[The diseases of Russia: the medical geographical studies of I. Ya. Lerkhe].

The article analyses the process of establishment of medical knowledge concerning territories of the Russian Empire in XVIII century on the basis of written heritage of the Prussian physician Johann Jacob Lerche (1708-1780). The analysis is focused on forms of actual medical geographical studies practiced by European doctors and Lerche himself, first of all on his meteorological observations. The Lerche's interpretations of local natural and social phenomena in construction of medical characteristics of particular corners of the Empire in manuscript about endemics in Russia and Persia are analyzed. The assumption is proposed that studies of Russia implemented by Lerche are constructed on the analogy of summarizing academic descriptions of naturalists of XVIII century. Thereby, the works of Prussian physician seems to be participated in process of development of language of systematization and ranking of diseases and endowed category of "disease" with function of inherent to region characteristic such as climate, flora and fauna.

FLIM reveals alternative EV-mediated cellular up-take pathways of paclitaxel.

In response to physiological and artificial stimuli, cells generate nano-scale extracellular vesicles (EVs) by encapsulating biomolecules in plasma membrane-derived phospholipid envelopes. These vesicles are released to bodily fluids, hence acting as powerful endogenous mediators in intercellular signaling. EVs provide a compelling alternative for biomarker discovery and targeted drug delivery, but their kinetics and dynamics while interacting with living cells are poorly understood. Here we introduce a novel method, fluorescence lifetime imaging microscopy (FLIM) to investigate these interaction attributes. By FLIM, we show distinct cellular uptake mechanisms of different EV subtypes, exosomes and microvesicles, loaded with anti-cancer agent, paclitaxel. We demonstrate differences in intracellular behavior and drug release profiles of paclitaxel-containing EVs. Exosomes seem to deliver the drug mostly by endocytosis while microvesicles enter the cells by both endocytosis and fusion with cell membrane. This research offers a new real-time method to investigate EV kinetics with living cells, and it is a potential advancement to complement the existing techniques. The findings of this study improve the current knowledge in exploiting EVs as next-generation targeted drug delivery systems.

[Photosensitizing properties of 3,3'-diethylthiacarbocyanine in biological media].

The objective of the study is elucidation of perspectives of 3,3'-diathylcarbocyaine application as a photosensitizer for curing viral infections by photodynamic therapy. Lipid-containing bacteriophage PM-2 of Pseudoalteromonas espejiana was used as a model. The testing was carried out at a special installation modeling photodynamic exposure conditions towards a non-fractionated phage lysate. 3,3'-DECC demonstrated a rapid photo-bleaching when added tothe phage lysate but not to water. The initial rate of PM-2 phage photoinactivation was proportional to the square concentration of the dye in the range of 0.5-9 µmol/L. This confirms a hypothesis that the dimer is the principal photochemically active form of the dye. An improved ability to form dimers was found in the dye in the phage lysate (10-folds better than in the water). The dye formed a stable adduct with the bacteriophage material. This adduct had an extinction maximum at λ(max) = 594 nm and demonstrated the properties of a polymer (sedimentation under a low-speed centrifugation).

[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[The immunogenicity of a cultured inactivated hepatitis A vaccine]. / Immunogennost' kul'tural'noi inaktivirovannoi vaktsiny gepatita A.

A trial of inactivated hepatitis A viral vaccine of heteroploid cell culture origin is described. The vaccine preparation was tested in guinea pigs and tamarins. The animals were immunized intramuscularly four or three times, respectively. The efficacy was judged by induction of anti-HAV antibody persisting for at least 12 months in guinea pigs, and development of immunity to subsequent virus challenge (monkeys only). The challenge dose of HAV was unable to produce any signs of HAV infection in the vaccinated tamarins, although the booster effect was observed in some animals. The study demonstrated that the tested batches of the vaccine were highly immunogenic.

[The purification of tick-borne encephalitis virus preparations of cellular DNA]. / Ochistka preparatov virusa kleshchevogo éntsefalita ot kletochnoi DNK.

According to the WHO requirements, the concentration of cellular DNA in vaccine preparations produced by pooling virus from continuous cell lines is limited to 100 ng/dose. In this study, different methods were used for purification of tick-borne encephalitis virus suspensions grown in continuous cultures of cell line 4647 from cellular DNA. Two approaches are proposed based on treatment with DNAse and promamin sulfate which allow one to reduce cellular DNA concentration in the virus preparation to the acceptable level. Prospects of their use in vaccine production are discussed.