[Dimephosphon restores functions of the injured spinal cord].

In clinical practice, dimephosphon is used as a vasoactive agent in cases of traumatic brain injury. We have studied the influence of dimephosphon on the functional recovery of dog spinal cord after lesion. The spinal cord trauma was modeled using the methods described by Allen. In a period of time from the 1st to 10th day after injury, experimental group of animals was treated intravenously with 2.5% dimephosphon solution (18.75 mg/kg).The recovery of conduction in descending spinal nerves was studied using the transcranial magnetic stimulation technique on the Neurotest complex comprising a transcranial magnetic stimulator and a computer analyzer. The state of sacrolumbar motoneurons was determined by the method of stimulation electromyography that allows both H-reflex and M-wave responses to be recorded. The status of experimental animals, their locomotor activity and pain sensation were evaluated using standard clinical assessment. Morphological analysis performed with paraffin sections (hematoxylin-eosin staining) demonstrated that dimephosphon decreased the initiation of apoptosis and necrosis and supported the recovery of injured parts of spinal cord. Thus, the results revealed a beneficial effect of dimephosphon administration on the functional recovery of injured spinal cord.

[Effect of xymedone on high-voltage-activated Ca2+ currents in pyramidal neurons of the entorhinal cortex].

The effect of xymedon on Ca2+ currents in entorhinal cortex LIII pyramidal neurons was studied using brain slices from 10-17-day old rats, which were analyzed by means of the infrared video assisted whole cell patch clamp recording. The sample slices were superfused with artificial cerebrospinal fluid containing tetrodotoxin, 4-aminopyridine, and tetraethylammonium for the blocking of Na+ and K+ channels, respectively. Xymedone was added to artificial cerebrospinal fluid and to all extracellular solutions. The slices were exposed to different concentrations of xymedone for 3 hours followed by patch-clamp recordings. Control recordings were run with the vehicle. Xymedone in a concentration of 0.01 mM decreased the maximum voltage-dependent Ca2+ current amplitude by 39.8 %, while 1 mM of xymedone inhibited the Ca2+ currents almost completely. The obtained data showed for the first time that xymedone exhibits a calcium channel blocker activity in neurons. Possible neuroprotective mechanisms of xymedone are discussed.

Mechanisms of the effect of 1,1-dimethyl-3-hydroxybutyl phosphonic acid derivatives on synaptic transmission in neuromuscular junction.

We studied the effect of homologues derivatives of 1,1-dimethyl-3-hydroxybutyl phosphonic acid on synaptic transmission in frog neuromuscular junction. Here we reviewed general mechanisms of inhibition of the postsynaptic current.

[Xymedon decreases phosphatidylserine membrane expression induced by proapoptogenic deficit of serum growth factors in Jurkat T-cells]. / Ksimedon snizhaet membrannuiu ékspressiiu fosfotidilserina, vyzvannuiu proapoptogennym defitsitom syvorotochnykh faktorov rosta v T-kletkakh Jurkat.

The effect of xymedone, a non-glucoside analog of pyridine nucleosides, on the apoptosis of human CD4+ T cells of the Jurkat line was studied by laser flow cytometry method. Xymedone decreased the membrane expression of phosphatidylserine and suppressed the increase in permeability of the cytoplasmic membrane, thus inhibiting the onset of a degradation stage of the apoptotic cascade. Possible mechanisms of the antiapoptogenic effect of xymedone within the framework of a (cytochrome C/caspase 3)-dependent signal pathway of the apoptosis are discussed.

[Experience with glyciphonic ointment therapy for primary multiple basal cell carcinoma of the skin]. / Opyt lecheniia pervichno-mnozhestvennogo bazal'nokletochnogo raka kozhi glitsifonovoi maz'iu.

The effectiveness of glycifone ointment treatment for primary multiple basal cell carcinoma of the skin was evaluated in 28 patients. 27 cases were cured following one or two courses the duration of which was determined by the number of foci, pattern of tumor and its total surface area.

Possible involvement of neurokinin receptors in CNS and neuromuscular synapse in the realization of the effects of CAPAH and substance P.

Nootropic non-anticholinesterase organophosphorus preparation CAPAH and substance P produced similar and dose-dependent effects on the amplitude and temporal parameters of miniature endplate potentials in mammalian neuromuscular synapse. Neurokinin receptor antagonist Win-51.708 abolished the effects of these agents. In behavioral experiments substance P moderated the mnemotropic and antidepressant effects of CAPAH. It was assumed that neurokinin receptors are the targets of CAPAH and substance P in CNS and neuromuscular synapse.

[Experience with glyciphonic ointment for malignant and precancerous lesions of the skin]. / Opyt primeneniia glitsifonovoi mazi pri rake i predrakovykh zabolevaniiakh kozhi.

Skin was smeared with glyciphonic ointment containing 30% of methylphosphonic diglycidyl ether (Tatkhimfarmpreparaty Company) in 495 patients with histologically confirmed basalioma and 36 patients with senile keratosis. During daily application necrotic tissue was removed. Considerable decomposition of tumor occurred on day 6 or later. It took the wound 9-12, seldom, 15 days to heal, with scars forming on days 15-20. Stable cure was registered (5-7 yrs) in 492 patients with skin basalioma and all cases of senile keratosis. No changes in peripheral blood count or any skin-resorption side-effects were recorded. Several patients suffered hyperemia, edema, itching or local pain.

[Glyciphonic ointment in the treatment of radiation-induced basal cell carcinoma of the skin]. / Lechenie glitsifonovoi maz'iu bazal'nokletochnogo raka kozhi, indutsirovannogo radiatsionnym izlucheniem.

Skin basalcell carcinoma of the head and neck occurring within 1.5-23 yrs on the site of radiation fibrosis were smeared daily with glyciphonic ointment without dressing the wound. Tumor disintegrated after 2-6 applications followed by edema tumor tissue development on days 22-24. After a 2-3 week interval, perifocal edema subsided, and tumor deed shrank leaving a small scab. Basalioma cells were detected underneath. Complete cure was recorded after another 2-3 week therapy in all cases. Only one patient relapsed three years later.

[The immunomodulator ximedon lowers the level of induced DNA damages in bone marrow and peripheral blood cells: the possibilities for immunogenetic correction]. / Immunomoduliator ksimedon snizhaet uroven' indutsirovannykh povrezhdenii DNK v kletkakh kostnogo mozga i perifericheskoi krovi: vozmozhnosti immunogeneticheskoi korrektsii.

It was established in experiments on albino unbred mice and during treatment of patients with osteomyelitis that 30 mg/kg of ximidon suppresses the formation of micronuclear polychromatophilic erythrocytes found in the bone marrow of mice and peripheral blood of patients with chronic osteomyelitis. The interrelationship of the results obtained with the modulating effect of ximidon on the mitochondrial, thiol, and adenylate cyclase-dependent mechanisms of cell regulation is discussed.

[Neuroprotective effect of kapakh, representative of new nootropic class non-anticholinesterase organophosphoric compounds]. / Neroprotektivnoe deistvie kapakh, predstavitelia novogo klassa nootropov-neantikholinésteraznykh fosforoorganicheskikh soedinenii.

In vivo and in vitro experiments revealed the neuroprotective activity of CAPAH, a representative of the new nootropic class phosphorylated carboxylic acid hydrazides. The mechanisms of this action, which were due to the membranous stabilizing activity of the drug and its affinity for glycine strychnine-sensitive sites of MMDA receptors (Ki = 8.8.10(-5) M). Six analogues of CAPAH have been also found to have affinity for these types of receptors; based on the examination of structure-affinity relationship, putative pharmacophores (only radicals of the benzene ring of a molecule in the para position exerted effects on affinity changes) were revealed. The findings give a deep insight into the mechanism of nootropic activity and open vistas for synthesizing phosphorylated carboxylic acid hydrazides as potential neuroprotective agents interacting with glycine strychnine-sensitive sites of MMDA receptor.

[The effect of pyrimidine derivatives on the sulfhydryl status of immunocompetent cells in vivo: the interrelationship with Ca2(+)-ATPase and antimutagenic activity]. / Vliianie pirimidinovykh proizvodnykh na sul'gidril'nyi status immunokompetentnykh kletok in vivo: vzaimosviaz' s Ca2(+)-ATFaznoi i antimutagennoi aktivnost'iu.

It was demonstrated in experiments on guinea pigs that a 30 mg/kg dose of ximedon changes the content of SH-groups in immunocompetent cells depending on the duration of drug administration and the organ to which the cells under test belong. Maximum increase of the SH-groups was recorded in the thymocytes. The dynamics of changes in Ca(2+)-ATPase activity repeated the fluctuations in the SH-group content in the splenic and bone marrow cells. In the bone marrow cells of CBA x C57B1 mice 3 mg/kg ximedon suppressed the induction of chromosome aberrations caused by cyclophosphane. The interrelationship of changes in the cell sulfhydryl status with Ca(2+)-ATPase activity and the antimutagenic effect of ximedon is discussed.

[Mechanisms of pyrimidine derivatives systemic immunomodulating effect]. / Mechanizmy sistemnogo immunomoduliruiushchego delstviia pirimidinovykh proizvodnykh.

Experiments on guinea pigs showed that xymedon in a dose of 30 mg/kg stimulates nucleic acid synthesis in thymocytes and increases the blood serum nucleic acid content. Xymedon increased secretion of endogenous DNA by human lymphocytes stimulated with PNA in vitro. The systemic immunotropic mechanisms of pyrimidine derivatives are discussed.

[The effect of ximedon on adaptation to prolonged immobilization stress]. / Vliianie ksimedona na adaptatsiiu k dlitel'nomu immobilizatsionnomu stressu.

It was shown in rabbit experiments that the use of ximedon in long-term immobilization stress limits activation of lipid peroxidation, stimulates the main enzymes of the antioxidant systems, causes of hypolipidemic, preventive endotheliotropic, and cardiotropic effect.

[Effect of pyrimidine derivatives on the regulation of active transport of calcium in the immunocompetent cells]. / Vliianie pirimidinovykh proizvodnykh na sistemu reguliatsii aktivnogo transporta kal'tsiia v immunokompetentnykh kletkakh.

Experiments with guinea pig immunocompetent cells and nonadherent and adherent mononuclear fractions of the peripheral blood of healthy donors, and patients with rheumatoid arthritis and purulent surgical infection disclosed different levels of Ca(2+)-ATPase activity. Thymectomy in adult guinea pigs led to diminution of activity of the enzyme in all lymphoid organs. The effect of ximedon (30 mg/kg) on Ca(2+)-ATPase activity depended on the thymus and duration of treatment with the drug, and was of a two-phase character.

[The toxicity and biological effects of organophosphorus epoxides]. / Toksichnost' i nekotorye biologicheskie éffekty fosfororganicheskikh époksidov.

In the series of glycidylic ethers of alkylophosphoric and methylphosphoric acids three types of compounds have been identified: those possessing anticholinesterase, narcotic, and antineoplastic activity. Monoglycidylic ethers of diethyl- and diisopropylphosphoric acids and diglycidylic ether of ethylphosphoric acid caused intoxication of animals with the cholinergic excitation syndrome, and in vitro in a concentration of 1 mmol/liter strongly inhibited cholinesterase, stimulated the motor activity of an intestinal segment, but did not demonstrate cytotoxic activity in relation to NK/Ly strain tumor cells. Monoglycidylic ethers of di-n-propyl-, di-iso-butyl, and di-n-butyl-phosphoric acids as well as diglycidylic ethers of n-butyl- and iso-amylphosphoric acids caused a "hypnotic state" in the animals, suppressed the motor activity of an isolated intestinal segment, considerably increased the number of diffusely stained by Aizenman's [correction of Aisenmanns'] method cells of ascitic NK/Ly tumor in vitro, but poorly inhibited the growth of this tumor in chemotherapeutic experiments. Diglycidylic ethers of methyl-, n-propyl-, iso-butylphosphoric, and methylphosphonic acids caused poisoning of the type of intoxication by alkylating agents, weakly influenced cholinesterase activity, did not change the character of contractions of the intestinal segment. In vitro they caused a strong cytotoxic effect, but delayed the growth of the NK/Ly tumor treated animals by 84-100%. The possibility of the phosphororganic epoxides under study taking part in the reactions of alkylation and phosphorylation is suggested.