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.

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.

[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.

[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.

[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.

[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.

[Role of the functional state of polymorphonuclear leukocytes in the pathogenesis of experimental sepsis]. / Rol' funktsional'nogo sostoianiia polimorfoiadernykh leikotsitov v patogeneze éksperimental'nogo sepsisa.

The functional states of the polynuclear leukocytes examined on the original experimental sepsis model have been studied. It has been shown that the bioactive factors of the microorganisms define the functional states of the polynuclear leukocytes. The features of the different forms of the sepsis are explained with such phenomenon.

[Measuring of intracellular Ca2+ concentration in macrophages. Effects of platelet activation factor]. / Izmerenie vnutrikletochnoi kontsentratsii Ca2+ v makrofagakh, vliianie faktora aktivatsii trombotsitov.

In experiments on mice resident and stimulated thioglycolate macrophages the changes in cytoplasmic Ca2+ concentration Ca2+ have been studied by the use of the fluorescent probe fura-2. PAF acether (10(-7) M) raised Ca2+ by 300-400 nM within 1 min only in the stimulated macrophages. In the resident cells this increase was much less. In the presence of 2mM EGTA, PAF raised Ca2+ to a lesser extent. This suggests that PAF causes influx of exogenous Ca2+ through the receptor-mediated channels as well as releasing Ca2+ from intracellular stores.

[Neutrophil motility in patients with early infection (rapid analysis using automatic image processing system, Magiscan)]. / Podvizhnost' neitrofilov u bol'nykh s ranevoi infektsiei (ékspress-analiz na osnove sistemy obrabotki izobrazhenii Magiskan).

The authors studied the dependence of blood neutrophil motility on the physical state of patients with infected wounds. Neutrophil motility was recorded and analyzed with the help of Magiscan-2a system of automatic image processing. A special software was developed for monitoring the movement of cells and measuring their displacements. Motility of each separate cell and a mean motility of the neutrophil population were determined on the glass in the microscope field (512 x 512 microns). Velocity of each neutrophil was shown to be nonuniform but approximately constant. Cell velocities in each probe were distributed in a continuous manner. Mean velocity of neutrophils in the probe was a stable index of the population motility. Decrease in neutrophil motility in the blood of patients with infected wounds was probably due to the adverse effect of serum factors. The application of the system of image processing makes it possible to carry out express analysis of neutrophil motility to estimate the efficiency of medical treatment.