Genetically modified animals as models of the pathological processes in psoriasis

Psoriasis is a chronic recurrent disorder that affects predominantly the skin and is autoimmune in nature. Experimental models help to study the development of psoriasis in controlled conditions and investigate particular aspects of the pathological process. Many mouse models were obtained to reproduce, to a certain extent, the psoriasis signs seen in humans. Genetically modified animals help to reveal the new genes whose mutations potentially underlie the disease and to search for new therapeutic targets. Moreover, the animal models are used to test new drugs and therapies. The review summarizes the published data on the laboratory animal models of the psoriatic process.     

Use of DNA in cytopenia induced by myelosan]

Wistar rats weighing 180-190 g received myleran per os in a single dose of 10 mg/kg, or fractionally (total dose of 25 mg/kg) for 18 days. After myleran administration the animals were injected 4-5 times (every other day) with a homologous DNA in a dose of 2 mg per rat or with a standard salt citrate. The DNA injection reduced the duration of leukopenia. With the least dose of myleran leukocyte count returned to the normal in 6 days in the treated animals and in 25 days in the untreated controls and with the highest dose -- in 15 and in 25 days, respectively, from the beginning of the treatment. The differences in the leukocyte count between the treated and control rats in both experiments were mainly due to the dynamics of neutrophils, the content of which in the treated animals exceeded that in the untreated animals by 54-110% in the course of 6-15 days in the first, and by 23-38% in the course of 10-23 days in the second experiment.     

Interaction of human thrombin I fragment, prethrombin I, and alpha-thrombin with tissue thromboplastin]

The binding of 125I-labeled prothrombin fragment I. prethrombin I and alpha-thrombin to native and papain-treated tissue thromboplastin in the presence of CaCl2 of EDTA was studied. The experimental curves plotted in the Scatchard coordinates testify to the presence in thromboplastin of two types of fragment I binding sites: those with a high (Kd = 7.6 x 10(-6) M) and moderate (Kd = 1.3 x 10(-8) M) binding affinity. The parameters of fragment I binding and their changes reproduced, for the most part, the mode of prothrombin binding observed in previous studies. The experimental results provide indirect evidence in favour of a hydrophobic role of Ca(2+)-dependent binding of prothrombin fragment I to thromboplastin. The binding of prethrombin I was nonspecific and Ca(2+)-independent, whereas alpha-thrombin showed a relatively high level of nonspecific electrostatic binding which was competitively inhibited by Ca2+. Thromboplastin proteins interacted (both directly and in a Ca(2+)-independent fashion) with all the prothrombin derivatives under study.     

Application of competitive immunoenzyme assay for analysis of group B fumonisins]

A varriant of competitive ELISA, making it possible to detect fumonisin B1 (up to 0.4 ng/well) was developed, based on the use of specific polyclonal antibodies obtained by immunization of rabbits with a horseradish peroxidase conjugate of fumonisin B1. The minimum concentration of fumonisin B in water-acetonitrile extracts of corn grain, dry corn products, and feeds, detected by the ELISA version developed is 0.2 mg/kg.     

Neuropharmacological profile of a high-affinity ligand of 5-HT1A receptors, 4-phenyl-1-[4-(2-naphtalimido)butyl]-piperazine

The neuropharmacological profile of 4-phenyl-1-[4-(2-naphtalimido)butyl]-piperazine (PNBP), a compound that possesses a high affinity for the serotonin receptors of 1A-type (5-HT_1A) and lacks an anxiolytic action, has been studied. Intracerebral administration of PNBP to rats through implanted cannulae into the hippocampal region resulted in no substantial behavioral changes during “open field” and “conflict situation” tests, as compared with those of control animals. At the same time, the behavioral effects of intraperitoneal administration of 10 mg/kg buspirone were completely abolished if buspirone had been jointly administered with 10 mg/kg PNBP. Moreover, combined application of 0.3 mg/kg PNBP and 0.3 mg/kg 8-OH-DPAT, an agonist of 5-HT_1A receptors, almost completely abolished the components of “serotonin syndrome” (prone position and stamping of the forepaws) in animals under study. These findings allowed us to conclude that PNBP has the properties of a competitive antagonist of buspirone and 8-OH-DPAT.     

Stepwise synthesis of oligonucleotides. XXXIV. Preparative synthesis of trinucleoside diphosphates and longer oligoribonucleotides using immobilized ribonucleases

Immobilized guanyl-specific ribonucleases from Aspergillus clavatus (C2), A. oryzae (T1), and Bacillus intermedius 7P (Bi) have been used for preparative synthesis of ten trinucleoside diphosphates, three tetra- and one pentanucleotide having the only guanylic acid residue at the 5'-end. The nucleotide sequence of the oligonucleotide synthesised determined the choice of the ribonuclease.     

Comparative study of the phospholipase activity of pathogenic and saprophytic Leptospira cultured on a serum-lecithin agar

The phospholipase activity of leptospires cultivated on serum-lecithin agar has been studied. Two zones of changes in the medium have been found to appear around the colonies of saprophytic Leptospira strains: transparent (5.25 +/- 2.09 mm wide) and turbid (6.90 +/- +/- 1.46 mm wide), which is linked with the production of phospholipases A and C. Only a single clear zone is formed around the colonies of pathogenic strains due to the production of phospholipase A. At the same time virulent Leptospira strains show greater phospholipase activity (the zones are 6.0 +/- 1.2 mm wide) than avirulent strains (the zones are 1.6 +/- +/- 0.04 mm wide).