Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation.

Permeability of the blood-brain barrier for protein fractions 50-100 kDa (PF50-100) of Cellex Daily preparation labeled with fluorescent tracer FITC and non-conjugated FITC were compared after intranasal administration of the preparations to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid samples showed that Cellex Daily PF50-100-FITC administered intranasally penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2 h after administration and persists in the circulation for 24 h probably due to binding with plasma proteins. The differences in the kinetic profile of PF50-100-FITC and free FITC indirectly suggest that the major part of the preparation is not degraded within 24 h and FITC is probably not cleaved from the protein components of the preparation. In vivo fluorescence analysis showed significant fluorescent signal in the olfactory bulbs in 6 h after intranasal administration; hence, the preparation administered via this route can bypass the blood-brain barrier. Scanning laser confocal microscopy of rat brain sections confirmed penetration of the high-molecular weight protein fraction PF50-100-FITC into CNS structures. The most pronounced accumulation of the labeled drug was observed in the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC administered in the control group, significant accumulation of PF50-100-FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.

Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer.

Modeling and integral X-ray, optical, and MRI visualization of multiorgan metastases of orthotopic 4T1 breast carcinoma in BALB/c mice.

A model of highly metastasizing orthotopic allogeneic breast carcinoma was reproduced and standardized in experiments on BALB/c mice. 4T1 cells characterized by high metastatic activity were transfected with red fluorescent protein (RFP) gene or firefly luciferase (Luc2) gene. Unmodified 4T1 cells and modified 4T1-RFP and 4T1-Luc2 cells were subcutaneously injected to mature female mice into the second mammary fat pads. Quantitative evaluation of the primary node and visceral metastases was performed using magnetic-resonance imaging, X-ray and optical tomography. Modification of 4T1 cells with RFP gene considerably reduced their invasive and metastatic potential and led to spontaneous regression of the primary tumor in 20% cases. Modification of 4T1 cells with Luc2 gene had practically no effect on proliferative, invasive, and metastatic characteristics of the tumor and provided the possibility of quantitative analysis of the primary tumor dynamics by the luminescence intensity. The survival median in mice receiving unmodified 4T1 cells and transfected 4T1-RFP and 4Т1-Luc2 cells was 32, 42, and 38 days, respectively. Neither primary node nor tumor metastases accumulated gadolinium-containing contrast agent and Alasens fluorescent tracer. After implantation of 4T1 and 4Т1-Luc2 cells, multiple metastases were more often detected in the lungs, liver, spleen, spine, and regional lymph nodes and less frequently in the brain, which corresponded to metastasizing profile of human breast cancer. The developed model of orthotopic breast carcinoma 4T1 in BALB/c mice with complex detection of multiple organ metastases using X-ray microCT, optical, and MRI can be recommended for preclinical studies of new antitumor preparations.

[The impact of electromagnetic radiation at microwave frequency (9.8 HhZ)on the embryonic and postembryonic development of the tick Hyalomma asiaticum (Acarina, Ixodidae)]. / Vliianie élektromagnitnogo izlucheniia svch diapazona (9.8 ggts) na émbrional'noe i postémbrional'noe razvitie kleshcha Hyalomma asiaticum (Acarina, Ixodidae).

Low-power (20 microW/cm2) microwave-modulated radiation at a carrier frequency of 9.8 Hhz is shown to affect the course and specific features of ontogenesis of the ick H. asiaticum. The actin of microwave radiation on the development of H. asiaticum substantially depends on the frequency of microwave modulation of a signal and on the temperatures of an experiment. When the temperature is 22 degrees C, there is a significant suppression of development of fed larvae and nymphs after exposure to microwave radiation at modulated signal frequencies of 3 and 5 Hz/ The whole range of the tested modulation frequencies was 2 to 16 Hz. The hungry species of all developmental phases in H. asiaticum were virtually unresponsive to exposures. At 14 degrees C (a perithreshold temperature of H. asiaticum development), the action of microwave radiation changed from inhibitory to stimulating. At modulation frequencies of 3, 5 and 7 Hz, the proportion of hatching larvae was 42.5, 67.5 and 80.0%, respectively, and that of controls was 2.5%. Whether the size of a H.asiaticum population can be controlled by a radar that provokes the development of ticks before winter by its radiation is discussed.

[The reaction of the tick Hyalomma asiaticum (Acarina, Ixodidae) to 1- to 4-GHz microwaves]. / Reaktsiia kleshscha Hyalomma asiaticum (Acarina, Ixodidae) na mikrovolny 1--4 GGts.

Low-energy microwave radiation in the frequency range in question was found to exert a noticeable biological action on H. asiaticum. Radiation delayed larval hatch by 3-20 days, increased the activity duration of newly moulted larvae by 17-24 days, reduces the survival of hungry larvae and nymphs by 4-10 days. The efficiency of the biological action of microwaves is enhanced by impairments in the natural developmental rhythm of the tick.

[The effect of microwaves (UHF) and magnetic fields on the insecticidal properties of biological and chemical preparations]. / Vliianie mikrovoln (SVCh) i magnitnykh polei na insektitsidnye svoistva biologicheskikh i khimicheskikh preparatov.

The larvicidal activity of preparations from different groups of compounds was assayed after their exposure to microwaves and magnetic field. The radiation was found to have a varying impact on the insecticidal properties of the preparations. Thus, the efficiency of spheric larvicides decreased, which is likely to be associated with the structural changes of toxin crystals, whereas the larvicidal activity of the organophosphorus compound dursban and the pyrethroid aikon increased 2-5-fold. The higher activity of dursban irradiated with a magnetic field was demonstrated to retain for over 2 months.

[Changes in the acaricidal properties of organophosphorus compounds under the influence of magnetic resonance treatment]. / Izmenenie akaritsidnykh svoistv fosfororganicheskikh soedinenii pod vliianiem magnitorezonansnoi obrabotki.

The authors demonstrate the possibility of enhancing pesticidal properties of some organophosphorus compounds by their single treatment for 40 min by pulsed magnetic field, 100 kHz, 10-15 microT with 16 Hz sinusoidal modulation. The treatment efficacy is up to 30 days.

[Effect of local SHF-irradiation of the rat foot on impulse activity in the tibial nerve]. / Vliianie lokal'nogo SVCh-oblucheniia stopy krysy na impul'snuiu aktivnost' v bol'shebertsovom nerve.

In experiments on rats the effects of 2.45 GHz microwave radiation on impulse activity of the afferent structures were studied in single afferent fibres of n. tibialis. Microwaves of both low and high intensity (from 0.04 to 100 mW/cm2) were shown to modify the impulse activity of the afferents which was mainly displayed by the increase in a current average frequency of impulse activity.

[Mechanism of the effect of nonionizing radiation on animals at the level of sensory systems]. / K voprosu o mekhanizmakh deistviia neioniziruiushchikh izluchenii s zhivym organizmom na urovne sensornykh sistem.

In three series of experiments on mice (CBA X C57BL)F1 and Wistar rats a study was made of the effect of microwaves (0.9 GGz, 0.4 mW/cm2, 10 min) on the EEG reaction of adopting the photostimulation rhythm by rats; the effect of microwaves (0.6 GGZ, 0.04 mW/cm2, 5 min) and gamma-quanta (60Co, 0.5 Gy) on the reaction of avoiding by mice of cooled surfaces, and the effect of microwaves (9.8 GGz, 0.04 mW/cm2, 5 min) on the reaction of avoiding the water pool. The results obtained are discussed with regard to the hypothesis that the biological effects of weak microwave radiation may be realized at the nervous system level via cutaneous ceptors.