[QSAR investigation of acute toxicity of organic compounds during oral administration to mice]. / QSAR-analiz ostroi toksichnosti organicheskikh soedinenii pri peroral'nom vvedenii mysham.

The effect of the structure of organic compounds on the acute toxicity upon oral injection in mice was studied using 2D simplex representation of the molecular structure and Random forest (RF) methods. Satisfactory quantitative structure-activity relationship (QSAR) models were constructed (R2 test = 0,61-0,62). The interpretation of the obtained QSAR models was carried out. The contributions of known toxicophores with established mechanisms of action were calculated in order to confirm the ability of the interpretation approach to correctly rank them relative to other structural fragments. The influence of the molecular surroundings of some toxicophores was analyzed. We analyzed the contributions of other highly ranked fragments from the list of common functional groups and ring systems in order to find new potential toxicophores. The on-line version of the expert system "OCHEM" (https://ochem.eu) and Arithmetic Mean Toxicity (AMT) approach were used for a comparative QSAR study.

Arginine-vasopressin in nucleus of the tractus solitarius induces hyperglycemia and brain glucose retention.

Hypothalamic arginine-vasopressin (AVP) plays an important role both as a neurotransmitter and hormone in the regulation of blood glucose and feeding behavior. AVP-containing axons from the parvocellular subdivision of paraventricular nucleus of the hypothalamus terminate in the nucleus of the tractus solitarius (NTS), but the function of this projection is not known. Interestingly, the NTS also receives afferent information from the carotid body and other peripheral receptors involved in glucose homeostasis. We have previously reported that stimulation of the carotid body receptors initiates a hyperglycemic reflex and increases brain glucose retention. Here we show that direct administration of micro-doses of AVP into the NTS of anesthetized or awake rats rapidly increased the levels of blood glucose concentration and brain arterio-venous (A-V) glucose difference. This effect was not observed when the same doses of AVP were injected in the brainstem outside NTS. Arginine-vasopressin antagonist microinjections alone produced a small but significant reduction in brain A-V glucose. Pre-administered VP1-receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1),O-Me-Tyr(2),Arg(8)]vasopressin blocked the effects of AVP. These results indicate that AVP acting on its receptors locally within the NTS participates in glucose homeostasis, increasing both blood glucose concentration and brain A-V glucose differences. Hypothalamic AVP may facilitate hyperglycemic responses initiated by peripheral signals processed at the level of the NTS.

CheD: chemical database compilation tool, Internet server, and client for SQL servers.

An efficient program, which runs on a personal computer, for the storage, retrieval, and processing of chemical information, is presented, The program can work both as a stand-alone application or in conjunction with a specifically written Web server application or with some standard SQL servers, e.g., Oracle, Interbase, and MS SQL. New types of data fields are introduced, e.g., arrays for spectral information storage, HTML and database links, and user-defined functions. CheD has an open architecture; thus, custom data types, controls, and services may be added. A WWW server application for chemical data retrieval features an easy and user-friendly installation on Windows NT or 95 platforms.

The action of agonists and an antagonist of GABA on the frequency composition of the electrical activity of various brain structures of rats.

The frequency composition of the electrograms (EG) of the visual area of the cortex and deep brain structures (putamen, dorsal hippocampus, medial portion of the mid-hypothalamus) were investigated in chronic experiments in 36 awake rats under the conditions of the separate and combined introduction of GABA, its agonists (muscimol, baclofen), and an antagonist (bicuculline) into the lateral ventricle of the brain. The principal effects were manifested primarily in the form of a decrease in the power of the oscillations in the 7-16 Hz region of the range (1-25 Hz) of EG frequencies analyzed. Even though these changes were unidirectional following the administration of the agonists, they nevertheless differed with respect to the degree of expressivity in the different structures. Bicuculline, injected against the background of the action of muscimol and baclofen, attenuated the effects induced by them. The possible mechanisms of the phenomena discovered are discussed.

Electrical activity of the hippocampus of rats with the central administration of GABA agonists and antagonists.

The frequency spectra of the electrograms of the dorsal hippocampus with intraventricular administration of GABA, muscimol, baclofen, bicuculline, and picrotoxin, were studied in chronic experiments on 24 awake freely-moving rats. The data obtained are in accord with the existing notion regarding the interactions of agonists and antagonists with GABA receptors. The possibility of their participation in the formation and/or modulation of the total electrical activity of the hippocampus is discussed.