Blastomogenic activity of p-hydroxyphenyllactic acid in mice.

Blastomogenic activity of p-hydroxyphenyllactic acid was established by prolonged s.c. administration into C57BL/6 and CC57BR mice. Phenyllactic acid was also tested and was not blastomogenic under the same conditions. The preparations in aqueous solutions were injected into the dorsal region twice weekly in 1.5-mg doses. The total dose per mouse was 42 mg p-hydroxyphenyllactic acid or 50 mg phenyllactic acid. The resorptive character and many forms of blastomogenic activity of p-hydroxphenyllactic acid were shown. It induced neoplasms of varied histogenesis (leukemias, adenomas, hepatomas, and tumors of the vascular tissue),including benign and malignant tumors and precancerous conditions of the urniary bladder.

Monolayers of a novel ionoselective butadienyl dye.

The novel amphiphilic benzodithia-18-crown-6 butadienyl dye (1) forms relatively stable insoluble monolayers on distilled water (collapse pressure of 41 mN/m) and on aqueous subphases containing alkali metal or heavy metal salts (collapse pressures in the range of 27-38 mN/m, respectively). The dye 1 monolayer organization depends on chromophore association and interactions (especially complex formation) with heavy and alkali metal ions as deduced from surface pressure-area and surface potential-area isotherms as well as reflection spectra and Brewster angle microscopy observations. Dye 1 undergoes specific interactions with Hg(2+) and Ag(+), respectively (formation of different complexes). Nonspecific interactions have been observed with other salts, such as KClO(4) or Pb(ClO(4))(2). Further, dye 1 monolayers on 1 mM Hg(ClO(4))(2) solution undergo reversible photoisomerization, in contrast to monolayers on water and other aqueous salt subphases.

[Carcinogenic action of 5-methoxytryptamine related to its transformation into 5-methoxyindolyl-3-acetic acid]. / Kantserogennoe deistvie 5-metoksitriptamina, sviazannoe s ego prevrashcheniem v 5-metoksiindolil-3-uksusnuiu kisloty.

A considerable blastomogenic effect of metabolite serotonin 5-methoxytryptamine (5-MOT) subcutaneously administered for a long time to C57BL/6 mice was established. This effect was decreased noticeably if the further metabolism of 5-MOT into 5-methoxyindolyl-3-acetic acid (5-MIAA) was blocked by pyrazidol. These results explain the fact that the blastomogenic effect of 5-MOT is not direct but is caused by the transformation of 5-MOT into its final carcinogenic metabolite 5-MIAA.

[Synthesis of amphiphilic photochromic benzo-15(18)-crown-5(6)-ethers and their properties in monolayers]. / Sintez amfifil'nykh fotokhromnykh benzo-15(18)-kraun-5(6)-éfirov i ikh issledovaniie v monosloiakh.

New amphiphilic photochromic benzo-15(18)-crown-5(6) ethers (APC) differing in the position of the octadecyl substituent and the size of the crown cavity were synthesized. The compounds form stable monolayers in the air/water and air/alkaline metal salt solution interfaces. The results of the pressure isotherm measurements, atomic force microscopy (AFM), and electronic spectroscopy show that the structure of the monolayers formed depends on the structure of the parent APC and the nature of the cation in salt solutions. The area per molecule of APC in the monolayer (specific area) is the smallest on the water surface and increases by 20-40% on the aqueous subphase surface with an increasing concentration of salts therein to indicate the formation of APC complexes with the metal cations. When the hydrophobic aliphatic substituent is displaced from position 3 to position 5 of the benzothiazole ring, the specific area on the surface of water and subphases decreases twofold, which indicates the compactization of the monolayer on this modification. A reversible E-Z-photoisomerization of APC was found in the monolayers formed in the salt solution/air interface. The features of the reaction are defined by the specific organization of the amphiphilic molecules in the monolayer and by the nature of the cation.

[Production of recombinant fragments of the Clostridium tetani neurotoxin for the development of new immune-prophylaxis preparations against tetanus]. / Poluchenie rekombinantnykh fragmentov neirotoksina Clostridium tetani dlia razrabotki novykh sredstv immunoprofilaktiki stolbniaka.

Tetanus belongs to dangerous infection diseases, whose effective prevention can be ensured by vaccines. The acting substance of tetanus vaccines, presently in use, is a partially purified and deprived-of-lethal-action Clostridium tetani neurotoxin. The construction of a subunit preparation on the basis of toxin fragments obtained through gene engineering could be a method aimed at promoting the quality of the used tetanus vaccines. With this goal in mind, we built, within the present case study, the expressing genetic constructions and obtained, in the pure form, an extensive tetanus-vaccine chain with its C-terminal (Hc) fragment, hydride peptides, containing the Hc-fragment and C-terminal fragment of toxin B C. difficile, as well as Hc-fragment and S3 collagen-binding domain of collagenase C. histolyticum. The thus obtained proteins can be used in testing their immunogenic and protective properties, while the conducted study could be a basis for further research of a new-generation vaccine against tetanus and other human infection diseases.

[Experience with the abolition of use of tetanus antiserum following trauma]. / Opyt otmeny primeneniia protivostolbniachnoi syvorotki pri travmakh

For the first time in the USSR, as a result of all-around analysis of the problems connected with tetanus prophylaxis under conditions of the Arkhangelsk region the authors conducted a trial on the suspension of the use of antitetanus serum in trauma. Besides the elimination of the population allergization, replacement of the antitetanus serum with the toxioid facilitated the emergency prophylaxis of tetanus, created prerequisites for the immunity maintenance at the protective level in the population, and served as the necessary stage along the route of further improvement of emergency prophylaxis and elimination of tetanus.

[Use of a synthetic medium for cultivating pathogenic anaerobes]. / Primenenie sinteticheskoi sredy dlia kul'tivirovaniia patogennykh anaerobov

It was shown that a synthetic medium suggested by the authors earlier was useful for the growth and toxin formation of Cl. tetani, Cl. botulinum and Cl. perfringens, types B and E. A study of the character of growth and toxinogensis, microscopic examination of morphology of culture cells and results of passages showed the suggested synthetic medium to be of value; a possibility of its application for studying the nutrient requirements and the role of individual components of the nutrient media in the process of growth and toxinogenesis was also demonstrated.

[The isolation of the ribosomal fraction of Clostridium perfringens type A and an evaluation of its protective activity]. / Poluchenie ribosomal'noi fraktsii Clostridium perfringens tipa A i otsenka ee protektivnoi aktivnosti.

A method for isolation of the ribosomal fraction (RF) from the cytoplasm of type-A C. perfringens strain BP6K was developed and its chemical and antigenic properties characterized. RF has been found to possess protective properties: two subcutaneous immunizations of mice with RF preparations adsorbed on Al(OH)3 in doses of 250 and 500 micrograms (dry weight) has ensured, on the average, the protection of 41.9% of the immunized animals from 1 DCL of type-A C. perfringens strain BP6K culture.

[The expediency and feasibility of abolishing the use of antitetanus serum for injuries in the Arkhangel'sk region]. / O tselesoobraznosti i vozmozhnosti otmeny vvedeniia protivostolbniachnoi syvorotki pri travmakh v Arkhangel'skoi oblasti

The use of antitetanus serum (ATS) in the north taiga soil-vegetative zone and farther to the north is inexpedient because of an insignificant contamination of soil with B. tetani and a trivial contact of the population with soil. In the Arkhangelsk region with a high incidence of trauma and a low tetanus morbidity the damage caused to the population by the administration of ATS in the form of serum sickness (1.1% of the persons given ATS injections) and anaphylactic shock considerably exceeded the value of negative results of the infection. In the presence of immune population (over 86% of the children and 82% of adults are immune) and with additional vaccination of definite groups it is not only possible, but necessary to suspend ATS injections in trauma; instead, 0.5 ml of tetanus toxoid should be used for revaccination. Suspension of ATS application in trauma gives marked economy of the budget of the public health of the region.

[The experimental validation of methods for the emergency immunoprophylaxis of gas gangrene]. / Eksperimental'noe obosnovanie metodov ékstrennoi immunoprofilaktiki gazovoi gangreny.

The effectiveness, both immunological (by an increase in the titers of antitoxins) and protective (by resistance to the inoculation of the absolute lethal dose of infective agents), of the regional (wound) revaccination with tetratoxoid (Clostridium perfringens, C. oedematiens, C. septicum, C. histolyticum) was demonstrated on the experimental model of wound infection (gas gangrene) of guinea pigs. The schedule of rapid immunization with tetratoxoid was developed, which made it possible to create good immunological preparedness (basic immunity) for subsequent revaccination in case of traumas within 6 days. The effectiveness of rapid immunization by the application of tetratoxoid on the wound was shown. This immunization ensured a considered increase in the titers of antitoxins within the first 6 days, which increased the protection of the animals from infection with each of the four causative agents of gas gangrene.

[Immunomorphologic aspects of local (wound) revaccination with tetanus anatoxin]. / Immunomorfologicheskie aspekty mestnoi (ranevoi) revaktsinatsii stolbniachnym anatoksinom.

The immunomorphological reaction of regional lymphoid organs, the pathomorphology of wound tissues, humoral antitoxic response and a protective effect after local (wound) booster immunization with tetanus toxoid have been studied in observations on 100 guinea pigs with experimental wound infection. The study has shown that the local application of tetanus toxoid, besides stimulating humoral response, induces a more rapid effect aimed at the primary elements of the infectious process (the germination of spores, the adhesion, colonization and toxin formation of the causative agent), thus facilitating the localization of the focus of infection, the development of reparative processes in the wound and the arresting of the infection.

[Morphological and histochemical study of the action of a native Clostridium perfringens type A enterotoxin on a model of the ligated ileal loop in the rabbit]. / Morfologicheskoe i gistokhimicheskoe izuchenie deistviia nativnogo énterotokisnia Clostridium perfringens tipa A na modeli pereviazannoi petli podvzdoshnoi kishki krolika.

Morphological studies carried out in the igated loop of the rabbit small intestine, used as a model, have revealed that the action of the enterotoxins of C. perfringens type A reference strain and C. perfringens type A strains isolated in the USSR on the intestinal mucosa is absolutely identical. This action is manifested by the destruction of epithelial cells on the tops of the villi, inflammatory infiltration and considerable exudation of fluid into the lumen of the intestinal loop. Early lesions of the brush border of enterocytes, accompanied by the loss of alkaline phosphatase activity and the disappearance of the glycocalix, have-been histochemically established. C. perfrinegens antienterotoxic serum has proved to be capable of completely neutralizing the histopathological activity of C. perfringens enterotoxin.

[Method of obtaining an erythrocyte diagnosticum for detecting Cl. perfringens type A enterotoxin]. / Metod polucheniia éritrotsitarnogo diagnostikuma dlia obnaruzheniia énterotoksina Cl. perfringens tipa A.

Erythrocytic immunoglobulin diagnostic reagent for detecting Cl. perfringens enterotoxin in the indirect hemagglutination test has been obtained. The diagnostic reagent has been prepared on the basis of antibodies of Cl. perfringens enterotoxin with the use of acroleinized tanned sheep red blood cells. The indirect hemagglutination test with this reagent is characterized by high specificity and sensitivity (the method permits to detect enterotoxin protein at a concentration of up to 0.005 microgram/ml). The preparation thus obtained is stable and ensures highly reproducible results.

[Immunogenic properties of Clostridium perfringens type A anatheta-hemolysin]. / Izuchenie immunogennykh svoistv anateta-gemolizina Clostridium perfringens tipa A.

Guinea-pigs were immunized with anatheta-hemolysin preparations adsorbed on aluminum hydroxide, as well as with the mixture of anatheta-hemolysin and type A Cl. perfringens toxoid, purified and concentrated. Anatheta hemolysin preparations were obtained with the use of homogeneous theta hemolysin, as well theta hemolysin of various purification degrees. As a result, antatheta hemolytic guinea-pig sera capable of neutralizing 2,000-8,000 HU of theta-hemolysin were obtained. Tests made to establish the degree of protection in the immunized guinea-pigs did not show that the animals immunized with the mixture of anatheta-hemolysin and type A Cl. perfringens toxoid, purified and concentrated, had any advantages in the degree of protection over the animals immunized with the toxoid alone. But there is no doubt that this component plays a positive role under the conditions of natural gas gangrene when the hemolytic action of Cl. perfringens toxin becomes considerably pronounced.

[Antigenic interrelations within the species Clostridium novyi, C. histolyticum and C. septicum as a basis for developing an immunofluorescence method]. / Antigennye vzaimootnosheniia vnutri vidov Clostridium novyi, C. histolyticum, C. septicum kak osnova razrabotki immunofliuorestsentnogo metoda.

The cellular and antigenic interrelations within each Clostridium species have been studied with a view to the selection of strains for the preparation of specific rabbit antisera possessing a wide serological spectrum of action within the species. The indirect immunofluorescence test making it possible to determine the species of clostridia in native pathological material from wounds or in cultures, subjected to short-term incubation, within 1-1.5 hours has been developed. This test can be used in laboratory practice for the diagnosis of gas gangrene in humans, as well as for the identification of pathogenic clostridia.

[Improving tetanus prevention in the Krasnodar area taking the current epidemic situation into account]. / Usovershenstvovanie profilaktiki stolbniaka v Krasnodarskom krae s uchetom sovremennoi épidemicheskoi situatsii.

An increase of percentage of elderly persons among those who fell ill with tetanus (70%) was noted against a sharp reduction of tetanus incidence under the effect of mass active immunization against this disease. A study of immunity in older and elderly individuals showed the percentage of immune persons among them to be rather low (48.8--55.6%). Due to difficulty of elderly individuals embracement by vaccination the authors suggest a single immunization scheme with a double toxoid dose (20 BU) followed by revaccination with 10 BU in one year. A total of 21 472 persons were placed under observation. The suggested immunization scheme was harmless, promoted stimulation of antitetanus immunity in persons vaccinated earlier; as to unvaccinated persons--it created a favourable immunological preparedness for revaccination, permitting to do without any antitetanus serum in case of trauma.

[Preparation of diagnostic antitoxic serum to Clostridium difficile]. / Poluchenie diagnosticheskoi antitoksicheskoi syvorotki k Clostridium difficile.

The results of the studies on the preparation of diagnostic antitoxic sera to C. difficile, intended for use in biological assays with the aim of the laboratory diagnosis of clostridial enteric infections, are presented. The conditions for the detoxification of C. difficile native toxin have been established, the optimum schedules for the immunization of rabbits have been selected and specific antitoxic sera to C. difficile have been obtained. The neutralizing activity of these sera has been evaluated in the lethality test and in the cytotoxic test on human embryo dermo-muscular fibroblast cells M-19.

[Effect of regional (wound) revaccination with tetanus anatoxin on the functional activity of immunocompetent cells in the region]. / Vliianie regionarnoi (ranevoi) revaktsinatsii stolbniachnym anatoksinom na funktsional'nuiu aktivnost' immunokompetentnykh kletok regiona.

The study made with the use of complex methods established that the local (wound) application of tetanus toxoid rapidly made the manifestation of the lysosomal apparatus more pronounced, increased the oxidizing activity (determined in the nitro blue tetrazolium test) and phagocytic activity of the mononuclear phagocytizing system in the wound and in the regional lymph nodes. The wound application of tetanus toxoid significantly increased blast transformation of T lymphocytes in guinea pigs simultaneously with tetanus wound infection. The study confirmed the pathogenetic expediency of the proposed method for the stimulation of anti-tetanus immunity by the application of tetanus toxoid on the wound which specifically inhibited the primary stage of the infectious process.

[Morphologic changes in the urinary bladder of mice induced by metabolites of tryptophan and tyrosine]. / Morfologicheskie izmeneniia mochevogo puzyria u myshei, vyzvannye metabolitami triptofana i tirozina

45-day-old 229 mice of lines C57Bl and CC57Br were injected subcutaneously water solutions of tryptophan and thyrosine metabolites 2.5 mg twice a week, the total dosage being 45-50 mg per mouse. For the control mice of the same line were taken. Within the period from 3.5 to 19 months following injection of the metabolites in the urinary bladder of animals, there were observed focal proliferates of the epithelium not infrequently with its atypism, and also lymphoid infiltration of submucous and muscle layers, reticulosarcomas, papillomas, precancerous conditions and cancer. The question of the importance of endogenous blastomogenic substances in the development of "spontaneous" tumors of the urinary bladder in man is discussed.

[Inhibiting effect of domestic, synthetic beta-carotene and ascorbic acid on endogenous carcinogenesis in mice]. / Ingibiruiushchee vliianie otechestvennogo sinteticheskogo beta-karotinai askorbinovoi kisloty na éndogennyi kantserogenez myshei.

Carcinogenesis in mice induced by the tryptophane derivative 3-hydroxyanthranilic acid was studied after administration of synthetic beta-carotene and ascorbic acid. The incidence of induced hemoblastoses and hepatomas was decreased 2-fold, while the latent period of their development was, increased in mice on a lifetime feed containing 15 mg/kg of beta-carotene. The anticarcinogenic effect of ascorbic acid added to drinking water was similar to that of beta-carotene. The additive inhibitory influence of beta-carotene and ascorbic acid on endogenous blastomogenesis was not found in mice.