatory activity in the right frontal region in relation to the right occipital region. By maintaining the integrity of the behavior of these parameters were increased in comparison with an intact control.

[Influence of maternal factor on motor behavior and lipid turnover in rats exposed to severe psychoemotional stress].

Adverse condition of rat development during the prenatal period (rearing by mother survived brain injury) or during the early post-natal period (cross fostering), causes impairment of motor behavior and a lipid turnover in adult rats. Such rats under severe stress showed decrease of adaptation (as expressed or low indexes of motor impellent behavior and lipid metabolism) in comparison with rats that were grown up by own mother. The psychoemotional stress caused the most expressed deficient behavior in males that were grown up by mothers with brain injury (decrease in serum level of HC and HDL and depressively - similar behavior).