[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

[Possibilities of using Cytoflavin in the treatment of cognitive and emotional disorders in patients with tension headaches]. / Vozmozhnosti primeneniia Tsitoflavina pri lechenii kognitivnykh i émotsional'nykh narushenii u patsientov s golovnymi boliami napriazheniia.

OBJECTIVE: To evaluate the efficacy and safety of Сytoflavin in the treatment of cognitive and emotional disorders in patients with tension headache. MATERIAL AND METHODS: Fifty patients with tension headache, aged from 18 to 50 years, were studied. The following methods and tests were used: neurological examination, NPRS, STAI, CFQ, RAVLT, TOVA, electroencephalography (routine and spectral analysis). The patients were treated with Сytoflavin. RESULTS: After the treatment, clinical improvement was observed in 62.0% of the patients. A significant decrease in trait anxiety and inattention, as well as an improvement of memory performance were observed. A comparative analysis of neurophysiological results before and after the treatment showed a decrease in the manifestations of dysfunction of nonspecific regulation of the brain. CONCLUSION: The results of this study demonstrate the efficacy of Cytoflavin in the treatment of tension headache and associated emotional and cognitive impairments.

[Length of Meristematic and Fully Elongated Root Cells Related to Haploid DNA Content].

The lengths of meristematic (l(m)) and fully-elongated cells (l(e)) were measured in the roots of 118 monocot and dicot species of herbaceous plants from 20 angiosperm families. The results were analyzed using the data on haploid DNA content (C(val)) for the same species from the website (http://data.kew.org/cvalues). The distribution range of lm, le, and C(val) was wider in monocot plants compared to dicots. Values of l(m) and l(e) in monocot and lm in dicot species correlated positively with C(val). Dependence of lm and le on C(val) was similar in diploid and polyploid species, both monocots and dicots. The average length of root cells differed less than the root length.

[The role of ethylene in activation division cell quiescent center in the cut maize roots].

In the present work we used two maize cultivars in which root meristem responded differently to root tip excision: in Interkras-375 MW we observed meristem opening due to the activation of cell divisions in the quiescent center (QC), while in Krasnodar-194 MW the meristem remained closed. Excised root tips of Interkras M B-375 were shown to produce much more ethylene than excised root tips of Krasnodar-194 MW The inhibitor of ethylene biosynthesis L-α-ethoxyvinyl 2amino-glycine-HCl (AVG) and inhibitors of ethylene action AgNO3 and 1-methyl-cyclopropene (MCP) prevented meristem opening in excised root tips of Intekras-375 MW. The obtained results allow us to conclude that ethylene plays an important role in the activation of cell divisions in the QC of excised root tips.

A novel Dictyostelium cell surface protein important for both cell adhesion and cell sorting.

A mutant of Dictyostelium that is aberrant in the process of tip formation (dtfA-: defective in tip formation A) has been isolated by gene tagging. The dtfA gene is predicted to encode a protein of 163 kDa. There are no extensive sequence homologies between DTFA and previously identified proteins, but four short N-terminal sequence motifs show partial homology to repeats found in mammalian mucins. Immunofluorescence reveals a lattice-like arrangement of DTFA protein at the cell surface. When developing on a bacterial lawn, cells of the mutant strain (dtfA- cells) aggregate to form tight mounds, but development then becomes arrested. When developed in the absence of nutrients, a fraction of dtfA- cells complete development, but there is a long delay at the tight mound stage and the culminants that eventually form are aberrant. In such dtfA- mounds the prestalk cells fail to move to the apex on cue and so tip formation is delayed. dtfA- cells also show a conditional defect in early development, in that they are unable to aggregate when plated at low density. In addition dtfA- cells do not agglomerate efficiently when shaken in suspension. In combination, these results suggest that DTFA may form part of a cell-cell adhesion system that is needed both for optimal aggregation and for efficient cell sorting during multicellular development. The DTFA protein also appears to be important during cell growth, because cytokinesis is defective and the actin cytoskeleton aberrant in growing dtfA- cells.

SH2 signaling in a lower eukaryote: a STAT protein that regulates stalk cell differentiation in dictyostelium.

The TTGA-binding factor is a transcriptional regulator activated by DIF, the chlorinated hexaphenone that induces prestalk cell differentiation in Dictyostelium. The same activity also functions as a repressor, controlling stalk cell differentiation. We show that the TTGA-binding factor is a STAT protein. Like the metazoan STATs, it functions via the reciprocal interaction of a phosphotyrosine residue on one molecule with an SH2 domain on a dimerizing partner. Furthermore, it will bind specifically to a mammalian interferon-stimulated response element. In Saccharomyces cerevisiae, where the entire genomic sequence is known, SH2 domains have not been identified. It would seem, therefore, that SH2 signaling pathways arose very early in the evolution of multicellular organisms, perhaps to facilitate intercellular comunication.

Effect of age on development of tumours in the intrasplenic ovarian grafts in ovariectomized rats.

Female rats at the age of 1, 3, and 14-16 months ("young", "adult" and "old" groups respectively) were bilaterally ovariectomized and one of the removed ovaries was autoimplanted into the spleen. The total intrasplenic ovarian tumour incidence was equal in the rats subjected to the operation at 3 and 14-16 months (77.4% and 80.6% respectively) and tumours developed more frequently in rats exposed to surgery at the age of 1 month (94.5%), P < 0.05. The incidence of Sertoli and Leydig cell tumours was increased and their latency was decreased in the old group in comparison to the adult one. In rats exposed to the operation at the age of 3 months, granulosotheca cell tumours developed more frequently than other tumour types, and in the young group thecomas were discovered more often than in both older groups. Dysgerminomas and luteomas were discovered only in intrasplenic grafts of rats of the young group. It is supposed that the differences in structure and proliferative activity of various ovarian tissues between young, adult and old rats at the moment of intrasplenic transplantation, as well as the differences in their response to gonadotropic stimulation play a significant role in the development of ovarian tumours of varied histogenesis in the intrasplenic ovarian grafts.

Age-dependent antileukemic action and suppression of immune response by 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) in mice.

The antineoplastic activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) against murine leukemia P388 was found to be markedly reduced in 12- and 18-month-old mice as compared to young animals. The immune response against sheep red blood cells (SRBC), a T cell-dependent antigen, was also strongly diminished in tumor-free old mice and was further suppressed after ambazone treatment. Since the antileukemic effect of ambazone disappeared more or less in congenitally athymic nude mice, in neonatally thymectomized or silica-pretreated animals, it has been concluded that the action of the compound seems to be limited to young adult immunocompetent tumor-bearing hosts. Therefore immunosenescence, primarily of T cell functions of old tumor-bearers, may represent a decisive factor influencing the antileukemic, especially curative effect of ambazone in aged animals. A combined treatment with ambazone and immunomodulators (thymalin or a splenopentin derivative) failed to improve the antileukemic effect in young and old leukemia P388-bearing mice.

Influence of host age on lung colony forming capacity of injected rat rhabdomyosarcoma cells.

Intravenous administration of RA-2 transplantable rhabdomyosarcoma cells produces development of metastatic tumour cell colonies in the lungs of host rats. After administration of 2 X 10(3), 5 X 10(3) or 10 X 10(3) RA-2 cells, different patterns of dependence of the number of metastatic clones in the lungs on injected cell number have been observed. The numbers of tumour cell colonies were shown to be highest in immature (1-month-old) and old (15-month-old) female rats compared to middle-age groups (3- and 12-month-old). A similar age-related pattern was observed in male rats. Analysis of the results obtained has revealed positive correlation between tumour cell colony numbers and both somatomedin activity and proliferation rate of neoplastic tissue.

Carcinogenesis and aging. VIII. Effect of host age on tumour growth, metastatic potential, and chemotherapeutic sensitivity to 1.4-benzoquinone-guanylhydrazonethiosemicarbazone (ambazone) and 5-fluorouracil in mice and rats.

Mice and rats of various ages (3, 10-12, and 18-19 months) were inoculated with the transplantation tumours murine melanoma B16 (B16), mammary adenocarcinoma 755 (Ca-755), leukemia P388 (P388), and rat rhabdomyosarcoma RA-2 (RA-2). Subcutaneous (sc) growth of B16 was not markedly affected by the age of the syngeneic host whereas intravenously (iv) inoculated 12 months old C57BL/6 mice developed more pulmonary metastases than animals 3 months of age. Median survival time (MST) of 18 months old mice bearing Ca-755 was significantly shorter than that of younger individuals. In contrast, old rats that had been injected RA-2 iv survived longer than controls. Survival of DBA/2 mice inoculated intraperitoneally (ip) with P388 cells was not influenced by the age of the host. The antineoplastic activity of ambazone and, to a less extent, of 5-fluorouracil against P388 was drastically lower in 12 months old mice than in 3 months old tumour bearers. Likewise a graduate loss of antineoplastic activity of ambazone against Ca-755 was observed with increasing age of the mice, whereas the effect of ambazone and 5-fluorouracil against RA-2 did not depend on the age of the rats. It is suggested that tumour-host interactions as well as pharmacokinetics of a given drug may underlie age-related changes.