Pharmacological Analysis of the Therapeutic Effect of Radioprotectors Cystamine and Indralin in the Capacity of Radiomitigators.

The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body 60Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α1-adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT2 serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.

Radioprotective Properties of Indralin in Combination with Monizol in the Treatment of Local Acute and Delayed Radiation Injuries Caused by Local Skin γ-Irradiation.

Female rats were exposed to local γ-irradiation of the right hindpaw in doses of 30-50 Gy at 131-154 sGy/min dose rate. Radioprotector indralin was administered per os 15 min prior to irradiation, monizol was injected intraperitoneally 5 min after irradiation. Indralin showed marked radioprotective properties both for acute and delayed symptoms of local radiation injuries. In combination with monizol, radioprotective effect of indralin was potentiated to dose reduction factor of 1.4-1.5 both for radiation burn severity reduction and for restriction of postradiational contracture development and amputation of the irradiated limb.

Therapeutic effect of long-term melatonin treatment on the course and fatal outcome of modeled acute radiation sickness.

We studied the effect of long-term administration of melatonin to male C57Bl/6 mice starting from day 3 after whole-body γ-irradiation (9.5-10.0 Gy, 7.7-17.1 cGy/min). It was found that replacement of drinking water with melatonin solution (5 mg/liter) did not reduce the amount of fluid intake throughout the period of acute radiation injury. The daily dose of melatonin was 0.9-1.2 mg/kg body weight (this parameter was lower at the peak of the disease and increased during the recovery stage). Melatonin by more than 20% (p<0.05) improved survival of mice exposed to γ-irradiation in a dose of LD97/30, reduced leukopenia during the stage of acute manifestations of the disease and maximum mortality, and increased blood leukocyte count by 40% (p<0.05) by day 12 after irradiation.

[Systematization and hygienic standardization of environmental factors on the basis of common graphic models].

On the basis of graphic models of the human response to environmental factors, two main types of complex quantitative influence as well as interrelation between determined effects at the level of an individual, and stochastic effects on population were revealed. Two main kinds of factors have been suggested to be distinguished. They are essential factors and accidental factors. The essential factors are common for environment. The accidental factors are foreign for environment. The above two kinds are different in approaches of hygienic standardization Accidental factors need a dot-like approach, whereas a two-level range approach is suitable for the essential factors.

[Radioprotective properties of indralin combined with cystamine and mexamine].

The study of indralin radioprotective properties at its joint application with cystamine and mexamine was carried out in the experiments on inbred mice and rats. The mice and rats were exposed to whole-body y-irradiation at a dose of 9.0 and 9.5 Gy, correspondingly. A combined parenteral administration ofindralin and cystamine at a dose of 25 mg/kg showed ponentiaton of indralin radioprotective properties up to a level of the ED50 effect versus the absence of or a weak radioprotective effect in the case of their separate application. In the experiments on rats, indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally almost completely eliminated the animal mortality from the intestinal syndrome of acute radiation sickness amounting in the control radiation group to 60% on the 7th day after exposure to radiation at a dose of 9.5 Gy. However, at the above conditions, radioprotectors at these doses had a low-level radioprotective action at the onset of the bone marrow syndrome of acute radiation sickness. Combined application of indralin and mexamine at the same doses and at the same conditions led to a radiation protection 50% as high as in the case when radioprotectors were applied separately at a double dose.

[The influence of combined application of quercetin and indralin on post-irradiation repair of hematopoiesis in acute radiation injury].

Experiments on mice-hybrids F1(CBA x C57B1/6) have detected a favorable effect of the associated application of quercetin (30-60 minutes before y-exposure of an animal) and a radioprotectant of urgent action indralin (in the case of its application after y-exposure) on a post-irradiation repair of the hematopoietic tissue in acute radiation sickness after y-exposure at a non-lethal dose of 6.7 Gy, which manifested itself in the accelerated formation of endogenous spleen colonies and spleen mass recovery, as well as in the lesser degree of leukopenia on the 12th and the 16th day after acute radiation injury. Quercetin per se did not have a radio-protective effect.

[Nutritional support in the treatment of gastric cancer].

The investigation involved 307 patients operated on for gastric adenocarcinoma. Nutritional support was given enterally (50), parenterally (98) and by standard methods (159). Enteral nutrition should be recommended because it was followed by relatively higher total protein and serum albumin levels.

[Radioprotective properties of a radioprotector of emergency action indraline at its adminisration after irradiation in conditions of local shielding of a rat abdomen].

In experiences on white rats at a gamma-irradiation in a lethal dose LD97/30 in conditions of local schielding of an abdomen (in the field of a liver) and application of a radioprotector indraline after irradiation the expressed efficiency of combined protection up to 87.5% is scored at 31.3% of a survival in local schielding of an abdomen group and absence of effect from a drug.

[The characteristic of radioprotective properties of a radioprotectant B-190 at its administration after radiation].

In experiences on mice F1 (CBAxC57B 1/6) at a gamma-irradiation in a lethal dose LD(35-70/30) the radioprotectant B-190 at administration after an exposure would rise an animal survival--on 35-55%, caused the increase of the amount of endogenic colony in a spleen and of leucocytes in blood on 11th and 30th day of an acute radiation desease accordingly. The drug has the effect in the interval of doses from 75 up to 150 mg/kg b.w. with the rise of radioprotective action on dose reduction factor from 1.1 up to 1.22. alpha(1)-adrenoblockers terasosin in a dose of 15 mg/kg b.w. partially would reduce radioprotective properties of B-190 as radioprotectant or and drug of early therapy of acute radiation desease.

[Comparative effectiveness of antioxidant melatonin and radioprotectors indralin and phenylephrine in local radiation injuries]. / Sravnitel'naia éffektivnost' antioksidanta melatonina i radioprotektorov indralina i mezatona pri mestnykh luchevykh porazheniiakh.

In experiments on mice radioprotective properties of indraline, phenyleprine and melatonin were compared at topical application as an ointment at a place of local exposure of animal hind to a dose of 38.3 Gy of 60Co gamma-quanta. Factor of dose reduction was 1.27-1.32 for indraline (1-10% ointment) and 1.29 for phenyleprine (0.25% ointment). Antioxidants were low efficient at radiation skin burn. At later local radiation injuries, such as hind contracture, the efficiency of indraline was 1.33-1.5, that of phenyleprine was 1.28, and that of melatonine (2 and 5% ointment) was 1.23-1.47.

[The effect of second messengers on neutrophil movement]. / Vliiane vtorichnykh posrednikov na dvigatel'nuiu aktivnost' neitrofilov.

Effects of cAMP and cGMP dibutyryl derivatives (dbt), calcium ionophore A23187 and the protein kinase C activator PMA phorbol ester on mobility of human blood neutrophils were studied using the Magiskan 2A system of image processing. These drugs were added at concentrations, which allowed to produce similar inhibition of the cells mobility using a pattern of the middle velocity measurement in the cell population: dbt cAMP 5.10(-5)M, A23187 10(-6)M, PMA 10(-5)M; dbt cGMP 5.10(-6)M stimulated the neutrophil mobility. Differences in the patterns of mobility inhibition were detected by means of spectral characteristics related to alteration in the area of individual neutrophils. The drugs with inhibitory action (cAMP, A23187 and PMA) caused a decrease in the spectrum capacity of the area alteration as compared with normal state, while they affected dissimilarly the spectrum frequency characteristics. Dbt cAMP did not alter the frequency characteristics, A23187 shifted the spectrum towards a high frequency region and PMA--towards a low frequency range. Dbt cGMP did not alter the spectrum capacity but shifted it slightly to low frequency region. These alterations in the spectrum frequency characteristics are discussed considering the effect of secondary messengers on three types of the neutrophil movement which exhibit inherent frequencies.

[Lipid peroxidation and various parameters of mineral metabolism in patients with alimentary obesity during therapy with monosodium glutamate]. / Issledovanie perekisnogo okisleniia lipidov i nekotorykh pokazatelei mineral'nogo obmena u bol'nykh alimentarnym ozhireniem pri ispol'zovanii v dietoterapii mononatriia glutamata.

Lipid peroxidation and mineral metabolism were studied in patients with III degree of obesity and bad standing of sodium restricted diet before and after treatment with including in diet of monosodium glutamate (MSG). It was established well being of MSG and absence of negative effect on loss of body mass in course of dietary treatment. MSG caused normalization of level of diene conjugates and some minerals in serum of patients.

[Radiation risk in aircraft altitude flights]. / Radiatsionnyi risk pri vysotnykh aviatsionnykh poletakh.

The radiation risk in aircraft altitude flights was evaluated from calculated dose fields at the altitude of 10-30 km 0-90 degrees North modulated by the galactic cosmic radiation (GCR) in quiescent heliophysical periods. Results of dose measurements in flight are discussed in the light of present-day radiation limits. The authors suggest that pilots should be subsumed under the category of professionals who work with sources of ionizing radiation.

Effect of radioprotector Indralin on the course of acute GVH disease.

The effect of radioprotector indralin on the graft-versus-host reaction was studied on the model of acute GVH disease induced in mice by intraperitoneal transplantation of 40x10(6)semiallogenic splenocytes. The effect was evaluated by animal mortality from GVH disease. Recipients were male F1(CBAxC57Bl/6) mice exposed to 7 Gy 24 h before transplantation. Donors were male C57Bl/6 mice. Indralin, intraperitoneally injected in a dose of 100 mg/kg 5 min after irradiation attenuated the severity of GVH disease. It eliminated phase I of acute GVH reaction and shifted to the right the dynamics of mortality. Estimated time of 50% mortality (LT50) was prolonged by more than 4 days (the parameter increased by 31.1%). Two (5.7%) animals recovered from acute GVH disease, while all controls died. Indralin treatment after irradiation resulted in a 30% increase in survival of exposed mice.

[Role of polarization and resonance in assessing the biological effects of electromagnetic radiation]. / Rol' poliarizatsii i rezonansa v otsenke biologicheskikh éffektov élektromagnitnogo izlucheniia.

The dosimetric concept of measurements of electromagnetic radiations (EMR) during irradiation of biological objects can be realized by methods of mathematical modelling of EMR interactions with biological objects, which can be represented as an image of the human body as a uniform ellipsoid of revolution. The efficient surface of EMR absorption for the models shows a marked resonance dependence on the radiation frequency. The ratio of the largest to the smallest axes of the ellipsoid of revolution can be used as a resonance criterion. Besides, radiation polarization needs to be taken into consideration. This paper discusses the frequency dependence of the efficient absorption surface for three major types of radiation polarization. The paper demonstrates an applicability of the calculation method to the evaluation of the EMR absorbed dose rate.

[Kinetics of guinea pig taenia coli smooth muscle relaxation. Effect of papaverine and polarization]. / Kinetika rasslableniia gladkoi myshtsy taenia coli morskoi svinki. Vliianie papaverina i poliarizatsii.

Experiments were conducted on isolated strips of the guinea pig taenia coli by the double sucrose gap technique. The effect of papaverins on the relaxation kinetics of the polarized and depolarized smooth muscle after contractions induced by electric stimulation was investigated. Depolarized muscle was stimulated by long-lasting hyperpolarizing pulses; contraction arose in response to the termination of the current pulse (off-response). It was found that: 1) the relaxation phase of the depolarized muscle off-response was slowed down as compared with the relaxation phase of the spontaneous contractions in Krebs solution; 2) papeverine accelerates the relaxation phase of the off-response of the depolarized muscle; 3) papaverine does not accelerate the relaxation phase of the evoked contractions in Krebs solution; 4) hyperpolarization and additional depolarization accelerate the relaxation phase of the off-response of the depolarized muscle; 5) hyperpolarization does not accelerate the relaxation phase of the off-response of the depolarized papaverine-treated muscle. The data obtained suggest the existence of the slow electroexcitable calcium channels in the membrane of the smooth muscle cells blocked by papaverine. The calcium influx through these channels slows down the relaxation phase of the depolarized muscle off-response.

[A simple method for recording the relative volumetric changes in cells adhering to glass]. / Prostoi metod registratsii otnositel'nykh ob''emnykh izmenenii adgezirovannykh na stekle kletok.

The paper describes a simple method for registering the relative volume changes of the cells adhering to a glass surface. The changes in the luminosity of cells which followed changes in the osmolarity of the medium were registered by means of microscope with a dark-field condenser and the photoelement connected through the DC amplifier to the continuous ink recorder. It was proved that changes in the cells luminosity really represented the relative cell volume changes. The method allows continuous recording of the amplitude and time course of cell volume changes throughout the experiment with many changes of the solution perfusing the cell chamber, which makes it possible to study the effects of pharmacological agents on the mechanisms of cell volume regulation. Provided that the cell membranes are destroyed by detergents the method allows measurement of the activity of the cell contractile apparatus.