Antitumor efficacy of extracellular complexes with gadolinium in Binary Radiotherapy.

In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C%=10±3% and leads to complete tumor regression in 25% of mice.

[Increase of X-ray radiotherapy antineoplastic efficacy by use of a gadolinium containing pharmaceutical].

The influence of the gadolinium-containing drug Dipentast (0.5 M water solution of sodium gadopentetate) on the antineoplastic efficacy of X-ray radiotherapy has been studied. Dipentast possesses neither intrinsic antitumor effect, nor tumor-seeking capability. Mice C57Bl/6 with transplanted adenocarcinoma Ca755 were used in the study. The mice were irradiated with an X-ray machine with an anode voltage of 200 kV. The absorbed dose in the tumor after irradiation was 10 Gy for both experimental and control groups. The mice in the experimental group were treated with a single intraperitoneal injection of 0.3 ml of Dipentast. The observation of the tumour growth rate has shown that intraperitoneal administration of Dipentast prior to X-ray irradiation results in a significant tumour growth delay (12 ± 1 days for the experimental group versus 2 ± 1 in the control group), increasing the median life span from 36 ± 1 days in the control group to 43 ± 1 days in the experimental group, and leads to complete disappearance of the tumour in 25 ± 1% of the animals in the experimental group, while in the control group, no tumour regression was observed.

[The distribution of iodine-125 labeled alpha-fetoprotein in the animal organism and its accumulation in the tumor].

The distribution of iodine-125 labeled human alpha-fetoprotein in mice was studied after its intravenous injection. The maximal accumulation of alpha-fetoprotein in different tissues and organs of animals was observed mainly 5 hours after injection. Then the protein was gradually eliminated from the body. In the liver, intestine and blood of intact animals 125I-alpha-fetoprotein persists for at least three days. Accumulation of alpha-fetoprotein in various tissues and organs may determine the different biological effects of this protein. In the mice with transplanted lymphatic leukemia cells P388 the high level of alpha-fetoprotein accumulation was detected in the tumor tissue, reaching 6% of the injected amount per 1 g of tissue. This allows considering the radionuclide-labeled alpha-fetoprotein as a promising medical radionuclide marker for the radiological detection of malignant tumors.

Comparison of BNCT and GdNCT efficacy in treatment of canine cancer.

In this study efficacy of antineoplastic action of gadolinium NCT and boron NCT in cases of canine melanoma and osteosarcoma was compared. Canine spontaneous tumors, such as melanoma and osteosarcoma, have clinical common features with human malignancies, so these tumors in dogs can be considered as clinical model of human melanoma and osteosarcoma. The study has been carried out on 33 dogs with oral cavity melanoma and 9 dogs with osteosarcoma. Dogs with spontaneous melanoma of oral cavity and osteosarcoma of extremities were selected by the results of clinical examination. Irradiation was carried out at the NCT facility of the IRT MEPhI reactor. Neutron irradiation without boron or gadolinium was chosen as a control method to evaluate the efficacy of NCT.

Prompt gamma neutron activation analysis of 10B and Gd in biological samples at the MEPhI reactor.

The purpose of the work was to build a prompt gamma neutron activation analysis (PGNAA) facility at the MEPhI reactor for analyzing the content of various elements for NCT. The facility was implemented on a monochromatic neutron beam. Methods of quantitative (10)B and Gd measurement have been developed for pharmacokinetic studies. The facility is capable of measuring 1 microg of (10)B and 10 microg of Gd in biological samples with an error less than 10%. The detection limit of the facility is 0.3 microg of (10)B and 2 microg of Gd. Neutron flux attenuation within biological tissue samples was estimated and a new system for determining the elemental concentration was suggested.

[Monitoring of anthropologic parameters and of the functional condition in enrollees].

There is an analysis of a monitoring of health parameters in enrollees of a social university. The results confirm the hypothesis on that the health of schoolchildren and students has been changing for the worse. It is proven as necessary to set up, at high schools, systems of health management applicable to students, including health-improving measures for male students, whose health has been declining, according to some parameters, faster than in female students.

The interaction of block copolymers of ethylene oxide and propylene oxide and their polymer-protein conjugates with lipids.

The interaction of block copolymers of ethylene oxide and propylene oxide with lipid structures-monolamellar and multilamellar vesicles from egg yolk lecithin and dipalmitoylphosphatidylcholine-was studied by differential scanning calorimetry, light scattering, and electron spin resonance. Copolymers with different ratios of hydrophilic: hydrophobic portions, numbers of polymers, and arrangements or positions of the blocks, as well as conjugates of polymers with proteins, were used. Peculiarities in the macromolecular structure of the copolymers influence the character of their interactions with lipids. The effects of copolymers which become incorporated into the lipid bilayer are compared with that of polyethyleneglycol which influences lipid structure in an indirect manner.

Treatment of experimental genital herpes with liposomal interferon.

The therapeutic effect of genetically engineered interferon (reaferon) in the treatment of genital herpes in male guinea pigs was studied. The disease was induced in the animals by application of culture liquid containing herpes simplex virus type 2 (HSV-2) to the scarified skin of the penis. The affected sites were treated once daily, for 7 days, with different reaferon preparations 1-3 days after the symptoms of the disease had appeared. Reaferon preparations were most effective in the treatment of experimentally induced genital herpes when incorporated into liposomes, had a less pronounced therapeutic effect when mixed with 3% deoxymethylcellulose to form a hydrocolloid, and were least effective in aqueous solution. Incorporation of the antiviral agents acyclovir and Biolf-62 into liposomes also showed improved effectiveness, in comparison with the free compounds, in the treatment of genital herpes in guinea pigs.

[The pharmacokinetics of recombinant alpha 2-interferon (reaferon)]. / Farmakokinetika rekombinantnogo al'fa 2-interferona (reaferona).

The use of electrochemical iodination under potentiostatic conditions resulted in generating 131I-labeled alpha 2-interferon (IF) the antiviral activity of which differed statistically insignificantly from that of the intact preparation. The resulting radioactive analogue of alpha 2-IF was successfully used for the study of pharmacokinetics of reaferon (RFN) in experimental animals which determined the parameters of the processes of its elimination from the blood stream, accumulation and release from the liver, the organ in which the highest accumulation of alpha 2-IF is observed. It is concluded from the foregoing that it would be expedient to use RFN for treatment of viral disease of the liver and the lungs.

[A radioisotope method for assessing the anaphylactogenicity of polymer drugs]. / Radioizotopnyi metod otsenki anafilaktogennosti polimernykh lekarstvennykh sredstv.

A radioisotope technique has been developed for the quantitative assessment of microcirculation disorder in a local anaphylactic focus of guinea pigs sensitized with horse immunoglobulin G and polyethyleneoxide conjugate with 2,4-dinitrophenol. The technique is based on the use of a radioactive tracer, dextran derivative, labelled with radionuclide 125I. The method can be used for studying a safety of new polymer-containing drugs.

[Pharmacokinetic study of dextran conjugates with catecholamines possessing hypotensive activity]. / Farmakokineticheskoe izuchenie kon''iugatov dekstrana s katekholaminami, obladaiushchikh gipotenzivnoi aktivnost'iu.

The experiments on albino female rats given 125I-labelled conjugates of dextran with noradrenaline and dopamine possessing various hypotensive activity revealed correlation between the hypotensive activity of the conjugates under study and the level of their accumulation in the liver.

[Diagnostic importance of various methods of determining infectious O-antigenemia in patients with typhoid and paratyphoid fevers A and B]. / Diagnosticheskoe znachenie razlichnykh metodov opredeleniia infektsionnoi O-antigenemii u bol'nykh briushnym tifom, paratifami A i B.

Altogether 181 patients with typhoid and paratyphoid fever (54 with typhoid fever, 50 with paratyphoid fever type A, and 77 with paratyphoid fever type B) were investigated. Of them 108 (59.7%) patients were examined during the 1st week of disease. Serum specific O-antigens of typhoid and paratyphoid fever agents were determined by enzyme immunoassay (EIA), radioimmunoassay (RIA), and O-aggregate hemagglutination reaction (O-AHA), serum specific O-antibodies were determined by RDHA, EIA, RIA or O-AHA used during the 1st week of disease were twice as effective as RDHA. Combined use of EIA and O-AHA for the detection of serum specific O-antigens made it possible to diagnose typhoid fever in 90.91%, paratyphoid fever type A in 96.15%, and paratyphoid fever type B in 95.55% of cases.

[Solid-phase method of immunoradiometric determination of the O antigen of Salmonella typhi]. / Tverdofaznyi metod immunoradiometricheskogo opredeleniia O-antigena bakterii briushnogo tifa.

The solid-phase variant of radioimmunoassay for the determination of S. typhi O-antigen has been developed. The sensitivity of this method is 0.1 microgram/ml of the antigen in the blood serum of patients. The study of a number of blood serum samples collected from patients with typhoid fever has confirmed the possibility of using this method in clinical practice.

[Polyethylene oxide-based artificial antigens. An experimental study of the kinetics of the distribution of polyethylene oxide derivatives]. / Iskusstvennye antigeny na osnove polietilenoksida. Eksperimental'noe izuchenie kinetiki raspredeleniia proizvodnykh polietilenoksida.

125I-labeled derivatives of iodaryl-polyethylene oxide with mol. wt. equal to 3 X 10(3), containing and not containing dinitrophenyl (DNP) residues (haptens), were obtained. The capacity for anti-DNP response was shown to be unaffected by the presence of the iodaryl group. The pharmacokinetics of both derivatives of polyethylene oxide were studied in experiments on noninbred white rats receiving these derivatives intravenously in doses of 0.53-0.80 mg/kg. These experiments revealed the following differences in the pharmacokinetics of the derivatives under study: the presence of the DNP group led to an increase in the level of polymer fixation in the body of the animals, particularly in their blood, liver and spleen. Differences in the content of radioactive substances in other organs were not statistically significant.

[Use of the liposomal forms of a terrilytin preparation for the lysis of experimental thrombi]. / Ispol'zovanie liposomal'nykh form preparata terrilitina dlia lizisa éksperimental'nykh trombov.

Thrombolytic activity of liposomal terrilytin forms has been experimentally studied. Liposomal terrilytin form (50-280 PU/kg) was administered to rabbits 24 hours after the experimental induction of femoral thrombi. In 43.75% of cases complete lysis of the thrombi was noted, in 37.5% of cases different stages of the lysis of wall thrombi were observed and in 18.75% of cases the thrombi remained. In the control experiments the thrombi remained in 75% of cases, while in 25% of cases spontaneous lysis of the thrombi occurred. Statistically significant hemostasis changes gave evidence of the decrease in the blood clotting activity after oral administration of a liposomal terrilytin form. It has become possible to achieve thrombolytic effect using lower doses of orally administered liposomal terrilytin form, which is both therapeutically and economically important.

[Isolation and properties of chymotrypsin and trypsin labeled with iodine radioisotopes]. / Poluchenie i svoistva khimotripsina i tripsina, mechennykh radioizotopami ioda.

Comparative study of iodination of chymotrypsin and trypsin was carried out using either iodine monochloride or the electrochemical procedure under conditions of controlled anode potential. It was shown that a part of iodine monochloride was consumed for oxidation of protein molecules. As a result of this process specific activity of the enzymes was decreased down to 50-60% of the initial activity after introduction of 2 atoms of iodine per a molecule. The similar degree of iodination under mild conditions of electrolysis in potentiostatic experiments caused considerably lower decrease in the enzymatic activity, reaching 5-10% of the initial activity (after introduction of I atom of iodine per a molecule--2.5%); labelling of trypsin and chymotrypsin by means of iodine radionuclides is promising for various medico-biological purposes.

[Method for the statistical processing of the results of an immunoenzyme analysis]. / Metod statisticheskoi obrabotki rezul'tatov immunofermentnogo analiza.

A method for the statistical processing of data having different distribution functions is proposed. This method consists in the use of integral distribution functions. The description of the method based on the use of Soviet serial table-top microcomputers, model Elektronika MK-56, with specially developed programs (primary statistical data processing and single-factor regression analysis) is presented. The possibilities of this method are illustrated, by way of example, by processing the results of the determination of Shigella sonnei O-antigen, obtained by ELISA of serum samples taken from patients divided into different clinical groups according to the dynamics of the disease and the therapeutic methods used, as well as from control groups: healthy persons and patients with other intestinal diseases (salmonellosis and Escherichia coli infection). The above procedure has made it possible to differentiate the level of infectious O-antigenemia in accordance with the duration and the severity of the disease, as well as in accordance with the effectiveness of therapy.