[Ecology and epidemiology of tick-borne infections in the Primorsky Krai].

Interrelation of parasitological and epidemiological estimations of potential danger of different territories Primorsky Krai concerning presence of natural foci of tick-borne diseases is discussed. Comparative analysis of long-term dynamics of the tick-borne diseases' sickness rate in comparison with long-term dynamics of the vector ticks' abundance has been carried out.

High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors.

The purpose of the study was to evaluate the feasibility and safety of two cycles of high-dose chemotherapy (HDT) followed by autologous hematopoietic SCT (HSCT) in patients with poor prognosis Ewing family of tumors (EFT). Twenty patients with primary metastatic bulky disease or recurrent EFT were enrolled to a treatment protocol with two cycles of HDT and HSCT. Patients tolerated well the first (n=20) and second (n=13) cycles, with limited and predictable toxicities. Only one (5%) TRM occurred during the second cycle. Myeloid engraftment occurred at the median of 11 days after both cycles. At 3 years, the overall and EFS were 45% (confidence interval; CI 0.22, 0.69) and 47% (CI 0.25, 0.70), respectively, for the entire group and 58% (CI 0.30, 0.86) for patients who completed two cycles. Dose intensification with two cycles of HDT and HSCT is feasible and safe, with low and acceptable treatment-related morbidity and mortality. Adding a second course of therapy does not impair engraftment. However, only 65% of the patients were able to proceed to the second cycle. Further studies are required to define the optimal mode of delivery of HDT and HSCT in treatment of advanced EFT.

[Nosogeographical estimation of the territory of Primorsky Krai based on the analysis of spatial and temporal structure of the incidence of infectious diseases].

Nosogeographic estimation of the territory of Primorsky Krai has been carried out on the base of the long-term data on spatial distribution of the incidence of infectious diseases. Analysis of the complex maps of the zoning allow us to say, that the territory of the region is rather clearly differentiated by the groups of infections.

[Spatial and temporal structure of the infectious diseases incidence in the population of the south of the Russian Far East: system approach].

New conception of the anthropo-parasitic system has been elaborated. Spatial and temporal structure of the infections diseases incidence in the Primorye Territory has been analysed on the base of this conception.

[Modern problems in the study of tick-born encephalitis natural foci].

A new conception of natural focus as anthropo-parasitic system is given by an example of tick-born encephalitis. Problems of natural foci classification and zoning of focal territories, as well as patterns of ecological relations in these systems, are considered. Causes and factors affected expansion of the infection are analyses.

[Possibilities of factor prognosis of the tick born encephalitis in the Primor'e region]. / Vozmozhnosti faktornogo prognozirovaniia zabolevaemosti kleshchevym éntsefalitom v Primorskom krae.

A technique of temporal factor prognosis of the tick born encephalitis infection during in real time has been elaborated and tested. High adequacy of prognosis for certain regions of the Maritime territory with the tick borne encephalitis foci has been achieved. This approach has a methodological and applied importance and may be used in medico-ecological and epidemiological investigations.

[Some aspects and perspectives of factor prognosis for the epidemic manifestation of tick-borne encephalitis based on a multidimensional analysis of temporal rows]. / Nekotorye aspekty i perspektivy faktornogo prognozirovaniia épidemicheskogo proiavleniia ochagov kleshchevogo éntsefalita na osnove mnogomernogo analiza vremennykh riadov.

A method of factor temporal prognosis for the epidemic manifestation of the tick-borne encephalitis foci has been elaborated, based on recognized critical levels of infection. High reliability of possible prognoses and obvious perspectives of the proposed method are noted.

[Some aspects of the resistance of natural foci of zoonosis infections with an example of the tick-borne encephalitis]. / Nekotorye aspekty ustoichivosti prirodnykh ochagov zoonoznykh infektsii na primere kleshchevogo éntsefalita.

Epidermiological material reflecting some spatio-temporal aspects of the natural foci of tick-born encephalitis resistance has been analysed. The investigation carried out can used as a base for elaboration and realisation of factor prognoses concerning natural foci of zoonosis infection.

DRV liposomal bupivacaine: preparation, characterization, and in vivo evaluation in mice.

PURPOSE: To evaluate the dehydration-rehydration technique to prepare a formulation of liposomal bupivacaine, and to assess its analgesic efficacy. METHODS: Bupivacaine hydrochloride (BUP) was encapsulated into dehydration-rehydration vesicles (DRV) of varying phospholipid (PL) compositions. Two bilayer-forming phospholipids were used, the "fluid" dimyristoyl-phosphatidylcholine and the "solid" distearoyl-phosphatidylcholine (DSPC), with 20 or 40 mol% cholesterol, in the presence of bupivacaine at a 1.28 or 0.64 BUP/PL mole ratio. After rehydration, drug/lipid ratios were determined. The formulation with the highest drug/lipid ratio (DSPC/cholesterol in an 8:2 mole ratio prepared in the presence of bupivacaine in a 1.28 BUP/PL mole ratio) was adjusted to a final bupivacaine concentration of 3.5% or 0.5%. The duration of skin analgesia after subcutaneous injection in mice produced by these formulations was compared with the conventional administration of a plain 0.5% solution of BUP. In addition, the concentration of residual bupivacaine at the injection site was followed for 96 h. RESULTS: The relatively low organic solvent/aqueous phase and membrane/aqueous phase partition coefficients, together with liposomal trapped volume and BUP/PL mole ratio, indicated that most of the drug was encapsulated in the intraliposome aqueous phase of the DRV. The DSPC/cholesterol 8:2 mole ratio had the best drug encapsulation (BUP/PL = 0.36). Compared to plain BUP, these BUP-DRV produced significant prolongation of analgesia, which is explained by longer residence time of the drug at the site of injection. CONCLUSIONS: Bupivacaine-DRV may have a role in achieving safe, effective, and prolonged analgesia in humans.

[Functional organization of natural tick-borne encephalitis foci and prognosis of their epidemic manifestation: analysis of one-dimensional temporal series of infection]. / O funktsional'noi organizatsii prirodnykh ochagov kleshchevogo éntsefalita i prognoze ikh épidemicheskogo proiavleniia: analiz odnomernykh vremennykh riadov zabolevaemosti.

Temporal extrapolation prognosis of tick-borne encephalitis diseases in the Primorye territory and its certain regions is made by means of autoregression models. The results obtained shows good prospects of used methods and models.

[A medico-geographical assessment of the land area of the Maritime Territory relative to tick-borne encephalitis with some remarks on the structural organization of the foci of said infection]. / Mediko-geograficheskaia otsenka territorii Primorskogo kraia otnositel'no kleshchevogo éntsefalita s nekotorymi zamechaniiami o strukturnoi organizatsii ochagov dannoi infektsii.

A division of the Primorskiy Kray into districts in relation to the tick-borne encephalitis was based on three criteria: long-term dynamics of infection, chorological structure of ixodid tick populations and probability of this or that clinical form of infection.

Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count.

IL-7 is produced by stromal cells and is the major lympho- and thymopoietic cytokine. IL-7 induces proliferation and differentiation of immature thymocytes, and protects thymocytes from apoptosis by induction of bcl-2 expression. The regulation of IL-7 production is poorly characterized, although down-regulation by transforming growth factor-beta (TGF-beta) has been described. We measured the serum levels of IL-7 before and after bone marrow transplant (BMT) in 32 children undergoing BMT for genetic diseases (severe combined immune deficiency (SCID) and thalassemia), aplastic anemia, and acute lymphoblastic and non-lymphoblastic leukemia (ALL and ANLL). Prior to BMT, the highest IL-7 levels were observed in patients with SCID and ALL, i.e. those patients with genetic or acquired lymphopenia. Patients with thalassemia and ANLL had normal levels of IL-7. Over the 8 weeks following BMT, the IL-7 levels of patients with SCID and ALL fell as the absolute lymphocyte count (ALC) increased. No detectable change in IL-7 levels was observed in the patients with thalassemia and ANLL. Levels of IL-7 were highest in the young infants with SCID compared to the age-matched controls. Together, the data demonstrate that serum levels of IL-7 in lymphopenic patients are inversely related to patient age and the absolute lymphocyte count (ALC). The inverse relationship to ALC suggests that there is either direct regulation of stromal production or more likely, binding of secreted IL-7 to lymphocytes expressing IL-7 receptors.

[Methodological aspects in the study of the natural foci of zoonoses]. / Nekotorye metodologicheskie aspekty izucheniia prirodnykh ochagov zoonozov.

Conceptions of different authors on the natural focus of zoonosis infections are analysed and an improved definition of this phenomenon is proposed. The natural focus of disease is the antropoecosystem of certain hierarchic level (biosocial system), where the existence and appearance of the infection agent is supported and the disease is realized in people at certain infection rate.

[An analysis of geographical differences in the appearance of tick-borne encephalitis]. / Analiz geograficheskikh razlichii proiavleniia kleshchevogo éntsefalita.

Reasons of differences in clinical forms of tick-borne encephalitis within certain regions and throughout all area are analysed. It is supposed that the epidemic potential of natural focus depends upon temperature conditions during the winter period.

[The structure and functioning of tick-borne encephalitis foci in the southern Far East]. / Nekotorye aspekty izucheniia struktury i funktsionirovaniia ochagov kleshchevogo éntsefalita iuga Dal'nego Vostoka.

Based on a statistic data on cases of different clinical forms of the tick-born encephalitides in the Russian Far East during 35 years passed it is stated that ecological relations in natural foci of this infection have clear and stable spatio-temporal specific features and hierarchic structure. The epidemic potential of the tick-born encephalitis foci is determined in a great degree by conditions of a cold period of year.

Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7.

Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen-specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

Targeted delivery of doxorubicin via sterically stabilized immunoliposomes: pharmacokinetics and biodistribution in tumor-bearing mice.

PURPOSE: To evaluate benefits in tumor localization, availability, and noncancerous organ distribution of doxorubicin (DOX) delivered via small (< or = 120 nm) sterically stabilized immunoliposomes targeted against a tumor-associated antigen in fibrosarcoma-bearing mice. METHODS: DOX-loaded liposomes were prepared with (i) specific monoclonal IgG3 antibody (32/2, D-SSIL-32/2); (ii) non-specific IgG3 (D-SSIL-IgG); or (iii) no IgG (D-SSL) on their surface. Equal DOX amounts were injected intravenously via each type of liposome into BALB/c mice carrying experimental lung metastases of a polyoma virus-induced fibrosarcoma (A9 ctc 220) expressing a polyoma virus-induced tumor-associated antigen (PAA) on their surface. Metastases occurred mainly in lung. Mice were treated at 3 stages of tumor development (micrometastases, medium-size metastases, and large, necrotic metastases). Performance evaluation was based on time-dependent quantification of DOX and DOX metabolites (DOX-M) in lung tumor, noncancerous organs, and plasma. RESULTS: (i) DOX delivered via both SSIL retained the prolonged circulation time typical of DOX delivered via D-SSL. (ii) DOX accumulation in noncancerous organs was similar for all preparations. Low levels of DOX-M were obtained for all three preparations in all organs except liver, suggesting a similar processing. (iii) Preparations differed in behavior in lung tumor depending on tumor size and microanatomy. Only at the micrometastases stage were the specifically targeted D-SSIL-32/2 superior to D-SSL and D-SSIL-IgG, delivering 2-4 times more drug into the tumor. (iv) DOX-M level in all three tumor stages was in the following order: D-SSIL-32/2 > > D-SSL > > D-SSIL-IgG, suggesting that DOX delivered as D-SSIL-32/2 is most available to tumor cells. CONCLUSIONS: The advantage of specific targeting of sterically stabilized liposomes is expressed mainly in increasing availability of DOX to tumor cells in a way which is dependent on tumor microanatomy. The impact of this advantage to therapeutic efficacy remains to be determined.

Preparation and characterization of doxorubicin-loaded sterically stabilized immunoliposomes.

PURPOSE: To compare the performance of sterically stabilized, doxorubicin-loaded liposomes with and without surface attached specific antibodies (D-SSIL and D-SSL, respectively). METHODS: Small (< or = 120 nm) unilamellar liposomes were prepared composed of hydrogenated soy phosphatidylcholine, hydrogenated phosphatidylethanolamine (HPE), cholesterol, and 2000Da polyethylene glycol (2000PEG) attached to the primary amino group of distearoyl phosphatidylethanolamine. Doxorubicin was remote-loaded into these liposomes by an ammonium sulfate gradient to form the D-SSL. Monoclonal IgG3 NI32/2 antibodies directed against a polyoma virus tumor-associated antigen expressed on A9 ctc 102 murine fibrosarcoma cells were attached to the D-SSL HPE via a thioether bond to form the D-SSIL-32/2. A control of nonspecific D-SSIL was prepared by attaching nonspecific IgG3-enriched immunoglobulins to D-SSL. All liposomes were physically and chemically characterized and then tested in vitro for tumor cell binding, specificity, and uptake by macrophages; and in vivo for the drug plasma pharmacokinetics after intravenous administration in mice. RESULTS: (i) The attachment of antibodies to D-SSL did not impair their chemical or physical stability and had a minimal effect on their size and level of loaded drug. (ii) The combination of specific antibodies and 2000PEG grafted in the liposomes improved the specific binding to relevant target cells by reducing the level of unspecific binding to nonrelevant cells. (iii) D-SSIL retained the prolonged circulation and slow clearance typical of SSL lacking the antibodies. CONCLUSIONS: Sterically stabilized immunoliposomes exhibited stability, ability to recognize target cells, and prolonged circulation time. This study also shows that it is feasible to prepare them in pharmaceutically acceptable dosage form. Thus, further investigation for tumor targeting and efficacy is warranted.

[Correlation of the relative population count of ixodid ticks with various recording methods]. / O sootnoshenii otnositel'noi chislennosti iksodovykh kleshchei pri razlichnykh metodakh ucheta.

Data are given on the relative abundance ratio of 3 species of ixodid ticks obtained by different counting methods.

[Characteristics of the relation of tick-borne encephalitis morbidity to natural factors]. / Ob osobennostiakh sviazi zabolevaemosti kleshchevym éntsefalitom s prirodnymi faktorami.

Data and tendencies characteristic of relationship between the severity of the course of tick-borne encephalitis and a number of biotic and climatic factors have been revealed by the method of information analysis. On the basis of relationships established in this study the authors make a suggestion concerning two most important stages in the formation and manifestation of the clinical features of tick-borne encephalitis in different areas of endemic territories, linked, on one hand, with the population selection of the infective agent and, on the other hand, with temperature conditions and the duration of the cold season.