[International approaches to the regulation of cell therapy products].

This article is a review of the main methods and approaches used in regulation of cell therapy products in the United States of America, Canada, European Union, Australia, Japan and South Korea. Intensive developments ofscientific and technological aspects in stem cell and tissue engineering have led to the wide use of human cells and tissues for the treatment of various diseases and injuries of organs and tissues. Drug regulatory agencies of different countries are working on implementation of a risk-based legal framework with some common features. In many countries there is a multilevel control system that assures quality and safety of used cell products. Competent authorities establish strict requirements both to safety of the products and to the implemented standards of good laboratory, manufacturing, clinical and tissue practices.

[Regulatory science: modern trends in science and education for pharmaceutical products].

This article reviews modern trends in development of new instruments, standards and approaches to drugs safety, efficacy and quality assessment in USA and EU that can be called by unique term--"regulatory science" which is a new concept for Russian Federation. New education programs (curricula) developed by USA and EU universities within last 3 years are reviewed. These programs were designed in order to build workforce capable to utilize science approach for drug regulation. The principal mechanisms for financing research in regulatory science used by Food and Drug Administration are analyzed. There are no such science and relevant researches in Russian Federation despite the high demand as well as needs for the system for higher education and life-long learning education of specialists for regulatory affairs (or compliance).

[Risk control strategy in the sphere of circulation of pharmaceuticals].

The article deals with classification of pharmaceutical risks and methodical approaches to their control in the system of governmental regulation of pharmaceuticals. According to the origin of risks and possibilities of their control, the authors distinguish "outer risks", not controlled by a consumer, and "inner risks", whose probability can be lowered by a consumer. Among the "outer risks" there are systematic risks, expressed by probability of adverse effects, and diversified risks, associated with pharmaceutical quality, practice of their administration and application, and partly--with insufficient knowledge of them. As an example the authors analyze risks associated with pharmaceutical quality of medicaments withdrawn from drug-stores by Ministry of Health of Russian Federation. In order to control such risks, the authors offer classification of pharmaceuticals according to the degree of controllability of manufacturing process, the ways of administration of a pharmaceutical (pharmaceutical dosage form), the severity of harm that can be caused to a consumer due to a defect not revealed by the manufacturer, and the degree of risk for population health. The authors reckon that the methodical approaches to pharmaceutical risk control may be used in evaluation of existent mechanism of providing safety for a pharmaceutical consumer, as well as in development of State strategy of increasing pharmaceutical safety.

Probiotics and mechanisms of their curative action.

Information about probiotics used for the correction of resident normal colon microflora and mechanism of their positive therapeutic actions are presented. Probiotics are drugs containing live microbes or substances of microbial origin that, when introduced by natural methods, are expected to confer beneficial physiologic, biochemical and immune effects to the host through the stabilization and optimization of functions of normal microflora. Probiotics containing the Bifidobacterium, Lactobacillus, Escherichia, Enterococcus, Asporogenic aerobe Bacillus and Saccharomyces boulardii microorganisms are characterized.

[Platelet activating factor and pulmonary tuberculosis]. / Faktor aktivatsii trombotsitov i tuberkulez legkikh.

The content of platelet-activating factor (PAF) in plasma, blood, native neutrophils, in the same neutrophils after their incubation with a killed BGC culture and in the incubation medium was measured in 74 patients with various types of active pulmonary tuberculosis. Twelve healthy volunteers formed a control group. PAF was measured by the rabbit platelet aggregation technique. Higher plasma PAF levels were found in half the patients. The highest plasma PAF concentration was observed in the newly revealed patients, in cases with forming cavities in the lung tissue, in those discharged a lot of sputum Mycobacterium tuberculosis, and in those with lymphopenia. PAF content in the native neutrophils of patients was 10 times as high as that in healthy persons. Incubation with the killed BCG culture had no influence on PAF content in the control neutrophils, but greatly increased individual differences in patients. The concentration of PAF in the incubation media of stimulated neutrophils from tuberculosis patients was 3 times higher than in the controls.

[Generation of platelet activating factor by neutrophils in patients with pulmonary tuberculosis]. / Generatsiia faktora aktivatsii trombotsitov neitrofilami krovi u bol'nykh tuberkulezom legkikh.

PAF levels in native blood neutrophils before and after 1-hour incubation with killed BCG culture and in relevant incubation medium were measured in 44 patients with active pulmonary tuberculosis according to rabbit platelet aggregation. A control group consisted of 12 healthy volunteers. Neutrophil PAF concentrations in the patients were 6 times higher than those in the controls and caused a rise in plasma PAF levels. Intracellular PAF content was related to the process characteristics (new-onset tuberculosis, exacerbation, recurrence), intoxication, hemogram shifts and immune status of the patient. In vitro experiments showed that in response to a specific phagocytosis object, generation of PAF in neutrophils and its release into the intercellular space depend on initial PAF levels in native cells. In normal and moderately elevated PAF in native neutrophils contact with killed BCG culture entailed its intracellular content increase, while in initially high intracellular PAF additional stimulation induced primarily its release.