[Lower jaw virtual reposition accuracy research]. / Izuchenie tochnosti virtual'noi repozitsii nizhnei chelyusti.

OBJECTIVE: The aim is to study of the accuracy of the virtual reposition of the mandible (LF) by comparing the virtual and real position of the LF heads, as well as the analysis of factors contributing to the occurrence of errors. MATERIAL AND METHODS: An experimental model of a human skull with a movable LF was made of radiopaque material. The resulting computed tomogram (CT) of the upper and lower jaws and temporomandibular joint (TMJ) was combined with dental scans of dental rows and CT scans and a report on the position of the heads of the LF was obtained. Then the LF was shifted to another position and this position was fixed. Optical bite recorders were obtained using an intraoral scanner. An experimental model with a fixed new position of the LF was placed in a tomograph and repeated CT was obtained. In the program, according to optical registers, a virtual reposition of the LF was carried out. The correspondence of the virtual and real position of the mandibular heads was compared. RESULTS: The absolute difference of glenoid fossa space between the actual and virtual reconstruction was 0.542±0.3354 mm in the anterior joint section (M±Î´, M - average mean, δ - standard deviation); for the upper joint section - 0.309±0.2246 mm; and 0.260±0.1862 mm for the posterior section. The integral indicator of surface coincidence (q) when the virtual and actual position are directly compared was 0.296±0.1254 (s.u.). CONCLUSION: The total margin of error depends on the following factors: repeated scanning error (teeth arches and bite scans), repeated CBCT error, a combination of scan and CBCT error, a combination of teeth arch scan and bite scan error, error of TMJ separation. The latter two factors were the most significant.

Decrease in Bcl-2 Protein Level during the Development of Lewis Carcinosarcome.

We studied the development of Lewis carcinoma and possible antitumor effect of preliminary administered antioxidant anphen. The tumor was intramuscularly transplanted to C57Bl×DBA mice (7×106 cells per mouse). According to immunoblotting results, the content of anti-apoptotic Bcl-2 protein steadily decreased starting from post-transplantation day 11. In few days, its content decreased by 15-20% and soon the animals died. After administration of anphen, the content of Bcl-2 decreased more rapidly than in the control. Atomic force microscopy revealed a decrease in the mean volume of erythrocytes and then increase in this parameter at the terminal stage of tumor growth. These findings suggest that anphen does not affect the tumor growth rate and mouse lifespan, but enhances apoptosis of blood cells of animals with Lewis carcinoma at the terminal stages of tumor growth.

Effect of Promising Antitumor Phenolic Antioxidant Anphen Sodium on the BCL-2 Family Proteins.

The proapoptotic effect of anphen (the effect on the level of the antiapoptotic protein Bcl-2) was investigated by immunoblotting. Incubation of Lewis carcinoma cell suspension with anphen at a concentration of 10-6 M for 0-3 h caused a 80% reduction in the level of the Bcl-2 protein and its homodimer. In vivo, when administered for 4 days to outbred mice, anphen (10-4 M) induced a decrease in the level of the Bcl-2 homodimer in the spleen cells by 20% and an increase in the content of the Bad protein (apoptosis activator) and the Bcl-XL protein. The antitumor effect of anphen may be due to blocking the hydrophobic pocket of the Bcl-2 protein.

Performance of Cepheid ® Xpert MTB/RIF ® and TB-Biochip ® MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis.

The purpose of this study was to assess the performance of Cepheid® Xpert MTB/RIF® ("Xpert") and TB-Biochip® MDR ("TB-Biochip"). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein-Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube® (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0-98.3 %] than direct (59.6 %, 95 % CI, 50.2-68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7-91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4-87.5 %); the specificity was 86.0 % (95 % CI, 78.9-91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5-99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8-99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0-99.5 %); the specificity was 78.1 % (95 % CI, 61.5-89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2-100 %) of RIF-R, 94.7 % (95 % CI, 76.7-99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4-99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1-94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods.

[Effect of oregano essential oil on the engraftment and development of Lewis carcinoma in F1 DBA C57 black hybrid mice].

The effect of a low uptake dose of oregano essential oil with drinking water for three months (Origanum vulgare L.) on the degree of Lewis carcinoma engraftment and some parameters of oxidative stress has been studied in vivo using F1 DBA C57 Black hybrid mice. Oregano essential oil has been established to possess an anticancer activity. The degree of tumor engraftment decreased by 1.8 times, its size decreased by 1.5 times, and the development of tumor was significantly suppressed in sick mice under the effect of oregano essential oil. It was found that the uptake of essential oil did not affect the intensity of lipid peroxidation in the brain of mice and resulted in a significantly (by 36%) decreased content of secondary lipid oxidation products in the liver as shown in a reaction with thiobarbituric acid as compared to control subjects. The activity of antioxidant enzymes was found to increase after three months of essential oil uptake (by 1.5-3 times) as compared to the control group. This effect of essential oil supports the presence of bioantioxidant properties in this essential oil.

[Selective effects of pulmonary surfactant on various subpopulations of alveolar macrophages in the model of experimental tuberculosis].

Pulmonary surfactant is necessary component for maintenance of high level of phagocytic activity of alveolar macrophages. Tuberculosis inflammation reduces the production of surfactant by type II cells and phagocytic activity of alveolar macrophages. The effects of exogenous pulmonary surfactant on the ultrastructural changes of various subpopulations of alveolar macrophages were studied by TEM-method. For investigations the bronchial alveolar lavage fluid from guinea pigs infected of M. tuberculosis and treated by isoniatid or isoniazid + exogenous pulmonary surfactant were used. It was shown that isoniazid + exogenous pulmonary surfactant normalizes the heterogeneous population of alveolar macrophages providing stimulating effects on their maturation and phagocytic activity more effectively than isoniazid therapy.

[Prevention of tuberculosis: current approaches to development of vaccines].

This review is focused on recent advances in development of new vaccines for the prevention of tuberculosis. The main reasons for lack of BCG vaccine efficacy in different populations and geographic regions are presented. Design of new vaccines based on live modified strains of Mycobacterium bovis BCG, attenuated strains of Mycobacterium tuberculosis, recombinant proteins and viral vectors is considered in the specific examples. The usage of the heterologous "prime-boost" vaccination strategy against tuberculosis is discussed.

3D structure reconstruction of nanoengineered polymeric capsules using Coherent X-Ray diffraction imaging.

Nanoengineered polymeric capsules (NPCs) are smart objects that can be filled in with some desired chemical substance. They are considered among the most versatile tools in biology, pharmacy, medicine etc. Most often they have been used as containers for drug delivery. Main tools for studying their structure are electron (SEM, TEM) and fluorescence microscopies. In the case of electron microscopies, the main peculiarity was connected to the necessity of dried samples usage. In the case of fluorescence microscopy, the possible resolution is restricted by diffraction limits. The natural environment of the NPCs is liquid medium. In this paper we have developed a method of NPCs' structure investigation in liquid medium using coherent X-ray diffraction imaging (CXDI). The main points of this article are summarized as:•The procedure of NPCs' synthesis using layer-by-layer technique including gold nanoparticles;•Coherent X-ray diffraction imaging of the samples in liquid medium;•Imaging of objects without freezing of the sample.

[Monitoring detection and treatment of new patients with pulmonary tuberculosis].

We estimated results of detection and treatment of TB patients registered in 2006 in 15 regions of RF under supervision of the Central Research Institute of Tuberculosis. The fraction of sputum positive patients increased in comparison with 2005. It ranged from 77.1% in Orel region to 35.2% in Astrakhan region. The primary MDR rate varied significantly from 2.5% in the Republic of Mordovia to 14.7% in Mary El (estimated level 5%). The frequency of efficient chemotherapy (evaluated from sputum microscopy data) increased in 8 regions and decreased in 7 ones. The efficiency varied from 69.0 to 81.1% in 9 regions (recommended level for 2007 68.5%). It amounted to 68.5% or higher (based on sputum culturing data) in Republics of Kalmykia and Tatarstan, Nizhny Novgorod, Saratov and Ul'yanovsk regions. TB mortality rate in 2006 exceeded the acceptable level of 2.5% in 13 regions and the frequency of refusals to continue chemotherapy was higher than 5% recommended for 2010 by the Global Fund Target Project in 10 regions. The efficiency of treatment in sputum-positive patients was frequently evaluated by X-ray in 3 regions with poorly organized microbiological services. TB treatment efficiency estimated from cavity closure was higher than 60% in 10 regions; it the remaining ones it varied from 36,3% (Nizhny Novgorod) to 52.2% (Vladimir). The system of evaluation being tested permits to accurately register new TB patients, objectively estimate effectiveness of their treatment, and reveal causes of its failure. Also, it makes possible corrections of therapeutic strategy on a trimestrial basis instead of postponing them till the end of the year. Introduction of cohort analysis combined with supervision of responsibility regions by specialists of relevant research institutions would increase efficiency of TB control in each subject of Russian Federation. Supervisory management appears to be an efficacious tool for monitoring implementation of the TB control Program.

[The effect of volatile antioxidants of plant origin on leukemogenesis in mice].

The effect of savory essential oil added with drinking water (150 ng/ml) or with feed (2.5 microg/g) on the lifetime of AKR mice and the parameters of oxidative stress in animal blood were investigated. It was found for the first time that long-term administration of an essential oil in low doses increased the average lifetime of mice by 20-35% and was accompanied by a decrease in the hemolysis level and the content of lipid peroxidation products in erythrocytes of mice, as well as alteration in the structural state of their membranes and stabilization of polyunsaturated fatty acids level in mice liver cells.

[Comparison of radionuclide studies with pleural morphological changes in patients with tuberculosis pleurisy].

Forty-seven patients with pleurisy of tuberculous etiology underwent a radionuclide study using the reagent 99mTc-labeled technefit, the result of which was compared with the morphological changes in the pleural biopsy or resection specimens. First-degree pleural resorptive dysfunction (PRD) was ascertained in 27.6% of the patients. Morphologically, there were signs of acute edema of all pleural layers in both the area of inflammation and the proximal portions with reduced vessels in the microcirculatory bed (MCB). These patients had medical treatment. 59.6% of patients had second-degree PRD--circumscribed caseous foci and granulomas were morphologically found in the presence of progressive fibrosis with a small number of vessels in the MCB. 12.8% of patients had third-degree PRD--massive pleural fibrosis with a significant reduction in MCB vessels and lymph capillaries. Active tuberculous inflammation remained mainly in the deep layers of the pleura. Surgical treatment was performed in patients with second-third degree PRD. Thus, comparison of the results of a radionuclide study with morphological changes in the tuberculosis-afflicted pleura made it possible to establish the degree of pleural MCB impairments, to characterize the activity of a pathological process, and to define objectively treatment policy.

[Psychoemotional changes in patients with pulmonary tuberculosis during therapy using psychological and neuropsychological methods].

Therapy for pulmonary tuberculosis in patients is complicated by their negative psychoemotional state frequently deteriorated by long inpatient stay. Enhancing the efficiency of rehabilitative measures in phthisiology requires active optimization of the patients' mental state. This problem can be solved by a package of correction measures involving psychological correction with reflex therapeutic normalization of the functional state of the cortical regions of the central nervous system in patients with pulmonary tuberculosis. One hundred tuberculosis patients with decompensated mind, including 60 with OG and 40 with KG, were examined. A noticeable psychoemotional improvement was reliably detected 5 months after complex correction psychological and neuropsychological accompaniments of standard chemotherapy in the OG study.

[Up-to-date technologies in preoperative preparation and postoperative period in patients with progressive destructive pulmonary tuberculosis].

The impact of complex pathogenetic treatment involving the latest advances of science and technology in the correction of pulmonary surfactant system (PSS) disorders, extracorporeal therapy and immunomodulation on the enhancement of efficiency of surgical treatment in patients with progressive destructive tuberculosis of the lung. The results of examinations and treatment were studied in 199 patients with progressive and complicated pulmonary tuberculosis. According to the used treatment, the patients were divided into 2 groups: a study group (n = 102) and a control one (n = 97). In the pre- and postoperative periods, the study group patients received complex pathogenetic therapy by the developed algorithm: for pharmacological activation of PSS, nebulizer aerosol therapy with lasolvan (ambroxol) was first used in various modifications by the developed algorithms. The efficiency of preoperative preparation in the study group patients in accordance with the applied methods of pathogenetic therapy indicated that the best results were achieved in the context of stabilization of a specific process, compensation of complications and comorbidity in the patients who underwent modified drug-induced PSS activation with small-volume plasmapheresis and leukinferon (LI) in 93.3% and drug-induced PSS activation with small-volume medical plasmapheresis (MI) in 81.4%. Overall, comprehensive preoperative preparation involving correction of homeostatic disorders by the developed algorithm proved to be 30.9% more effective (81.4%) than the conventional preoperative preparation in the controls (50.5%). Analysis of the results of surgical treatment depending on the methods of pathogenetic therapy used in the pre- and postoperative period showed that the efficiency of surgical treatment was observed in 25 (80%) patients receiving nebulizer aerosol therapy and MP, in 20 (86.9%) who had nebulizer aerosol therapy + MP and in only 8 (65%) treated with nebulizer aerosol therapy.

[Monitoring of the detection of new pulmonary tuberculosis cases and the efficiency of their treatment in the area supervised by the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences].

The results of the detection and treatment of new pulmonary tuberculosis cases in 2006 were assessed in 15 subjects of the Russian Federation, supervised by the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences. As compared with 2005, in 2006 the proportion of bacteria-discharging individuals increased among the new cases of pulmonary tuberculosis and ranged from 77.1% in the Oryol Region to 35.2% in the Astrakhan Region. The frequency of multidrug-resistant MBT among the new cases of pulmonary tuberculosis (the expected frequency was 5%) showed a wide scatter and varied from 0.7% in the Republic of Ingushetia to 14.7% in that of Mariy El. The higher and lower percentages of patients receiving an effective course of chemotherapy, as shown by microscopy, were noted in 8 and 7 regions, respectively. Their scatter was 42.4% in the Nizhni Novgorod Region to 81.1% in the Republic of Mordovia. The efficiency of treatment, as evidenced by sputum culture, varied from 46.3% in the Nizhni Novgorod Region to 79.0% in the Republic of Mordovia. More than 3% of those who died from tuberculosis were recorded in 10 regions and more than 5% of those who discontinued a course of chemotherapy before the appointed time were notified in 8 regions. The cavity decay closure rate ranged from 36.3% in the Nizhni Novgorod Region to 52.2% in the Vladimir Region. Quarterly monitoring of the detection and treatment allows a precise registration of identified tuberculosis patients, objective assessment of the results of treatment, elucidation of reasons for ineffective chemotherapy, and corrections of a treatment process.

[The clinical and morphological features of the course of tuberculosis in HIV infection].

The development of an acutely progressing process of varying extent to the point of total damage to both lungs is typical of a patient with tuberculosis concurrent with HIV infection due to progressive immunodeficiency. There is an apparent need for dividing patients with comorbidity into 2 groups: (1) HIV/TB, in patients HIV infection is a primary disease; (2) TB/HIV, in whom tuberculosis is accordingly primary. These groups differ in clinical manifestations, forms of tuberculosis, and pathomorphological changes. Group 1 patients are mostly typified by the primary forms of tuberculosis with involvement of lymph nodes of all groups and by miliary processes at the sites of multiple organs (the lung, abdomen, and central nervous system). Most patients from Group 1 are observed to have fever, progressive intoxication, and morphologically necrotic foci without signs of differentiation and in the absence of typical granulomas. Multiple drug resistance is noted in more than 20% of the patients; in these patients, the efficiency of an intensive therapy phase in arresting bacterial discharge is 26.9%. In Group 2 patients, comorbidity takes a less acute course, pulmonary symptoms are less marked; there is a preponderance of infiltrative, disseminated, firocavernous pulmonary tuberculosis, and caseous pneumonia. In this group, the signs of a prior tuberculous process with phenomena of a slight or moderate productive reaction and with resolution elements are morphologically detectable. In late-stage HIV infection--AIDS, the patients from both groups develop a generalized tuerculous process. Both patient groups are typified by the severe progressive course with identical clinical and pathomorphological manifestations, which results in death.

[Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis].

The study undertaken 3 years ago examined the effect of systemic transplantation of autologous mesenchymal stem cells (MSC) in the complex therapy of 27 patients with pulmonary tuberculosis, including 15 patients with multidrug-resistant pulmonary tuberculosis and 12 with extensive drug resistance of Mycobacterium tuberculosis. All the patients were bacteria-discharging persons with disseminated destructive processes in lung tissue, most (n=17) of them had chronic fibrocavernous tuberculosis. In all the patients, previous long specific antituberculous treatment was ineffective or inadequately effective. After systemic MSC transplantation, 16 patients were followed up for 1.5-2 years or more and the remaining 11 patients for at least 6 months. After MSC administration, a positive clinical effect was observed in all 27 cases; bacterial discharge stopped in 20 patients after 3-4 months; resolution of sustained lung tissue cavities further occurred in 11 patients. At present, a persistent remission of a tuberculous process may be stated in 9 of the 16 patients in whom MSCs were transplanted 1.5-2 years, significant positive bacteriological and morphological changes are observed in 6 patients. Thus, inclusion of transplantation of the autologous MSCs propagated in the culture into a course of antituberculous therapy may be a promising procedure for enhancing the efficiency of therapy in patients with resistant forms of pulmonary tuberculosis.

[Pathomorphological changes in the lung in tuberculosis patients died from HIV infection at the stage of AIDS].

The authors revealed the typical morphological changes of lung tuberculous lesion in HIV infection at the stage of AIDS: these included alterative changes without typical tuberculosis granulomas; a well-defined exsudative inflammatory component with a predominance of leukocytic infiltration and a drastically decrease of and, occasionally, a complete disappearance of macrophages and lymphocytes; formation of pyonecrotic foci; the focal monomorphic pattern illustrating the loss of the signs of process indulation. These signs suggest the specific features of immunity and the course of specific inflammation as immediate hypersensitivity with the acutest progression of tuberculosis.

[Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid (phenosan) on the development of malignant neoplasms].

The effect of different doses of synthetic antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl)propionic acid (phenosan) on the development of spontaneous leukemia in AKR mice was studied. The drug efficiency was determined from the survival curves, animal life spans, and the incidence of leukemia. Phenosan exhibited a pronounced antitumor activity at therapeutic (10(-4) mol/kg, 4 administrations) and ultra-low (10(-14) mol/kg, 4 administrations) doses. The dose of 10(-4) mol/kg proved most efficient to increase the life span of the shortlived subpopulation, while the dose of 10(-14) mol/kg increased the life span of the long-lived subpopulation. The ultra-low dose of the drug seems promising as a prophylactic agent.

[Experience with small-volume plasmapheresis used in the correction of hemostatic disorders in patients with progressive destructive pulmonary tuberculosis].

Pulmonary tuberculosis may result from a complex of the phenomena predisposing to impaired blood coagulation. The purpose of the investigation was to study the efficiency of small-volume plasmapheresis in the correction of hemostatic disorders in patients with progressive destructive pulmonary tuberculosis. The results of examination and treatment were analyzed in 112 patients aged 18 to 65 years who had progressive destructive pulmonary tuberculosis treated at the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, in 1994 to 2004. The patients were divided into groups: Group 1 (basic)--43 subjects receiving the standard therapy supplemented by 4 small-volume plasmapheresis sessions every 2 days and comparison groups: 2A--36 patients receiving 2 plasmapheresis sessions at a week interval and 2B--33 patients being on the standard therapy alone. In the presence of endogenous intoxication, the patients with disseminated and complicated fibrocavernous tuberculosis were ascertained to develop blood coagulative disorders typical of grades 1-2 chronic disseminated intravascular coagulation (DIC). The use of small-volume plasmapheresis in combination with antiaggregatory and anticoagulant therapy in patients with disseminated and complicated fibrocavernous pulmonary tuberculosis had a beneficial effect on the blood aggregation controlling system positive impact, prevented DIC progression, promoted improvement of blood rheological properties. With the standard therapy (including double plasmapheresis at a week interval), positive hemostatic changes were absent throughout the preoperative period.