Interaction with serum albumin as a factor of the photodynamic efficacy of novel bacteriopurpurinimide derivatives.

Optimization of the chemical structure of antitumor photosensitizers (PSs) is aimed at increasing their affinity to a transport protein, albumin and irreversible light-induced tumor cell damage. Bacteriopurpurinimide derivatives are promising PSs thanks to their ability to absorb light in the near infrared spectral region. Using spectrophotometry, we show that two new bacteriopurpurinimide derivatives with different substituents at the N atoms of the imide exocycle and the pyrrole ring A are capable of forming non-covalent complexes with human serum albumin (HSA). The association constant (calculated with the Benesi-Hildebrand equation) for N-ethoxybacteriopurpurinimide ethyloxime (compound 1) is higher than that for the methyl ether of methoxybacteriopurpurinimide (compound 2) (1.18×10(5) M-1 vs. 1.26×10(4) M(-1), respectively). Molecular modeling provides details of the atomic interactions between 1 and 2 and amino acid residues in the FA1 binding site of HSA. The ethoxy group stabilizes the position of 1 within this site due to hydrophobic interaction with the protein. The higher affinity of 1 for HSA makes this compound more potent than 2 in photodynamic therapy for cultured human colon carcinoma cells. Photoactivation of 1 and 2 in cells induces rapid (within a few minutes of irradiation) necrosis. This mechanism of cell death may be efficient for eliminating tumors resistant to other therapies.

[The directions and experiences of integration of clinical laboratory diagnostic and branch medicine].

The article considers the actual issues of teaching laboratory medicine to students of medical faculty and to physicians getting trained in different programs of postgraduate education. The major models of interaction between clinical physicians and specialists of laboratory diagnostic are considered. The proposed model of teaching of laboratory medicine is developed in collaboration with clinical chairs and is based on the principle of "clinical laboratory council of physicians". The analysis of clinical cases of specific patients and clinical analytical critiques are in the basement of the given system. The algorithm of considering one of situation tasks used in teaching is presented as example.

[In memory of Yuri Sergeevich Balashov (25.XII.1931-28.IX.2012)].

Biographical notes describe the life and scientific activities of Yuri Balashov, an outstanding Russian parasitologist, the Chief Editor of Parazitologiya.

[Characteristic features of biodiversity in European ixodid ticks (Acari, Ixodidae) as vectors of diseses with natural foci].

The diapason of some biodiversity characteristics of ixodid ticks of the fauna of Europe and adjacent territories is analyzed. These characteristics include taxonomic and morphological diversity, the diversity of life cycles, host-parasite relations, species ranges, and biotopic associations. The significance of different aspects of biodiversity of ixodid ticks as a prerequisite of interrelations with pathogens with natural foci is estimated.

[Collection of ixodoid ticks in the Zoological Institute of Russian Academy of Sciences: its unique features and significance for decoding fundumental aspects of taxonomy and those connected with natural reservoirs].

Unique features of the collection of ixodoid ticks in the Zoological Institute of Russian Academy of Sciences (St. Petersburg, Russia) are characterized. The collection is stand out against a background of other world's collections by the presence of complete geographic series from whole ranges of species, including all active stages of ontogenesis. The results of basic and applied investigations obtained owing to the characteristics of this collection are summarized briefly. The contribution to the taxonomic investigations of ixodoid ticks connected with the problem of natural foci, based on the collection, is analyzed. Urgent directions of ongoing and future studies based on the collection are considered.

[Characteristic features of the ranks genus and subgenus, and an intercalary rank "species complex" in ixodid ticks (Acari: Ixodidae)].

The work was carries our from the standpoint of the morphological conception of species. Vast collections of the Zoological Institute of the Russian Academy of Science testify to the existence of hiatuses in both genera and subgenera of Palearctic ixodids at all active phases of their ontogenesis. The fact that the subgenera of Palearctic genera have been well studies is notes, and composition of the subgenera is presented. The question of a taxonomic intercalary rank "species complex" is considered in detail in the context of the coevolution between some complexes of closely related species of ixodid ticks and some closely related species (genospecies, strains) of pathogens. The question of the taxonomic rank "species complex" in ixodid ticks as a phyletic species association is postulated on the basis of comparative ontogenetic data. Nomenclature status of the intercalary association "species complex" is specified in conformity with the fourth edition of the International Code of Zoological Nomenclature. Species composition of most studied complexes is presented. Some variants of morphological differentiation between species complexes within subgenus are considered. Significance of the taxonomic concept "species complex" for zoological. parasitological, and medical aspects of the ixodid ticks study was evaluated. Prognostic significance of the rank "species complex" for the study of the relationships between ixodid ticks and pathogens is discussed.

[Larval identification of species and subspecies of the genus Hyalomma (Acari: Ixodidae) from Russia and neighbouring territories].

The following species and subspecies of Hyalomma Koch, 1844 are recorded from Russia and neighbouring territories, including those involved in natural foci of tick-borne diseases: H. (Hyalomma) aegyptium (Linnaeus, 1758), H. (Euhyalomma) dromedarii Koch, 1844, H. (Euh.) asiaticum asiaticum Schulze et Schlottke, 1930, H. (Euh.) asiaticum caucasicum Pomerantzev, 1940, H. (Euh.) asiaticum kozlovi Olenev, 1931, H. (Euh.) anatolicum Koch, 1844, H. (Euh.) excavatum Koch, 1844, H. scupense Schulze, 1918, H. (Euh.) marginatum marginatum Koch, 1844, H. (Euh.) marginatum turanicum Pomerantzev, 1946, and H. (Euh.) marginatum rufipes Koch, 1844. The geographic distribution and host-parasite relationships of each taxon are discussed. Species characters of the larval stage, that can be distinguished using light microscopy, are found to be very few. These characters include shape of scutum, shape and rate of hypostome denticulation, shape and rate of the development of spurs on coxae I to III. Measurements of some morphological structure and their rations show statistically significant differences between some closely related species, even if qualitative discriminating characters are unknown. Only measurements and their ratios can be used for the discrimination of larval H. anatolicum from larval H. excavatum, because qualitative discriminating features have not been found for these species. The complex structure of the subspecific morhological differentiation of all parasitic stages in the polymorphic species H. asiaticum and H. marginatum is revealed. This structure probably reflects some peculiarities of the microevolutionary processes. Identification key for the larval stage of seven Hyalomma species is provided.

[Diagnosis of pigment-free optic tract tumors: clinical and morphoimmunohistochemical aspects].

The authors present the results of comparison of clinical, instrumental and histological, immunohistochemical and electron microscopic data on two pigment-free ciliochoroidal tumors. Differential diagnosis was made at each of the above stages of diagnosis. There is evidence that despite the similarity of the clinical syndrome, the spindle-cell type of the histological structure of both tumors, the latter were of various histogenesis. This was confirmed by the results of immunohistochemical and electron microscopic studies. Retrospective analysis of the data of immunohistochemical and echographic studies revealed the distinctive signs that could differentiate these two types of tumors at the stage of clinical and instrumental diagnosis.

[Assessment of the preimaginal stages of the ticks collected from small mammals in Western and Northern Caucasus (Acari: Ixodidae)].

The exact identification of the preimaginal stages of the ticks collected from small mammals in Western and Northern Caucasus as a result of ten-year route investigations allowed us to obtain new data on the geographic ranges, altitude and biotopic preferences, and host-parasite relations of 11 species. A wide range of the joint occurrence (in the same locality, on the same host species, on the same host individual) is recorded for the first time for 10 species. The cohabitation of the each of 10 species with other 2-9 species has been found. The number of the cases of joint occurrence of different ixodid species on the same host individual is proportionate to the collection period in one locality. The cohabitation did not observed only for the species Ixodes ghilarovi, a high mountain ixodid species, which is for the first time recorded in 7 localities of Northern and Western Caucasus.

Reduction of phase thickness is a characteristic reaction of the nucleoli to toxicity as shown by coherent phase microscopy.

Optical parameters of human cell nucleoli (HCT116 colorectal cancer cells) in depolymerization of microtubules and depletion of intracellular ATP pool were studied by coherent phase microscopy. These influences were associated with a rapid (recorded within the first minutes) reduction of the phase thickness of the nucleoli. These changes are similar to the nucleolar response to direct inhibitors of transcription. Hence, quantitative parameters of coherent phase microscopy describe common reaction of the nucleolus to stress; reduction of optical thickness of the nucleolus is a component of this reaction.

[Intraspecific taxonomic differentiation in ticks (Acari: Ixodidae) in the view of the morphological conception of species].

The criterions for two most used intraspecific taxonomic ranks of ticks--subspecies and morphotype, have been formulated on the basis of the study of morphological variation in the distribution range of all active ontogenetic stages of 11 polymorphic species. All these species are vectors of transmissible diseases. They have vast distribution ranges and different types of host-parasite relationships. Subspecies have the complexes of visual morphological differences expressed in one or both sexes of mature ticks more limited, than those of related species. At immature stages differences of subspecies consist more often in morphometric characters and can be established by the methods of mathematical statistics only. Morphotypes, as a rule, differ at each corresponding stage by "their own" complexes of morphometric characters. All differential parameters of studied morphotypes are overlapped, but have statistically significant differences (by the Student's test). The concrete variations of differentiation by subspecies and morphotypes have been considered. The historical factors of intraspecific differentiation have been reconstructed for each species.

[Morphological inversions during the ontogenesis of the ixodid ticks (Acari: Ixodidae) from the viewpoint of the hypermorphosis conception and their significance for systematics].

Morphological inversions during the ontogenesis of the ixodid ticks consist in the deranges of species-specific tendencies in the development of some external structures by the female line. The inversions, which included a wide range of organs and their fine structures, have been described for the first time in 14 species of 4 from 7 Palearctic ixodid genera. Emphasis is placed on the study of the structures, which serve as differential characters for closely related species. It is shown, that the using of the structures subjected to inversions is unavoidable in systematics because of the great similarity of closely related species, especially in immature stages. It is established by the data on the variability of all active stages in the species distribution ranges, that the degree of the inversions manifestation may somewhat fluctuate in different subspecies or geographic morphotypes of the same species, but the peculiarity of the inversions always remains a species-specific character. The cause of inversions origin is the evolution of the Ixodidae by the way of morpho-ecological specialization, namely hypertrophic, giantism, the growth of teguments in the period of nutrition act by pasture ambushing, which led to the derange of the development coordination of the organs during ontogenesis. Biological implication of the inversions is a guarantee of the adaptive potential of species during the process of microevolution. Even though the inversions make identification of closely related species difficult, their substantial importance is that they form integral species-specific character for the whole active part of the species ontogenesis.

[Morphological characteristics of stromal gastrointestinal tumors].

Stromal tumors are singled out from smooth muscle and neurogenic neoplasms into a special group due to differences in CD117 expression caused by mutation of c-kit gene. Out of 57 stromal tumors, 37 (64,9%) located in the stomach, 17 (29,8%) in the small intestine and 3 (5,3%) in the colon. Immunohistochemically, all the tumors expressed CD117 and vimentine. Smooth muscle actin was found in 82% tumors, S-100 protein in 75%, neuron-specific enolase in 66% cases. Malignant tumors were in 93% cases, and in 7% benign. Metastases were observed in 47.7% cases, recurrences in 14%. The liver was most frequent site of metastases (88.9%), peritoneum (51.9%). 21% patients died of progression of the underlying disease during the follow-up of 6-60 months.

Study of optical parameters of the nucleoli under the effect of transcription inhibitors by coherent phase microscopy.

The use of coherent phase microscopy for online quantitative registration of nucleolar reaction to transcription inhibition is validated. Reduction of phase thickness of the nucleoli was detected during the first minutes of the experiment; 30 min after addition of the drug rarefaction zones predominated and areas of condensation were seen. These changes reflect the dynamics of disorders in the nucleolar ultrastructure during transcription inhibition.

[Some aspects of intraspecific variability of the closely related species of the Dermacentor marginatus complex (Acari: Ixodidae) as demonstration of microevolutionary process].

Individual and geographical variability of male conscutum pattern in five closely related species of the Dermacentor marginatus complex (D. marginatus, D. ushakovae, D. niveus, D. silvarum, D. nuttalli) has been examined. The pattern has been examined in three to six geographical samples within each specific distribution range. It was established that the pattern of the conscutum central area is subjected to individual and geographical variability on an extreme degree and gives very few intraspecific differential characters, but it shows interspecific differences in some cases. However the dark patches of marginal flank (npkappadelta and 3deltakappa respectively, see Fig. 3) show statistically significant differences in length in all geographical samples of the first four species. Characteristic features of ixodid ticks morpogenesis rule out to a considerable extent the possibility to trace geographical variability of the same characters by all stages of ontogenesis. In these cases, when it is possible, the tendencies to variability on different stages do not always coincide. There is no coordination within the species in the degree of differences of examined geographical samples by pattern and morphological characters, i. e. very complex polymorphis is observed. In the context of the evolution that kind of polymorphism of the geographical samples has provided the species with high adaptive potential for conquest of the extensive range and maintaining large numbers. The question of allopatric speciation of the closely related D. marginatus-D. silvarum with small secondary area of transgression their ranges, and sympatric speciation of the D. ushakovae-D. niveus is postulated.

Olivomycin induces tumor cell apoptosis and suppresses p53-induced transcription.

Olivomycin (DNA-binding antibiotic) in nanomolar concentrations induces apoptosis of human tumor cells and inhibits p53-dependent transcription of the reporter gene (basal and induced by antitumor drugs). Olivomycin aglycon induces no cytotoxicity and does not block transcription.

[Variability of the hard dorsal idiosomal tegument pattern and other phenotypic characters as a manifestation of microevolution in Dermacentor marginatus (Acari: Ixodidae)]. / Izmenchivost' risunka tverdykh dorsal'nykh pokrovov idiosomy i drugikh fenotipicheskikh priznakov kak proiavlenie mikroévoliutsii vida Dermacentor marginatus (Acari: Ixodidae).

The pattern of male conscutum and female scutum in Dermacentor marginatus has been examined in 6 points of the East-European and Asian parts of its range (Fig. 1). A high rate of modification variability of the pattern has been recovered in each geographical sample. It is shown that populations differ reliably from each other by the length of the dark patches on the marginal flank of the conscutum (nkappabeta, npkappabeta, 3kappabeta); some samples also differ by the number of these patches, complexes of other patches of the scutum and conscutum, and as well (visually) by the color density of light fields and contrast between them and the dark background on the conscutum and scutum (Table 1, 2). Besides, the samples differ reliably at each stage by the complexes of morphometric characters (Table 3, 4). The sample from the Peter the First Ridge is most deviate from others by the color contrast and complex of patches both in males and females. However, by the patches of marginal flank and morphometric characters of both sexes and perimaginal stages this sample differ less from others. The sample from the Stavropol plateau having most variable pattern (Fig. 3, 1-9, 4, 1-3) is characterized by the greater number of statistically reliable differences by the patches (nkappabeta, npkappabeta, 3kappabeta) and morphometric characters of all stages of the ontogenesis from all other samples. Other geographical samples have intermedial position in regard to degree of differences from each other. The samples examined are considered as morphotypes; degree of differences between morphotypes is unequal. The phenotypic differences have mosaic dispersion among ontogenetic stages and do not show a coherent direction in comparing the morphotypes. Differential characters of the morphotypes and related tick species belong to different structures or their different parameters. Possible ways of morphotype's origin and geochronological characteristics of morphotypes are discussed.