Evaluation of Antitumor Efficiency of High Intensity Radiation 169Yb Source on Experimental Sarcoma M-1.

Rats with sarcoma M-1 were exposed to high dose rate irradiation with 169Yb source. In 25 days after introduction of a trocar with sealed capsule with 169Yb source into the tumor, complete tumor regression was observed in 70% animals. The results suggest feasibility of using 169Yb source for high-dose rate brachytherapy and development of the personalized medicine approaches.

[Radioprotective Properties of NO-synthase Inhibitor T1023: II. The Ability for Selective Protection of Normal Tissues During Radiotherapy of Tumors].

We studied the effect of T1023, NO-synthase inhibitor, N-acyl-S-alkyl-isothiourea in a single administration at a dose of 75 mg/kg on the growth of transplantable rat sarcoma M-1 and the development of acute skin reactions after the local impact of γ-radiation at the doses of 32 and 36 Gy. The results showed that the T1023 at a single dose had no effect on the growth of sarcoma, and did not modify the radiosensitivity of the tumor and anti-tumor efficacy of γ-rays. However, at both doses T1023 significantly reduced the severity of acute radiation skin reactions. NOS inhibitor did not change the duration of the inflammatory and regenerative processes, but significantly limited the degree of radiation alteration of the deep layers of the skin and underlying tissues. The findings suggest that the hypoxic mechanism of antitumor action allows T1023 to selectively protect the non-malignant tissue during radiation therapy of solid tumors. Therefore, this compound may be regarded as a promising basis for the development of pharmacological prevention of radiotherapy complications.

[The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].

The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

[Growth kinetics and functional morphology of M-1 sarcoma in rats before and after gamma-irradiation]. / Kinetika rosta i funktsional'naia morfologiia sarkomy M-1 u intaktnykh krys i posle gamma-oblucheniia.

The study was concerned with growth of sarcoma M-1 and basic morphological characteristics of proliferative activity of cells of this strain as well as apoptosis of cells at different stages of tumor progression in rats before and after a single gamma irradiation at 30 Gy. At the parenchymal periphery which determines tumor growth, the PCNA index of proliferating cells was 76.5%; spontaneous cell death--0.28%. During post-irradiation period, the sarcoma PCNA index fell to 62.3% while the apoptotic index rose five-fold. These findings support the concept of radiation-induced apoptosis being a major pathogenetic factor responsible for effectiveness of radiotherapy of tumors. Indirect evidence on PCNA immunostaining suggested that synthesis of this cyclin is sensitive to the level of oxygen input in the cell, yet it offers sufficient resistance to gamma-radiation.

[The survival of mice and the metallothionein content of their livers and kidneys as criteria for assessing exposure to pulsed neutron radiation]. / Vyzhivaemost' myshei i soderzhanie metallotioneinov v ikh pecheni i pochkakh kak kriterii otsenki vozdeistviia impul'snogo neitronnogo izlucheniia.

The effect of pulsed neutron radiation was studied in comparison with continuous neutron radiation and continuous gamma-radiation. Animal survival and induction of metallothionein (MT) synthesis in liver and kidney of mice exposed to equivalent doses were chosen as criteria for evaluation of radiation effects. It was found that the level of MT in liver and kidney of mice exposed to neutron radiation decreased 24 hours after irradiation and then continued decreasing in kidney for 48 hours after irradiation. This is evidence of more intensive free-radical processes initiated by pulsed neutron radiation. At the same time, RBE values of pulsed neutrons did not differ significantly from that of continuous neutron radiation.

Some biological mechanisms of the inborn predisposition to alcoholism.

The children of alcoholism patients have a high biological risk of this illness, mental and emotional disorders, and behavioral disturbances. The offspring of white mongrel rats with chronic alcohol intoxication were investigated in order to study the neurochemical mechanisms of these phenomena. The content of DA in blood and blood plasma, the characteristics of GABA and the opiate receptors of the brain, the activity of DBH, COMT, MAO, the content of cAMP and cGMP in brain tissue, as well as the expression of the gene c-fos were studied. Changes in the brain content of DA and qualitative and quantitative changes in MAO (an increase and solubilization of MAO A and B activity in the liver) were identified in the offspring of alcoholic rats. A tendency was also observed in the brain toward a decrease in the activity of DBH and COMT and an increase in the activity of cAMP and cGMP. The baseline expression of the gene c-fos in the offspring of male alcoholic rats did not differ from the norm; however, a powerful increase in the expression of the gene c-fos did appear in response to the administration of 2 g/kg of ethanol, in the absence of this effect in the control. A view is presented on the significant role of changes in the functions of the DA system in the genesis of pathology in the offspring of parents with chronic alcohol intoxication, as well as on the possible influence of the prolonged consumption of alcohol on the function of the genome.

[Effect of active immunization with dopamine- and norepinephrine-protein conjugated on neurochemical and neurophysiologic parameters of withdrawal syndrome in chronically morphine-treated rats]. / Vliianie aktivnoi immunizatsii kon"iugatami dofamina i noradrenalina s belkom na neirokhimicheskie i neirofiziologicheskie pokazateli sindroma otmeny u khronicheski morfinizirovannykh krys.

The impact of induction of antibodies to the catecholamines (CA) dopamine (DA) and norepinephrine (NE) during active immunization of rats with CA conjugated to protein (BSA) on morphine dependence, withdrawal syndrome, and neurotransmitter status was studied during 14-day morphine treatment. DA-BSA and NE-BSA immunization of rats provided lower plasma DA concentrations in naloxone-precipitated opiate withdrawal. However, it failed to lead to normalization of hypothalamic DA levels and exacerbated the withdrawal syndrome. In immunized rats, including those immunized with BSA, the hypothalamic levels of DA and epinephrine (E) were even higher than in morphine-treated rats previously unimmunized. The aggravation of withdrawal symptoms was especially pronounced in rats preimmunized with NE-BSA, which could be due to a significant NE rise in the brain tissue.

[The biological mechanisms of a congenital predisposition to alcoholism]. / Nekotorye biologicheskie mekhanizmy vrozhdennoi predraspolozhennosti k alkogolizmu.

In descendants of white rats with chronic alcoholic intoxication, the contents of DA in the brain and blood plasma, characteristics of GABA and opiate brain receptors, the contents of cAMP and other substances were studied as well as the c-fos gene expression. The data obtained suggest a considerable role of the changes in the DA system functions in the genesis of pathology in these descendants.

[Complex drug therapy of patients with juvenile uterine hemorrhage dependent on the status of the hemostasis system]. / Kompleksnaia medikamentoznaia terapiia bol'nykh s iuvenil'nymi matochnymi krovotecheniiami v zavisimosti ot sostoianiia sistemy gemostaza.

The authors analyze the results of examinations and treatment of 125 patients, suffering from juvenile uterine bleedings, divided into three age groups and subgroups with different status of the hemostasis. They consider the suggested complex of drug therapy as an additional diagnostic test for the detection of the underlying pathogenetic component of such bleedings and recommend a pathogenetically-based hemostasis and adequate therapy to regulate menstrual function.

[Acute skin reactions in rats after irradiation with reactor neutrons]. / Ostrye reaktsii kozhi krys posle oblucheniia reaktornymi neitronami.

The paper is devoted to a study of acute radiation reactions of the depilated thigh skin of outbred rats after their irradiation at various doses with gamma quanta and neutrons of a BR-10 reactor with the mean energy of 0.85 MeV. A scale, developed for the assessment of a degree of severity of radiation reactions permitted quantitative interpretation of the obtained results. The RBE of neutron irradiation was 4.2.

[Diagnosis, therapy and echographic monitoring of the treatment of girls with juvenile uterine bleeding]. / Diagnostika, lechenie i ékhograficheskii kontrol' za lecheniem devushek s iuvenal'nymi matochnymi krovotecheniiami.

The study group included 49 patients aged 16 to 19 years with combined hemostatic and reproductive disorders (n = 26) and reproductive disease without hemostatic defects (n = 23). The study yielded a differential diagnostic protocol for juvenile uterine bleedings, pathogenetically relevant therapy and echographic monitoring of its efficacy.

[RBE of neutrons from the BR-10 reactor based on their antitumor effect and on acute radiation reactions of the skin]. / OBE neitronov reaktora BR-10 po protivoopukholevomu éffektu i ostrym luchevym reaktsiiam kozhi.

The paper is concerned with the results of investigation of antitumor effectiveness (rats, sarcoma M-1) of neutron radiation of a BR-10 reactor with the mean energy of 0.85 MeV, correlated with the effect of 60Co gamma radiation (Luch-1). RBE in single local tumor radiation with neutrons was 4.5, being higher than RBE based on acute skin radiation reactions over a tumor (4.0). For this case FTA is over I (1.13) but slightly lower than after dose fractionated irradiation (1.18). Experimental data indicate the necessity of extending the clinical use of reactor neutrons and a profound study of the effects after neutron irradiation, particularly in dose-fractionated regimens.

[The role of environmental and genetic factors in the development of pathology of the reproductive system in girls]. / Rol' sredovykh i geneticheskikh faktorov v formirovanii patologii stanovleniia reproduktivnoi sistemy u devochek.

Genetic and environmental effects on reproductive development of girls are described. Possible genetic involvement is postulated in girls with opsomenorrhea, second-degree amenorrhea and juvenile bleedings. Abnormal development of the menstrual function is more commonly associated with chronic tonsillitis, stress or weight loss. Environmental effects are particularly frequent and pronounced one year before or during the menarche. Central menstrual disorders were associated with parental reproductive disorders in 47% of the cases.