Neutrophil extracellular traps characterize caseating granulomas.

Tuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO-DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.

Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017-2022.

In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

Treatment outcomes and risk factors for an unsuccessful outcome among patients with highly drug-resistant tuberculosis in Ukraine.

OBJECTIVES: To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome. METHODS: Data from patients with multi-, pre-extensively, or extensively drug-resistant TB were collected prospectively from TB dispensaries in 15 out of 24 Ukrainian oblasts (regions) from 2020 to 2021. Treatment outcomes were evaluated using WHO definitions. Risk factors for an unsuccessful outcome were identified using a multivariable logistic regression model. RESULTS: Among 1748 patients, the overall proportion of successful outcomes was 58% (95% confidence interval [95% CI] 56-60) (n = 1015/1748), ranging from 65% (95% CI: 62-69) (n = 531/814) for multidrug-resistant TB to 54% (95% CI: 49-58) (n = 301/563) for pre-extensively drug-resistant TB and 49% (95% CI: 44-55) (n = 183/371) for extensively drug-resistant TB. Results were similar across oblasts, with few exceptions. The strongest risk factors for an unsuccessful outcome were extensively drug-resistant TB (adjusted OR [aOR] 3.23; 95% CI: 1.88-5.53), total serum protein below 62 g/L in adults and below 57 g/L for children and adolescents (aOR 2.79; 95% CI: 1.93-4.04), psychiatric illness (aOR 2.79; 95% CI: 1.46-5.33), age at TB diagnosis >65 years (aOR 2.50; 95% CI: 1.42-4.42), and alcohol misuse (aOR 2.48; 95% CI: 1.89-3.26). DISCUSSION: The overall proportion of successful outcomes among Ukrainians treated for highly drug-resistant TB was 58%, notably better compared with previous years, but still low for extensively drug-resistant TB. Risk factors for unsuccessful outcomes highlight that addressing socioeconomic factors in TB management is crucial. Efforts in maintaining TB dispensaries during and following the ongoing war are highly warranted.

Chest X-ray as an alternative method of making a preliminary diagnosis in patients with susceptible or drug-resistant pulmonary tuberculosis.

Background: Making a preliminary diagnosis using X-ray methods for the study of resistant and resistant tuberculosis (TB) will help to make a preliminary diagnosis and determine further tactics for the treatment of TB, even with limited resources for microbiological diagnosis of drug resistance of TB. The present study was aimed at identifying chest X-ray differences between susceptible and resistant TB. Methods: A prospective cohort study of data from all consecutive patients with culture-confirmed pulmonary TB admitted during the year to the Kharkiv TB Dispensary No. 1 in Kharkiv, Ukraine. Results: One hundred and sixty-eight patients with lung TB were examined. Patients were divided into two groups: 1st patients with pulmonary TB with resistance of Mycobacterium tuberculosis (MTB) to at least isoniazid and rifampicin (resistant TB) and 2nd pulmonary TB with preserved susceptibility of MTB to anti-TB drugs (susceptible-TB). Patients of 1st group often had lesions in two lobes of the lungs 31.1% and one lung 43.3% versus 15.4% and 2.6% of patients with susceptible TB (P < 0.001). In addition, more than 3 cavities in the lungs 45.5% were significantly more often observed in patients with resistant TB versus 7.9%-the 2nd group (P < 0.001). Smaller cavities were observed in patients with susceptible TB up to 1.99 cm 74% versus 35.2% in 1st group (P < 0.001). We did not observe any significant radiological features depending on the right or left lung, as well as the lobar localization of the TB process. Conclusions: For resistant forms of TB, radiologically, a more widespread TB process in the lungs with the presence of a larger number of cavities and their larger size against a background of a more pronounced clinical picture and mycobacterium excretion than with susceptible TB is characteristic.

Assessing the Cytotoxicity of TiO2-x Nanoparticles with a Different Ti3+(Ti2+)/Ti4+ Ratio.

Titanium dioxide (TiO2) nanoparticles are promising biomedical agents characterized by good biocompatibility. In this study, we explored the cytotoxicity of TiO2-x nanoparticles with a different Ti3+(Ti2+)/Ti4+ ratio and analyzed the efficiency of eryptosis indices as a tool in nanotoxicology. Two types of TiO2-x nanoparticles (NPs) were synthesized by the hydrolysis of titanium alkoxide varying the nitric acid content in the hydrolysis mixture. Transmission electron microscopy (TEM) images show that 1-TiO2-x and 2-TiO2-x NPs are 5 nm in size, whereas X-ray photoelectron spectroscopy (XPS) reveals different Ti3+ (Ti2+)/Ti4+ ratios in the crystal lattices of synthesized NPs. 1-TiO2-x nanoparticles contained 54% Ti4+, 38% Ti3+, and 8% Ti2+, while the relative amount of Ti4+ and Ti3+ in the crystal lattice of 2-TiO2-x nanoparticles was 63% and 37%, respectively. Cell viability and cell motility induced by TiO2-x nanoparticles were investigated on primary fibroblast cultures. Eryptosis modulation by the nanoparticles along with cell death mechanisms was studied on rat erythrocytes. We report that both TiO2-x nanoparticles do not decrease the viability of fibroblasts simultaneously stimulating cell migration. Data from in vitro studies on erythrocytes indicate that TiO2-x nanoparticles trigger eryptosis via ROS- (1-TiO2-x) and Ca2+-mediated mechanisms (both TiO2-x nanoparticles) suggesting that evaluation of eryptosis parameters is a more sensitive nanotoxicological approach for TiO2-x nanoparticles than cultured fibroblast assays. TiO2-x nanoparticles are characterized by low toxicity against fibroblasts, but they induce eryptosis, which is shown to be a promising tool for nanotoxicity screening. The Ti3+ (Ti2+)/Ti4+ ratio at least partly determines the cytotoxicity mechanisms for TiO2-x nanoparticles.

Cytotoxicity of Hybrid Noble Metal-Polymer Composites.

The aim of the present research was to assess the cytotoxicity of gold and silver nanoparticles synthesized into dextran-graft-polyacrylamide (D-PAA) polymer nanocarrier, which were used as a basis for further preparation of multicomponent nanocomposites revealed high efficacy for antitumor therapy. The evaluation of the influence of Me-polymer systems on the viability and metabolic activity of fibroblasts and eryptosis elucidating the mechanisms of the proeryptotic effects has been done in the current research. The nanocomposites investigated in this study did not reduce the survival of fibroblasts even at the highest used concentration. Our findings suggest that hybrid Ag/D-PAA composite activated eryptosis via ROS- and Ca2+-mediated pathways at the low concentration, in contrast to other studied materials. Thus, the cytotoxicity of Ag/D-PAA composite against erythrocytes was more pronounced compared with D-PAA and hybrid Au/polymer composite. Eryptosis is a more sensitive tool for assessing the biocompatibility of nanomaterials compared with fibroblast viability assays.

Antimicrobial Effects of Nanostructured Rare-Earth-Based Orthovanadates.

The search for novel antimicrobial agents is of huge importance. Nanomaterials can come to the rescue in this case. The aim of this study was to assess the cytotoxicity and antimicrobial effects of rare-earth-based orthovanadate nanoparticles. The cytotoxicity against host cells and antimicrobial activity of LaVO4:Eu3+ and GdVO4:Eu3+ nanoparticles were analyzed. Effects of nanomaterials on fibroblasts were assessed by MTT, neutral red uptake and scratch assays. The antimicrobial effects were evaluated by the micro-dilution method estimating the minimum inhibitory concentration (MIC) of nanoparticles against various strains of microorganisms, DNA cleavage and biofilm inhibition. GdVO4:Eu3+ nanoparticles were found to be less toxic against eukaryotic cells compared with LaVO4:Eu3+. Both nanoparticles exhibited antimicrobial activity and the highest MIC values were 64 mg/L for E. hirae, E. faecalis and S. aureus shown by GdVO4:Eu3+ nanoparticles. Nanoparticles demonstrated good DNA cleavage activity and induction of double-strand breaks in supercoiled plasmid DNA even at the lowest concentrations used. Both nanoparticles showed the biofilm inhibition activity against S. aureus at 500 mg/L and reduced the microbial cell viability. Taken the results of host toxicity and antimicrobial activity studies, it can be assumed that GdVO4:Eu3+ nanoparticles are more promising antibacterial agents compared with LaVO4:Eu3+ nanoparticles.

Effectiveness of inhaled hypertonic saline application for sputum induction to improve Mycobacterium tuberculosis identification in patients with pulmonary tuberculosis.

BACKGROUND: This study assessed the effectiveness and diagnostic significance of hypertonic saline sputum induction for improving Mycobacterium tuberculosis (MTB) detection. METHODS: A prospective, randomized, open, two-arm, comparative study on MTB identification effectiveness when using inhaled sodium chloride hypertonic solution was performed in patients diagnosed with pulmonary tuberculosis (TB). Patients were randomly assigned into two groups: group 1 (inhalation group) included patients who inhaled a 7% sodium chloride solution upon admission to the hospital, and group 2 (control group) coughed up their sputum as usual. For both groups, specimens were tested by bacterioscopic, bacteriological, and molecular genetic methods. Diagnostic chest radiography was performed for all participants. RESULTS: In this study, 644 patients (mean age 42.2 years; 151 women, 23.4%) were randomly divided into two groups. Low-quality sputum samples were observed in 7.4% of patients from the inhalation group and 28.8% in the control group (p < 0.001). Acid-fast bacilli (AFB) smear was positive in 65.1% of patients from the inhalation group and 51.3% of controls (p = 0.002). A similar statistically significant situation was observed when culture methods (93.9% inhalation group and 81.9% control group, p < 0.001) and molecular genetic tests (92.2% inhalation group and 79.4% control group, p < 0.001) were used. Thus, active pulmonary TB was not verified microbiologically in 6.1% of patients from the inhalation group and in 18.1% of controls (p < 0.001). CONCLUSIONS: Hypertonic saline sputum induction improves the quality of collected samples. This method may be appropriate to increase the rate of MTB detection in sputum using microscopic, bacteriological, and molecular genetic methods for diagnosing TB on the day of specimen collection. Hypertonic saline sputum induction is suitable for middle- and low-income countries with limited resources and causes no severe adverse effects in TB patients.

UV Light-Activated GdYVO4:Eu3+ Nanoparticles Induce Reactive Oxygen Species Generation in Leukocytes Without Affecting Erythrocytes In Vitro.

Nanoparticles (NPs) have been reported to be promising enhancement agents for radiation therapy. The aim of the study was to assess the cytotoxicity of UV non-treated and UV pretreated GdYVO4:Eu3+ nanoparticles against erythrocytes and leukocytes by detecting eryptosis and reactive oxygen species (ROS) generation. Levels of intracellular ROS in erythrocytes and leukocytes using a ROS-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), as well as eryptosis rate utilizing annexin V staining, following direct exposure to UV-activated and nonactivated NPs were detected by flow cytometry. Blood cells were collected from 9 intact WAG rats. Neither the UV light-untreated GdYVO4:Eu3+ NPs nor the treated ones promoted eryptosis and ROS generation in erythrocytes. Low concentrations of UV light-untreated NPs did not induce oxidative stress in leukocytes, evidenced by unaffected intracellular ROS levels. UV light treatment grants prooxidant properties to NPs, confirmed by NP-induced ROS overproduction in leukocytes. High concentrations of both UV light-treated and untreated NPs altered the redox state of leukocytes. UV light treatment imparts prooxidant properties to GdYVO4:Eu3+ NPs, making them promising radiosensitizing agents in cancer radiation therapy.

Food additive E407a stimulates eryptosis in a dose-dependent manner.

BACKGROUND: Concerns about the biosafety of the common food additive E407a have been raised. It has been demonstrated to induce intestinal inflammation, accompanied by activation of apoptosis, upon oral exposure. Thus, it is of interest to investigate how E407a affects eryptosis, a suicidal cell death mode of red blood cells. OBJECTIVE: To evaluate the effects of semi-refined carrageenan (E407a) on eryptosis. METHODS: Flow cytometry was employed to assess eryptosis in blood exposed to various concentrations of E407a (0 g/L, 1 g/L, 5 g/L, and 10 g/L) during incubation for 24 h by analyzing phosphatidylserine externalization in erythrocytes using annexin V staining and via evaluating reactive oxygen species (ROS) generation using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). In addition, the eryptosis indices mentioned above were determined in rats orally administered E407a at a dose of 140 mg/kg weight for 2 weeks. Confocal scanning laser microscopy was performed to visualize cell membrane scrambling. RESULTS: Oral intake of E407a for 2 weeks by rats was not associated with membrane scrambling in erythrocytes. However, ROS overproduction was observed. Meanwhile, incubation of blood with various concentrations of semi-refined carrageenan resulted in a dose-dependent promotion of eryptosis, evidenced by the enhanced percentage of annexin V-positive erythrocytes and higher mean fluorescence intensity (MFI) values of annexin V-FITC in all erythrocytes. The highest concentration of E407a promotes a statistically significant increase in ROS generation in erythrocytes, suggesting the role of ROS-mediated induction of eryptosis in this case. CONCLUSION: Incubation of blood with the food additive E407a leads to the activation of eryptosis in a dose-dependent manner. ROS-mediated mechanisms are partially responsible for E407a-induced eryptosis.

Neurocysticercosis with symptomatic epilepsy manifestation.

Aim To present a unique case of a 22-year-old male patient with symptomatic epilepsy manifestation on a background of neurocysticercosis (NCC). Methods An Indian student in Kharkiv, who lived in rural parts in India, presented with sudden episodes of seizure followed by severe headaches. Laboratory analyses and neurological status (MRI) were performed. Results Neurological status of the patient revealed nystagmus and difficulty in performing co-ordination tests. General analysis of blood showed raised eosinophil count to 8%. The MRI showed a few small conglomerating peripherally enhancing thick-walled infective granulomas in left frontal lobe with extensive surrounding oedema in the left fronto-parietal lobe. The patient was treated with albendazol, levipil, methylprednisolone and pantoprazole. Clinical symptoms and subsequent MRI showed improvement. Conclusion Neurocysticercosis is often misdiagnosed in the early stages, which leads to adverse outcomes. Although seizures are the most common clinical manifestation, it is a symptom that is not found in majority of the patients. The NCC of adult onset accompanying epileptic seizures is not well studied and a link between the helminthic invasion, epilepsy and psychiatric conditions needs to be established. This disease is potentially eradicable with wellplanned eradication programs targeting all stages of Taenia solium life cycle.

Tourette syndrome or PANDAS-a case report.

Tourette syndrome (TS), a relatively common disorder, has been gaining more attention during the past two decades because of an increased number of reports. Nevertheless, it is still not completely understood. Furthermore, a clinical entity called "pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections" (PANDAS) has been introduced, which describes a tic disorder, accompanied by psychiatric disorders such as obsessive compulsive disorder (OCD), after a streptococcal infection in childhood. We present a case report of a 19-year-old adolescent Ukrainian female, with a history of anxiety disorder and OCD, who, despite TS remission during childhood, presented with new-onset motor and phonic tics after 1 month of severe tonsillitis. Blood and cerebrospinal cultures showed Streptococcus pyogenes, with magnetic resonance imaging revealing hypo-intense changes in the caudate nucleus on both sides. Treatment with clonazepam and fluoxetine, along with behavioral therapy, have improved the severity of her condition. This report presents a case of TS reemergence against the background of immunological reaction or PANDAS with a late adolescent onset.

Treatment effectiveness and outcome in patients with a relapse and newly diagnosed multidrug-resistant pulmonary tuberculosis.

Aim To investigate the treatment effectiveness and outcome in patients with pulmonary tuberculosis relapse and newly diagnosed multidrug resistant pulmonary tuberculosis (MDR-TB). Methods A total of 240 pulmonary MDR-TB patients, including 114 ones with tuberculosis relapse and 126 cases of newly diagnosed pulmonary tuberculosis, were examined. Effectiveness of the basic antimycobacterial therapy course was evaluated based on the time to normalization of tuberculosis clinical manifestation, sputum culture and acid-fast bacilli stain conversion, cavity closure, disappearance of infiltrative and focal changes in the pulmonary tissue. Treatment outcomes were evaluated as cured, treatment completed, treatment failed, died and lost to follow-up according to the World Health Organization guidelines. Results When assessing the treatment effectiveness in patients with MDR-TB, a worse clinical and chest radiograph dynamics was observed in tuberculosis relapse against the background of high parameters of treatment failure (18.4 %) and low cured (34.2 %) compared with newly diagnosed pulmonary tuberculosis (7.1% and 58.7 %, respectively) (p=0.008 and p<0.001, respectively). Conclusion Standard treatment effectiveness in patients with newly diagnosed MDR-TB manifested by faster improvement and stabilization of health, earlier sputum culture and smear conversion, higher frequency of cavity closure and achievement of certain clinical and radiographic improvement against the background of fewer cases of treatment failure and a higher number of cured patients compared with MDR-TB relapse.

Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month.

OBJECTIVE: Immunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct. METHODS: The outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 2:1 ratio: V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo. RESULTS: After one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage. CONCLUSION: Oral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov: NCT01977768).

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection.

BACKGROUND: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. METHODS: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. RESULTS: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). CONCLUSION: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.

Effectiveness of anti-tuberculosis chemotherapy in patients with tuberculosis relapse compared with newly diagnosed patients.

Background: To study the effectiveness of antituberculosis chemotherapy in patients with relapse pulmonary tuberculosis (RTB) compared with patients with the newly diagnosed process. Methods: We examined 285 TB patients, including 126 individuals with RTB (Group 1) and 159 patients with newly diagnosed pulmonary tuberculosis (NDPTB) (Group 2). All patients were diagnosed with infiltrative PTB. Effectiveness of the basic course of antimycobacterial treatment was assessed in accordance with the following data: time required for the normalization of clinical manifestations, smear conversion, cavity healing, disappearance of infiltrative and focal changes in the pulmonary tissue, as well as the final clinical effectiveness of therapy. Results: Disappearance of clinical symptoms was statistically significantly faster in Group 2 compared with RTB patients in 2.25 ± 0.11 and 3.40 ± 0.15 months, respectively (P < 0.001). Sputum culture conversion was observed after 6 months of treatment in 138 (86.79%) patients with NDPTB and 89 (72.22%) patients from Group 1 (P = 0.0023). Closure of cavities and disappearance of infiltrative and focal changes in the lungs occurred within 6 months of chemotherapy only in 55 (43.65%) patients with RTB and 93 (58.49%) patients with NDPTB (P = 0.0133). Conclusions: Standard treatment for patients with NDPTB is considered successful in case of faster health improvement and stabilization, less pronounced rates of toxic adverse reactions to antiTB drugs, faster sputum smear and culture conversion and cavity healing, signs of clinical and radiological convalescence, and the reduced number of large residual changes after the treatment compared with RTB.

Interrelationship of endothelial function parameters in children with bronchial asthma in exacerbation and remission.

INTRODUCTION: In children with asthma, endothelial dysfunction signs are observed, and their extent depends on the severity of the disease. These changes are also present in remission. High level of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) expression causes active adhesion of inflammatory cells and can indicate direct endothelium participation in development and supporting of chronic inflammation. Bronchial asthma (BA) is characterised by airways chronic inflammation. A special role in this inflammatory process formation is played by development of endothelial dysfunction. The aim of the study was to evaluate endothelial state in children with clinically stable and exacerbated asthma. MATERIAL AND METHODS: 91 children with persistent asthma were examined. Among them there were 40 patients with mild persistent (group I), 34 subjects with moderate persistent (group II) and 17 individuals with severe persistent (group III) asthma. 20 healthy children were selected as controls. The serum levels of sVCAM-1 were determined by enzyme-linked immunosorbent assay (ELISA). The ultrasound assessment of endothelium-dependent flow-mediated dilation of the brachial artery (FMD%) has been made. Ultrasonography has been used for investigation of the intima-media thickness (I-M) complex. Data analysis was performed with the Statsoft Statistica Version 8 (Tulsa, OK). RESULTS: The serum levels of sVCAM-1 were significantly increased in the patients with asthma exacerbation (p < 0.001) and remission (p < 0.001), compared with the controls. The index of FMD% was significantly diminished in the patients of I, II, III group with exacerbation (p < 0.001) and stayed lower in the subjects with asthma in remission (p < 0.001), compared with the controls. The thickness of I-M complex was significantly increased in the patients of I, II, III group, compared with the controls (p < 0.001). The endothelium parameter levels: sVCAM-1 (H = 56.11, p = 0.0001), FMD% (H = 43.20, p = 0.0000), the thickness of I-M complex (H = 49.37, p = 0.0000) depend on the severity of the disease. Correlations between the endothelium and pulmonary function parameters were proved (p < 0.05). CONCLUSIONS: Endothelial dysfunction in children with asthma was determined. Dependence of severity of the disease on functional state of the vascular endothelium was proved.

Efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis.

The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase for patients with newly diagnosed pulmonary tuberculosis (pulmonary TB). MATERIALS AND METHODS: The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 years and 68 years. All patient with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in this study. The patients were allocated to two groups. The first (control) group of 46 patients received standard chemotherapy orally. The second (main) group consisted of 46 patients who were prescribed isoniazid, rifampin, ethambutol by i / v transfusion, and pyrazinamide orally as a part of the standard treatment. RESULTS: Symptoms of intoxication in pulmonary TB patients from the second group were eliminated faster (1.42±0.35) of a month than the same symptoms of the group 1-(2.96±0.24) of the months,p < 0.05; disappearance of respiratory symptoms of the group 2-(1.34±0.29) of a month, group 1-(2.65±0.43) of the months,p < 0.05. In the group 2, the bacterioexcretion time was reducing faster and up to 2 months it reached 37(80.43±5.85%) while the time for the control group reached 25(54.35±7.34%),p < 0.05. Destruction healing and healing frequency of destruction cavities up to 4 months amounted to 38(82.61±5.59%) (in control group - 28(60.87±7.20%),p < 0.05) and residual changes were reducing (small changes or absence of even minimal radiological changes were found in 29(63.04 ±7.12%) patients versus 18(39.13±7.20%) of the group 1, and large residual changes accordingly in 17(36.96±7.12%) and 28(60.87±7.20%),p < 0.05. CONCLUSIONS: Thanks to i/v chemotherapy clinical manifestations of the in patients with pulmonary TB were eliminated faster, severe side effects to anti-TB drugs were not noticed, time of bacterial excretion and healing destruction reduced, healing frequency of destruction cavities increased and the residual changes decreased.