Barnase*Barstar-guided two-step targeting approach for drug delivery to tumor cells in vivo.

For precise ligation of a targeting and cytotoxic moiety, the use of Barnase-Barstar pair as a molecular glue is proposed for the first time. Targeting was mediated through the use of a scaffold protein DARPin_9-29 specific for the human epidermal receptor 2 (HER2) antigen that is highly expressed on some types of cancer and Barnase*Barstar native bacterial proteins interacted with each other with Kd 10-14 M. The approach proposed consists of prelabeling a target tumor with hybrid protein DARPin-Barnase prior to administration of cytotoxic component-loaded liposomes that have Barstar covalently attached to their surface. Based on in vivo bioimaging we have proven that DARPin-based Barnase*Barstar-mediated pretargeting possesses precise tumor-targeting capability as well as antitumor activity leading to apparent tumor-growth inhibition of primary tumors and distant metastases in experimental animals. The results obtained indicate that the new system combining DARPin and Barnase*Barstar can be useful both for the drug development and for monitoring the response to treatment in vivo in preclinical studies.

[Tuberculosis hospitals in Russia: requirements, prospects for development].

The results of treatment in patients with tuberculosis are low. Within the first 3-4 months of therapy, lung caverns are closed in 12-26% of patients. The length of tuberculosis inpatient treatment is 79 days, as provided by the state guarantees of rendering free treatment, and the proposals to reduce the number of beds are not substantiated. It is necessary to optimally restructure a bedspace and to bring it into proper sanitary position.

[Prediction of the rate of tuberculosis mortality (calculation methodology)].

Correlation and cross-correlation analyses were used to predict the rate of mortality. The equations of linear and multiple regressions were derived. The indices and factors, which are related and affect the rate of tuberculosis mortality, are defined. Based on the indices, the authors have developed short- and long-term predictions of the rate of mortality. The latter is expected to reduce and stabilize by 2010.

[The results of antituberculous care delivered to the population in Russia in 2003].

The paper presents the results of the activities of tuberculosis-controlling facilities and the general medical network rendering an antituberculous care to the population of Russia in 2003. The epidemic situation in Russian remains to be of strain. There is stabilization or an insignificant improvement of some indices of tuberculosis-controlling work.

[Analysis of risk factors of the occurrence of drug resistance in patients with tuberculosis from civil and penitentiary sectors in the Samara Region].

The true prevalence rates of multidrug-resistant tuberculosis (MDRT) are unknown for most regions of Russia. This study was conducted in the Samara Region that differs from other regions in the rapid spread of HIV infection. The purpose of this study was to determine the primary and acquired resistance of Mycobacterium tuberculosis (MBT) to first-line antituberculous drugs in patients from civil and penitentiary sectors and to reveal risk factors of drug resistance of MBT. Six hundred patients (309 civilians and 291 prisoners who had been bacteriologically diagnosed as having tuberculosis. The authors have established the following:--in new cases, primary drug resistance is as follows: to isoniazid [38.9% (95% CI, 31.3-36.9%)], to rifampicin [25.9% (95% CI, 19.4-33.4%)] and to MDRT [23.0% (95% CI, 16.7-30.3%)];--in prisoners, the primary resistance of MBT was statistically more significant than in civilians;--male sex, in adequate prior or current treatment for tuberculosis for more than 4 weeks, the presence of fibrocavernous tuberculosis and previous prison stay are essential risk factors of the development of resistance of MBT to both any first-line drug and MDRT;--HIV infection is unassociated with resistance.

[Influence of seasonal and environmental factors on the incidence of tuberculosis]. / Vliianie sezonnykh i ékologicheskikh faktorov na zabolevaemost' tuberkulezom.

The seasonal fluctuations of the incidence of respiratory tuberculosis were studied among 3205 new cases aged above 18 years, registered in the Voronezh Region in 1998-2000. The study of the seasonal fluctuations by the dates of filling in notices about a patient with the diagnosis of active tuberculosis established for the first time in his/her life revealed no regularities. A procedure has been proposed for studying the seasonal fluctuation in the development of tuberculosis by the period the early clinical symptoms of the disease occurred. Its highest incidence was registered in winter months. Climatic factors (relative humidity, ambient air temperature, wind velocity) and atmospheric pollution (with dust, nitric oxide, nitric dioxide, carbon monoxide and sulfur dioxide), were found to affect the incidence of tuberculosis. It is advisable to use the findings to determine the time of prophylactic measures.

[Impact of exogenous infection on tuberculosis infection rates in children and adolescents]. / Vliianie ékzogennoi infektsii na infitsirovannost' tuberkulezom detei i podrostkov.

The impact of exogenous infection on the course of an epidemic process was considered. The spread of tuberculosis infection from an ill patient to children and adolescents within a territorial focus was observed. A mapping study allowed the authors to make a goal-oriented search for patients with tuberculosis, as well as primarily infected children and adolescents.

[Tactics of following up patients of tuberculosis facilities]. / Taktika dispansernogo nabliudeniia patsientov protivotuberkuleznykh uchrezhdenii.

The paper proposes a principle of following up patients from tuberculosis facilities, which is based on the patients' need for treatment rather than on the duration of monitoring of cure stability. The proposed scheme of dispensary registration may focus phthisiologists' attention on the patients who really need a follow-up. The use of the scheme in tuberculosis facilities will enhance the efficiency of treatment in patients and reduce the rate of tuberculosis reactivation in patients registered as risk group ones.

[Tuberculosis in Russia in the late 20th century]. / Tuberkulez v Rossii v kontse XX veka.

The present tuberculosis epidemic situation in Russia is marked by an increasing role of exogenous infection. The peak deteriorated epidemic situation was observed in 1993 and 1999. There was a considerable deterioration of the epidemic situation in 1999 due to the economic crisis in August 1998, which caused a drastic fall in living conditions. Trends for an epidemic process changed in the 1990s. Spread of tuberculous infection occurs by the same mechanisms as did in the early 20th century. The official incidence of tuberculosis does not completely reflect actual morbidity (nearly by 15%) due to the fact that patients with tuberculosis have not been detected.

The resurgence of tuberculosis in Russia.

This paper documents and attempts to explain the epidemic spread of tuberculosis (TB) in Russia during the 1990s. After several decades of decline, the notification rate of all new TB cases among permanent residents increased by 7.5% per year from 1991-1999 and the death rate by 11% per year. Growth was quickest from 1993-1995 but increased again after the economic crisis of August 1998. Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case detection and cure rates have fallen in Russia since the mid-1980s; the fall has been accompanied by a higher frequency of severe disease among cases, and higher death and case fatality rates. With a mathematical model describing the deterioration in case finding and cure rates we could replicate the average rate of increase in incidence 1991-1999 but not the precise timing of the observed changes. Other factors that probably helped to shape the observed rise in caseload include enhanced transmission due to the mixing of prison and civilian populations, an increase in susceptibility to disease, and changes in the proportion of cases detected by surveillance. Although our explanation for the resurgence of TB is incomplete, we have identified a set of measures that can be implemented now to cut transmission, incidence and deaths.

Specific features of the spread of tuberculosis in Russia at the end of the 20th century.

This study shows the dynamics of the epidemiological process over the last decade and presents the causes of the deterioration in TB control. Explanations are given for the TB mortality rate increase, the trustworthiness of the data, and the factors influencing its formation. The present-day TB epidemiological situation in Russia is characterized by an increase in exogenous infection. Peaks of epidemiological deterioration were registered in 1993 and 1999. Marked deterioration of the epidemiological situation in 1999 resulted from an economic crisis in August 1998 and a consequent dramatic decrease in the living standards of the population. In the 1990s this trend has changed. TB infection spreads according to trends that are quite similar to those at the beginning of 20th century. The official TB morbidity rate does not reflect the true level of incidence because of undetected TB cases (approx. 10%).