Glass transition as a topological phase transition.

The glass transition is described as a phase transition in the system of topologically protected excitations in matter structure. The critical behavior of the system is considered in both static and dynamic cases. It is shown that the proposed model reproduces most of the characteristic thermodynamic and kinetic properties of glass transition: the Vogel-Fulcher-Tammann law, the behavior of susceptibility and nonlinear susceptibilities, and heat capacity behavior as well as the appearance of a boson peak in the frequency dependence of the dynamic structure factor near the glass transition temperature.

Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin.

We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBA×C57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an α1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound. Monizol administered prior to indralin eliminated radioprotector-induced hypertensive reaction, reduced bradycardia by more than 2 times, and attenuated the effect of indralin on spleen weight and blood loss from the wound by 1.6-1.8 times. Monizol administered after indralin had no effect on shifts in peripheral blood supply caused by the radioprotector.

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.

Radioprotector indralin at early and late manifestations of local radiation injuries.

Experimental model of acute local radiation injuries (LRI) was the degree of radiation skin burns of mouse paws, observed through the 10 day within 1 month after local γ -60Co-irradiation at the doses of 20-45 Gy. For late local radiation injuries with a maximum of over 6 months after exposure to radiation, model was the contracture of animal paws and post-radiation amputation of limbs of the mouse. In the experiments on mice radioprotector indralin (B-190) IP as direct α1-adrenomimetic has a expressed protective effect on reducing acute and late LRI, equal in terms of dose reduction factor (DRF) 1.4 -1.5 that was comparable to their efficacy during radiation injuries of hematopoietic tissues. Indralin fully retain its radioprotective properties (DRF = 1.5-1.7) in the condition of repeated radioprotector administration through one day at total dose of 57 Gy (three times 19 Gy) of fractionated γ -irradiation. The protective effect of indralin improved at parenteral administration in the place of local irradiation. The local topical application of indralin in the ointments or in solution of dimethylsulfoxide has radioprotective effect, equal in the term of DRF to 1.3 -1.5 at acute and late LRI. Indralin also possessed a expressed radioprotective properties (DRF = 1.5) in decrease radiation injuries of salivary glands during local irradiation of head of rats.

Quantum-to-classical crossover near quantum critical point.

A quantum phase transition (QPT) is an inherently dynamic phenomenon. However, while non-dissipative quantum dynamics is described in detail, the question, that is not thoroughly understood is how the omnipresent dissipative processes enter the critical dynamics near a quantum critical point (QCP). Here we report a general approach enabling inclusion of both adiabatic and dissipative processes into the critical dynamics on the same footing. We reveal three distinct critical modes, the adiabatic quantum mode (AQM), the dissipative classical mode [classical critical dynamics mode (CCDM)], and the dissipative quantum critical mode (DQCM). We find that as a result of the transition from the regime dominated by thermal fluctuations to that governed by the quantum ones, the system acquires effective dimension d + zΛ(T), where z is the dynamical exponent, and temperature-depending parameter Λ(T) ∈ [0, 1] decreases with the temperature such that Λ(T = 0) = 1 and Λ(T → ∞) = 0. Our findings lead to a unified picture of quantum critical phenomena including both dissipation- and dissipationless quantum dynamic effects and offer a quantitative description of the quantum-to-classical crossover.

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.

Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors.

Involvement of hormonal response (catecholamine release) to acute hypoxia induced by radioprotectors in modification of their radioprotective properties was studied in experiments on outbred mature female albino mice, female albino rats, and dogs of both sexes. The response intensity was evaluated by the reduction of radioprotective and toxic properties of indralin (a α1-adrenoceptor agonist and a radioprotector). The radioprotective effect of indralin was measured using lethal doses of whole-body γ-irradiation ((60)Co) and its acute toxicity was assessed by LD50. It was found that repeated administration of indralin with 30-60-min intervals was followed by weakening of its radioprotective effect. Similar sensitization effect of indralin was observed after pretreatment with cystamine and epinephrine. Comparison of the severity of sensitization after administration of epinephrine and cystamine in the dose providing radioprotective effect showed that the potential aminothiol-induced release of catecholamines can provide optimal long-term radioprotective effect of epinephrine.

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.

Effect of α1-adrenomimetic indralin on oxygen consumption by bone marrow cells in vitro.

In vitro experiments with excessive and normal oxygenation of the culture medium showed unchanged oxygen consumption by mouse bone marrow cells under the influence of radioprotector indralin belonging to α1-adrenomimetics (100 µg/ml). After exhaustion of oxygen in the medium below 10 µM and progressive decrease in cellular respiration, indralin stimulated oxygen consumption by bone marrow cells by 1.5 times. The role of the observed effect of indralin in the realization of its radioprotective properties is discussed.

[Combined effect of quercetin and indralin (B-190) in alleviating carboplatin hematologic toxicity].

In experiment conducted on male mice of C57B1/6 line quercetin (80-100 mg/kg injected 60 minutes before carboplatin) or an emergency radioprotector indralin B-190 (50-100 mg/kg injected 5 minutes after carboplatin) decreased the mortality of animals from toxic carboplatin dose of 100 mg/kg from 40% to 10-11% (p < 0.05). In mice receiving both quercetin and B-190 the reduction of carboplatin toxicity evaluated by blood WBC level was even more prominent (p < 0.05). The results were confirmed in rat experiment. In animals receiving both quercetin and B-190 with 50 mg/kg of carboplatin the WBC level was higher (p < 0.05). Quercetin alone had no effect on hematologic toxicity in those settings. Besides, quercetin and B-190 didn't have any effect on RBC level changes.

[Radiation protectors within the radiation safety system for extended duration exploration missions].

Radiation environment in extended duration exploration missions is scrutinized in the context of the probability of the risks of deterministic and stochastic effects of radiation. Though the probability of severe radiation damage due to solar flare is very low, nonetheless it is requisite that the crew must be provided with appropriate, including pharmacological safeguards. The current nomenclature of radiation protectors composes short-term agents against acute radiation damage. Among the others, preparation B-190 is distinguished by particularly high effectiveness and universal action, and good tolerance even when organism is exposed to the extreme factors of space flight Regimen of B-290 therapy alone and with combination with aminothiol preparations have been developed to render treatment following multiple solar events. Effectiveness of radioprotectors can be increased substantially by local shielding of the abdomen and pelvis. The most promising nonspecific stimulators of total resistance of organism are riboxin (inosin) and combined preparation aminotetravit as well as vitamins tocopherol and retinol. Therapy combining B-190 with riboxin and aminotetravit is also under discussion. Cytokine neipogen is also viewed as a candidate agent for early therapy. Concern is raised about possible development of chronic oxidative stress in long-duration exploration missions. Highlighted is the significance of adequate nutrition supplemented with fresh vegetables as a source of the most valuable bioflavonoids. Antioxidants L-selenomethionine and melatonin proved their effectiveness against heavy nuclei of galactic radiation. An open issue is how to make natural antioxidants beneficial to oxidative stress control and attenuation of low-intensity galactic radiation.

[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.

[Indralin--a novel effective radioprotector during irradiation by high-energy protons].

Experiments with 120 mongrel dogs were aimed at the assessment of radio protective strength of indralin and local shielding of the pelvic marrow from 2.5 Gy, and also their concurrent use for the dogs irradiated by protons (240 MeV) at absolutely lethal and over-lethal 4 Gy and 5 Gy. Clinical observations, hematological investigations and ECG analysis of survived animals were conducted 4.5 years post the irradiation. Dogs that remained healthy following 3.5 to 4.5 years since the irradiation were sacrificed for pathomorphological investigations. The radioprotective effect of local shielding against 4 Gy was weak while this effect of intramuscular indralin (10, 20, 40 mg/kg of body) was significant reaching 50 to 67.7%. The concurrent use of two methods had, apparently, potentiated the 100% radioprotection of the animals irradiated by overlethal 5 Gy. Blood investigations of the survived dogs every 2-4 months evidenced that complete recovery of the total leukocyte count had taken 9 to 13 months. Also, dogs' pregnancy in 9-10 months since the beginning of irradiation pointed to maintenance of fertility and the ability to parturiate 2 or 3 times yielding 5-6 live cubs. Necropsy of the dogs did not reveal gross macroscopic structural changes of visceral organs or tissues. Seven out of 27 sacrificed dogs had benign tumors infrequent in intact dogs at this age.

[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.

Effect of radioprotector indralin on carboplatinum hemotoxicity.

A decrease in carboplatinum hemotoxicity was detected in experiments on C57B1 mice treated with the drug in combination with indralin (urgent radioprotector). Carboplatinum in a dose of 125 mg/kg, injected intraperitoneally, caused 80-100% death; the median term of death was 6 days (3-17). Single oral dose of indralin (100 mg/kg) during the 1st min or 15 min after carboplatinum injection (125 mg/kg) increased animal survival by 40.0-46.7% by day 20 of the experiment primarily during the period of manifest hemotoxicity (days 7-17), indralin injected 1, 2, or 4 h after carboplatinum exhibited no chemoprotective effect.

Effect of melatonin, ascorbic acid, and succinic acid on the cumulative toxic effect of repeated treatment with gammafos (amifostine).

Daily treatment of outbred albino mice with gammafos in radioprotective doses of 300 and 500 mg/kg for 4 days produced a cumulative toxic effect. This effect was not observed after decreasing the dose of gammafos to 100 mg/kg. Repeated peroral administration of melatonin and ascorbic acid in a dose of 200 mg/kg 30 min before treatment with gammafos reduced its cumulative toxic effect. Succinic acid in a dose of 100 mg/kg was ineffective under these conditions. The cumulative death time for 50% animals receiving gammafos alone or in combination with melatonin, ascorbic acid, and succinic acid was 3.08, 4.29, 4.06, and 2.97 days, respectively.

[Radioprotective capacity of indralin in reducing radiation injury to salivary glands]. / Protivoluchevye svoistva indralina po snizheniiu tiazhesti luchevogo porazheniia sliunnykh zhelez.

Radioprotective capacity of radioprotector indraline (alpha-1(B)-adrenoagonist) was studied by its effect on early displays of a local radiation injury to salivary glands in white rats after X-ray irradiation of an animal head with a dose of 18.7 Gy. Indraline was found to be capable to reduce a radiation injury to parotid glands registered by reduction of gland mass on 6th day after irradiation. In experiments on rats, radioprotective efficiency of indraline (100 mg/kg) in term of DRF is close to 1.5.