Effects of Levofloxacin on Blood Lymphocyte Apoptosis in Patients with Pulmonary Tuberculosis: an In Vitro Study.

The effects of a fluroquinolone levofloxacin on apoptosis of peripheral blood lymphocytes from patients with infiltrative pulmonary tuberculosis were studied in vitro. It was found that levofloxacin stimulated apoptotic cell death in tuberculosis. Addition of levofloxacin to cell suspension from patients with drug-susceptible form of tuberculosis led to an increase in the number of CD95+ and AnnV+ lymphocytes. In patients with drug-resistant form of tuberculosis, only the number of apoptotic lymphocytes, but not the count of CD95+ cells increased under these conditions.

Expression of Galectins-1 and Galectin-3 in Stomach and Colorectal Cancer with Tissue Eosinophilia.

We analyzed the expression of galectin-1 and galectin-3 in tumor tissue in stomach and colorectal cancer with and without tissue eosinophilia. Low expression of galectin-3 was detected in all patients with malignant gastrointestinal tumors irrespective of the presence of eosinophilia. Low expression of galectin-1 was detected only in patients with gastrointestinal cancer associated with eosinophilia. Association of galectin-1 expression with eosinophilic infiltration of the tumor tissue in stomach and colorectal cancer was detected.

Comparative Evaluation of ß-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules.

We compared the results of gene molecular and immunocytochemical studies of ß-catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/ß-catenin complex leading to switching from adhesion function of ß-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-ß-catenin interactions in the mechanisms of malignant transformation of follicular epithelium.

[ß-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells].

The article presents the data on the structure and mechanisms of ß-catenin functioning. The basic aspects of the role of ß-catenin in malignant transformation have been studied at various tumors. Primary structure of ß-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al. This interaction is the base for ß-catenin's intracellular multi-functioning. The review presents data on the participation of ß-catenin in the mechanisms of adhesion, regulation of RNA metabolism, formation contacts with the cytoskeleton and its role in the canonical Wnt signaling pathway, marked examples pro-inflammatory and anti-inflammatory effects of ß-catenin. The ß-catenin involvement in malignant transformation and progression of certain tumors is not in doubt. The data on the changes in ß-catenin expression in the given examples of colon cancer, prostate cancer, different forms of thyroid cancer and hepatocellular carcinoma are presented with the prospects of its use as a marker and a predictor of malignant transformation. Continued research in this area will not only make use of ß-catenin as a potential predictor of malignant tumors, but also to develop approaches to targeted therapy.

[Clinical and immunological comparisons of therapeutic regimens for corneal infiltrates secondary to adenoviral keratoconjunctivitis].

UNLABELLED: The problem with post-adenoviral corneal infiltrates is that they cause a significant and persistent decrease in visual function, while corticosteroids in monotherapy bring only temporary improvement. AIM: to perform a comparative evaluation of topical corticosteroids and 0.05% cyclosporine A efficacy in the treatment of post-adenoviral corneal infiltrates on the basis of clinical presentation and local cytokine status. MATERIAL AND METHODS: The study involved two groups of patients after adenoviral keratoconjunctivitis: group 1 (25 patients, 45 eyes) were prescribed a diminishing regimen of corticosteroid eye drops for 12 weeks and corneal protectors; group 2 (24 patients, 42 eyes) received the same treatment as described above plus topical 0.05% cyclosporine A for 6 months. The follow-up period was from 6 to 12 months. Visual acuity measurements, biomicroscopy, and pneumatic tonometry were performed at months 1, 3, and 6. Local cytokine status was assessed by studying cytokine gene expression in cell culture from conjunctival scrapings and cytokines levels in the supernatant. The tests were done before the beginning of the treatment in both groups, at month 1 in group 1, at month 4 in group 2 (i.e. in a month after the cessation of dexamethasone) and also in a group of healthy volunteers (30 persons, 30 eyes). RESULTS: Long-term combined anti-inflammatory therapy with corticosteroids and 0.05% cyclosporine A in patients with post-adenoviral corneal infiltrates has yielded positive clinical results, including a persistent increase in visual acuity and complete resolution of corneal opacities (92.8%). In addition, we revealed a correlation between local cytokine status changes and clinical results. CONCLUSION: The proposed therapeutic regimen enabled complete suppression of residual interferon-α antiviral activity, an increase in interleukin-4 that regulates local humoral immunity, and a decrease (down to a complete suppression) in anti-inflammatory interleukin-2, which is responsible for activation of cell-mediated immunity, thus, resulting in resolution of the immune-mediated inflammation in the cornea.

The effects of galectin-1 on the gene expression of the transcription factors TBX21, GATA-3, FOXP3 and RORC.

CD4(+) T cells orchestrate the immune response by differentiating into T helper (Th) or regulatory (Treg) cell subsets that secrete distinct sets of cytokines. They also play a critical role in the pathogenesis of autoimmunity, asthma, allergy and, likely, cancer. The mechanisms involved in the regulation of CD4(+) T cell homeostasis by galectin-1 remain poorly characterized. To investigate whether galectin-1 modulates the differentiation of CD4(+) T cells, the effects of galectin-1 on the mRNA expression levels of TBX21, GATA-3, FOXP3 and RORC in activated peripheral blood mononuclear cells were examined. The expression levels of GATA-3 and FOXP3 mRNA were up-regulated after treatment with 1.0 µg/ml galectin-1 and were unchanged (for GATA-3) or slightly elevated (for FOXP3) compared with untreated cells when 2.0 µg/ml galectin-1 was added. At the same time, at both concentrations of galectin-1, we observed reduced TBX21 and RORC mRNA expression levels. These findings support the concept that galectin-1 skews the differentiation of CD4(+) T cells towards Th2 and Treg cells.

[Use of cyclosporine 0.05% in various ocular surface disorders].

It is proved that chronic ocular surface inflammatory disease (including allergic blepharitis, recurrent chalyazia, punctuate keratitis, recurrent herpetic corneal erosions, late stages of adenoviral keratoconjunctivitis, etc.) takes part in the development of secondary dry eye syndrome (DES). However, therapies for inflammation-induced impairment of tear production do not provide long-term control of inflammatory process. Cyclosporine 0.05% eye drops are an option. Their effect is well-studied in foreign practice. Local application experience of cyclosporine 0.05% eye drops was summarized at a meeting of the Russian expert group on DES and conclusions were made on their effectiveness in treatment of dry eye syndrome associated with certain ocular surface inflammatory disorders, such as allergic blepharoconjunctivitis, late stages of adenoviral keratoconjunctivitis, and others.

Effect of galectin-1 on apoptosis of CD4(+) lymphocytes differentiated in vitro towards regulatory T cells.

We studied the effect of galectin-1 on apoptosis of CD4(+) lymphocytes intact and in vitro differentiated towards regulatory T cells. An increase in the content of apoptotic CD4(+) lymphocytes was observed after exposure of intact cells with 15 ng/ml galectin-1 and after exposure of regulatory T cells with 10 and 15 ng/ml galectin-1. Apoptosis of regulatory T cells induced by galectin-1 was accompanied by an increase in the content of proapoptotic protein Bad.

[Regulation of the genes expression of CD4+ T-lymphocytes differentiation transcription factors by galectin-3 in vitro].

Now a number of CD4+ T-lymphocytes, known as Th1, Th2, Treg and Th17, is currently identified and well- studied. The methods basing on the targeted regulation of differentiation process of the Th-lymphocytes that carry out the immune response polarization attract an attention of scientists dealing with a correction of immune-mediated. In the present study, endogenous beta-galactoside-binding protein of the lectin family, galectin-3, was investigated as a regulator of T-cell homeostasis. A galectin-3 is known to be actively produced by tumor cells in malignant transformation and able to influence the processes of signal transduction, cell-cell cooperation and the implementation of programmed death. As cell differentiation processes are directly connected with the regulation of gene expression, we investigated the effect of recombinant galectin-3 on expression of mRNA of transcription.factors, which guide the differentiation of CD4+ lymphocytes. The study was performed on peripheral blood mononuclear cells of healthy individuals. The gene expression levels were evaluated by a real-time PCR. In the experiments in vitro, it has been first found the recombinant galectin-3 (0.5 mg/mL) up-regulating the expression of transcription factors Gata-3 and Rorc mRNAs and down-regulating the mRNA expression of transcription factors T-bet and FoxP3. Up to a concentration of 1 mg/mL recombinant galectin-3 stimulates Th-cells by dose-dependent manner, whereas at higher concentrations stimulating effect weakens, and inhibiting action starts prevailing. Thus, one can suppose that galectin-3 through regulation of lymphocytes differentiation promote development of allergic, autoimmune and neoplastic diseases that allows us to consider the galectin-3 as a.potential target for therapy of these diseases.

[Comparative morphological study of thyroid gland in mammalian animals and man].

The objective of this study was to examine the morphological peculiarities of the thyroid gland in animals of different mammalian orders and in man at both macroscopic and microscopic level. 304 specimens of the thyroid gland obtained from the animals of 13 species and 5 mammalian orders and man, were studied. At the macroscopic level, the changes of lobar shape, presence and structural peculiarities of the isthmus, and its relative size were analyzed. At the microscopic level, the following parameters were determined in comparative aspect: the volume fractions of major structural components, the indices of activity, sclerosis and colloid accumulation, the standardized follicular profile shape and size, follicular epithelium height. With the increase of size of the species studied, a tendency was found for the increase of thyroid lobe width and the appearance of parenchymal isthmus, connecting the lobes. At the microscopic level, the variability of follicular profile shape and size was found to increase from small rodents to artiodactyls and man. According to morphological indices, the activity of the thyroid gland in artiodactyls and man was decreased as compared to that one in the other mammalian species.

[Age-dependent changes of the autonomic neurons expressing vanilloid TRPV1 receptors].

Expression of vanilloid receptors in sympathetic and afferent ganglionic neurons was studied in rats of different ages (newborn, 10-day old, 20-day old, 30-day old, 60-, 180-day old) using immunohistochemical methods. The results obtained indicate that the majority of the afferent neurons in the nodose ganglion of vagus nerve (GNVN) and in the spinal ganglia (SG) were TRPV1-positive from birth onwards. The percentage of neurons containing TRPVT receptors in SG slightly increased with age up to 30 days postnatally. In the GNVN, the percentage of TRPV1-positive neurons was higher in comparison with the SG in all age groups. The vast majority of the sympathetic neurons were TRPV1-positive from birth onwards, and the percentage of TRPV1-immunoreactive neurons substantially decreased during further development. In 20-day old and older animals, we observed only few TRPV1-immunoreactive neurons in sympathetic ganglia. Finally, the percentage of neurons containing these types of neurons, become similar to adult animals to the end of the first month of life.

[Age factors in the background electrical activity of the superior cervical ganglion neurons in rats].

Background discharges of single neurons were studied from the superior cervical ganglion in newborn, 10-, 20-day-old, 1-, 2- and 6-month-old rats. In all age groups, the largest proportion of neurons exhibited aperiodic activity. The percentage of neurons with respiratory rhythmic was less. In newborn and 10-day-old rats, the frequency of discharges was low. Discharge frequency increased in 20-day-old rats. In 20-day-old and more adult rats, we found neurons bursting with cardiac frequency. The means of frequency did not statistically differ in 1-, 2- and 6-month-old rats. Thus, the pattern of neuronal activity is formed during the development in 20-day-old rats. Final maturation of this pattern is observed in 1-month-old rats.

[Morphological features of the rat stellate ganglion during early postnatal development].

The aim of this work was to study the anatomical characteristics of the stellate ganglion (SG) and the morphometric characteristics of its neurons in rats of different age groups (newborn, 10-, 20-, 30-, 60- and 180-day-old) using anatomical and histological methods. The results obtained indicated that in rats since birth there were three variants of branch origin from the medial margin of SG. No differences were observed in these variants between right and left SG. The sizes of both SG and its neurons increased during the first two months of postnatal development. The density of neurons in SG sections decreased from the moment of birth until the six months of age. The number of SG neurons did not change significantly in the postnatal ontogenesis. Thus, SG in rats is anatomically formed by the moment of birth, while the sizes and morphometric characteristics of SG neurons become finally stabilized by the second month of age.

[Modulatory effect of isoniazid and rifampicin in vitro on cytokine secretion in pulmonary tuberculosis].

The effects of isoniazid and rifampicin on the peripheral mononuclear production of IL-2, IL-12, IL-10, IFN-gamma, and TGF-beta were evaluated in patients with infiltrative pulmonary tuberculosis. Irrespective of the susceptibility of the causative agent to the essential antituberculous drugs, rifampicin was ascertained to initiate increased IL-2 secretion and to reduce the generation of IL-12, IFN-gamma and TGF-beta. Isoniazid suppressed the mononuclear leukocytic production of IFN-gamma in drug-sensitive pulmonary tuberculosis, and conversely, stimulated it in the drug-resistant type. Rifampicin showed a more significant negative effect on mononuclear cytokine-producing activity. In drug-resistant pulmonary tuberculosis, the imbalance of spontaneous, protein- and drug-induced mononuclear secretion of cytokines was established to be more pronounced than in drug-sensitive tuberculosis.

[Evaluation of the effects of antituberculous drugs on the cytochemical status of lymphocytes in vitro].

The effects of basic drugs of chemotherapy for tuberclosis, such as isoniazid and rifampicin, on the activity of the most important mitochondrial enzymes of lymphocytic energy metabolism were studied in patients with infiltrative tuberculosis and healthy donors. The authors detected the significantly inhibited activity of succinate dehydrogenase and the redistribution of lymphocytic populations with the increased proportion of cells with the low and high activities of the enzyme. The more significant negative effect on the lymphocytes of patients with tuberculosis was observed when rifampicin was administered. In patients with pulmonary tuberculosis, the suppressed enzymatic activity of peripheral blood lymphocytes was shown to be more pronounced when the cells were incubated with rifampicin and isoniazid for 2 hours than for 1 hour.

[Role of cytokines in the modulation of lymphocytic subpopulational composition in patients with pulmonary tuberculosis].

The parameters of the lymphocytic CD-population composition and the production of cytokines in the cell cultures of peripheral blood mononuclear cells were studied in patients with infiltrative pulmonary tuberculosis. A marked reduction in the relative and absolute count of CD3+ and CD4+ lymphocytes and an increase in the level of CD8- and CD16-positive cells were established in both drug-sensitive and drug-resistant types of the disease. A significant increase in the production of IL-12 and a reduction in the spontaneous elaboration of interferon-gamma were observed in all the examinees. Addition of lipid and protein myobacterial antigens (Beijing strains) caused a notable decrease in the generation of the study cytokines as compared with the respective parameters in healthy donors and their basal secretion irrespective of the type of a tuberculous process.

[The characteristics of the interferon system parameters in typologically different groups of patients with borderline mental disorders during treatment]. / Kharakteristika nekotorykh parametrov sistemy interferona v tipologicheski razlichnykh gruppakh bol'nykh s pogranichnymi psikhicheskimi rasstroistvami v protsesse lecheniia.

Lymphocyte gamma-interferon production and levels of serum interferon were studied in 94 patients with borderline psychiatric disorders on treatment. It was shown that parameters of interferon system in the acute disease period and their dynamics through the treatment depend on typological features of personality and initial level of interferon production. The patients with aggressive features of personality in acute disease exhibit significantly higher levels of serum interferon than those in patients with submissive features which drop after recovery. The same tendency occurred in hysterical patients (hystero-expressive and hystero-impressive types). These findings may be due to different reaction of immune system to chronic emotional stress in different types of personality.

[Comparative analysis of indicators of the immune status of population of the Eastern regions of the USSR]. / Sravnitel'nyi analiz pokazatelei immunnogo statusa naseleniia vostochnykh regionov SSSR.

Altogether 1,500 healthy residents of seven cities situated in the Asian part of the USSR were examined. In Novosibirsk, Tomsk, Tyumen, Norilsk, Magadan, Yakutsk and Ussuriisk, the people were examined for the blood levels of T and B lymphocytes, the ratio of regulatory subclasses of T lymphocytes, the concentration of IgG, IgM and IgA, and for the content of immune complexes. Analysis was made of the general and regional regularities in changes seen in the immune system depending on climatic and geographic factors. Parameters of the populations similarity in the regions with different environmental conditions were delineated.

[Epidemiology, clinical aspects and prevention of borderline conditions in the regions of Siberia and Far East]. / Epidemiologiia, klinika i profilaktika pogranichnykh sostoianii v regione Sibiri i Dal'nego Vostoka.

The problem of borderline conditions in the population of Siberia and the Far East is analyzed from the standpoint of a comprehensive multidisciplinary approach. The authors established the indicators, close to the real ones, of the prevalence of borderline disorders, exceeding many times the formal statistic data. Evidence is given of the role of certain personality parameters (rigidity, anxiety) and biological factors (the status of the immune and hormonal systems) in the formation and course of borderline conditions. The clinical studies carried out over time made it possible to specify definite stages in the development of borderline pathology. 3 stages were delineated: initial disorders or reactions; neurotic or neurosis-like conditions; neurotic or pathological developments of the personality. The authors demonstrate imperfection of the existing systems of psychiatric aid in respect to patients with borderline disorders and provide evidence for the necessity of organizing psychiatric services outside dispensary aid. Novel organizational models (the center for borderline conditions, the center for mental health care at industrial enterprises, municipal psychohygienic consultation) developed by the authors are provided as prognosis. These structures made it possible to enhance the efficacy of prevention and treatment of borderline conditions.

[Cytotoxic activity of blood serum in borderline conditions]. / Tsitotoksicheskaia aktivnost' syvorotki krovi pri pogranichnykh sostoianiiakh.

A study was made of cytotoxic activity of blood serum from 118 patients with borderline neuropsychic disorders (neurotic depression, neurosis, psychopathy, pathologic development of the personality on the basis of organic injury to the brain). Material of 114 mentally and somatically healthy donors served as control. Balb mouse thymocytes and organ culture of the rat brain were employed as test objects. ++Anti-thymus activity (ATA) was measured according to the cytotoxic index, whereas neurotoxic activity (NTA) by inhibition of 3H-cholesterol incorporation. The patients and donors groups differed by distribution of persons with high and low values of NTA and ATA. However, according to the mean level of blood serum cytotoxic activity such a difference was revealed only in respect to NTA. The determined parameters are related in a different way to the patient's age and similarly to the disease standing. The intensity of ATA and NTA was different in different nosological subgroups. An interrelationship was established between the clinical and biological dynamics, supporting a possibility of the use of the given tests as predictors of the therapeutic efficacy and the depth of homeostasis derangement.