[Personalized character of toxic effects through mass nonlethal poisoning by phenazepam and other psychoactive substances]. / Personifitsirovannyi kharakter toksicheskikh effektov na primere massovykh nesmertel'nykh otravlenii fenazepamom i drugimi psikhoaktivnymi veshchestvami.

Over several months, 14 people were admitted in 6 hospitals with severe symptoms of intoxication with psychoactive substances as a result of mass poisoning. All symptoms occurred after taking a drink that contained crushed phenazepam tablets. Samples of blood (n=10) and urine (n=6) taken from 14 sufferers for forensic, chemical and toxicological examination were analyzed using the HPLC-MS/MS method. Phenazepam was detected in the biomaterial of all 14 patients. Other psychoactive substances (baclofen, pregabalin, chlorprothixene, chlorpromazine, phenibut, tramadol, diazepam), narcotic substances and ethanol were also found in the sufferers. The phenazepam concentration in the blood was in the range of 109.75-786.50 ng/ml, in the urine - 8.97-101.28 ng/ml. The pharmacokinetic and toxicokinetic characteristics of toxicants as well as additional factors characterizing the phenotype of the sufferer in addition to drug's content in the biological material must be taken into account to determine the toxicity level of phenazepam against the background of combined action with other psychoactive substances.

Mechanical Transformation of Compounds Leading to Physical, Chemical, and Biological Changes in Pharmaceutical Substances.

This study demonstrates the link between the modification of the solid-phase pharmaceutical substances mechanical structure and their activity in waters with different molar ratio «deuterium-protium¼. Mechanochemical transformation of the powders of lactose monohydrate and sodium chloride as models of nutrients and components of dosage forms was investigated by the complex of physicochemical and biological methods. The solubility and kinetic activity of substances dispersed in various ways showed a positive correlation with the solvent isotope profile. Substances dissolved in heavy water were more active than solutes in natural water. Differential IR spectroscopy confirmed the modification of substituents in the sample of lactose monohydrate, demonstrating physicochemical changes during mechanical intervention. The biological activity of the compounds was determined by the method of Spirotox. The activation energy was determined by Arrhenius. Compared with the native compound, dispersed lactose monohydrate showed lower activation energy and, therefore, greater efficiency. In conclusion, proposed data confirm the statement that mechanical changes in compounds can lead to physicochemical changes that affect chemical and biological profiles.

[The determination of amitriptyline and its metabolite, nortriptyline, in the biological objects of the corpse by the high-performance liquid chromatography technique].

Tricyclic antidepressants are among the preparations that most frequently cause intoxication in adults and children; moreover, poisoning with these substances not infrequently has a fatal outcome. Medications belonging to this group, such as amitriptyline, are extensively used to manage manifestations of depression, anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline overdosage causes non-specific symptoms of intoxication, and its clinical picture does not allow to identify the nature of a psychotropic xenobiotic. Of primary importance in connection with this is to establish the cause of intoxication or death by the clinical toxicological and forensic medical methods based on the results of the fast identification and quantitation of amitriptyline in biological materials including blood, urine, hepatic tissues, etc. The authors describe the method for the determination of amitriptyline and its principal physiological metabolite nortriptyline in biological objects with the help of high performance liquid chromatography (HPLC).

[The problems of expert evaluation of the results of forensic chemical investigations of clozapine in the biological material].

The objective of the present review was to analyse the problems of expert evaluation of the results of forensic chemical investigations of clozapine in the biological material. Such an analysis is needed because many topical aspects of the quantitative evaluation of toxic clozapine concentrations remain unclear. The treatment with clozapine is associated with its accumulation in blood in concentrations up to 2 mg/l in the absence of any toxic effect allegedly due to the development of tolerability of this agent. In the tolerant patients the ratio of the main clozapine metabolite, norclozapine, to clozapine itself in the serum amounts to 0.6-0.9. This value falls down to 0.3-0.4 in case of acute intoxication. In the case of identification of other pharmaceutical products narcotic drugs together with clozapine their influence on the activity of enzymes responsible for clozapine biotransformation should be taken into consideration. The concomitant intake of clozapine and alcohol may be dangerous for the clozapine-intolerant subjects. It is concluded that the above observations must be borne in mind in the assessment of the results of forensic chemical analysis.

[The influence of an air ionizer on the air ionic composition].

The air ionic composition in a classroom was determined during the operation of a Neo Tec XJ-2100 ionizer (Germany). The amount of ions in the air was measured before and after the switch-on of the ionizer. It was shown to vary depending on the mode of operation of the device and differ from the recommended normal values. The necessity of checking up the work of air ionizers both in living quarters and at workplaces is discussed with the application of air ion counters making it possible to carry out monitoring of the air ionic composition and estimate its compliance with the sanitary and hygienic norms.

[Specific features of toxicological profile of gemcitabine, an antitumour agent from the group of anti-metabolites].

Gemicitabine (2',2'-difluorodesoxycitidine) is a relatively new medicinal product from the group of anti-metabolites used as the first line therapy of pancreatic cancer, non-pulmonary cancer, and breast cancer. However, analysis of its toxicity spectrum revealed a large number of adverse events associated with the clinical application of this product. This fact is ascribed to the narrow range of therapeutic usages of this cytostatic preparation (from 25 mg/kg to 27 mg/kg). This paper is designed to summarize the available data on hematological, gastrointestinal, pulmonary, and cardiotoxicity of gemcitabine. They may be useful for the improvement of control over gemcitabine toxicity, correction of its dosage regime, and efficacious prevention of the most serious side effects.

[Prognostication of toxicity of a group of chemical compounds comprising anti-tuberculosis medicines by the quantitative structure-activity correlation method].

Balaban (J), Wiener (W), and Rouvray (R) topological indices as well as detour (Ip) and electropy (Ie) indices reflecting the structure of chemical substances were used to establish correlation between median lethal dose (LD50) of an anti-tuberculosis medicine and its molecular structure. Monocyclic compounds showed linear correlation between LD50 values and Balaban index (R = 0.93). Correlation between a maximum daily dose and electropy index was typical of the products having a more complicated structure. Results of this study open up prospects for the development of new anti-tuberculosis medicinal preparations characterized by reduced toxicity.

Laser diffraction for standardization of heterogeneous pharmaceutical preparations.

A new quantitative method for standardization of heterogeneous pharmaceutical preparations and their quality control during storage based on laser diffraction is proposed. A series of pharmaceutical dosage forms--suspensions, emulsions, tinctures, decoctions, cell preparations and others, are heterogeneous medicines. In some cases disperse phase can be formed during storage as a result of layering (L1/L2) or precipitation (S/L). Laser diffraction method proposed in this study can be used for standardization and quality control of medicines.

[Toxicity of non-steroid anti-inflammatory drugs]. / Nesteroidnye protivovospalitel'nye sredstva: k voprosu o toksichnosti.

Data are reported on toxicity of a majority of non-steroid anti-inflammatory drugs (NSAD), which are the most frequently used in clinical practice and whose chemical structures are different. The action mechanism and side effects of some NSAD, in particular, of diclofenac, ibuprofen and indometacin, are also in the focus of attention.

[Toxic effects of heavy metal salts on intact and irradiated cultured mammalian cells]. / Toksicheskoe deistvie solei tiazhelykh metallov na intaktnye i obluchennye kul'tiviruemye kletki mlekopitaiushchikh.

The toxicity of solutions of K2Cr2O7 and NiSO4.8H2O for cultivated Chinese hamster fibroblasts and murine lymphoma Sp-2 cells was determined using three criteria of damage: cell death (dyeing with trypan blue), inhibition of cell proliferation and their colony-forming activity. It was shown that both salts have equal toxicity in (10(-3)-10(-2)) M interval for both culture investigated relative to inhibition of cell proliferation. The threshold of toxicity of K2Cr2O7 relative to reproductive cell death (10(-4) M is smaller than to the inhibition of cell proliferation. The nontoxic concentration of K2Cr2O7 enhanced the radiation-induced reproductive death of fibroblast culture at doses 2 and 4 Gy.