The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
Within the framework of the international project Kolarctic «Food safety and health in the border areas of Russia, Finland and Norway» in the Pechenga district of the Murmansk Region, 100 blood samples were selected from men, women and gravidae in autumn 2013. In blood plasma of 40 persons analyzed in the laboratory of the Northwest branch of the Research and Production Enterprise «Typhoon”the following POPs were detectable: HCB, HCH Group, DDT and PCBs groups. In the HCH group, beta-isomer prevailed; alpha-HCH was detected in 28% of female blood samples; gamma-HCH –in 50% of women and in 22% of pregnant women. The presence of HCH isomers in the blood of examined individuals was uniquely associated with other nutrition sources (unlike local food) as HCH is not present in the local food. In DDT group, 4-4’-DDE and 4,4’-DDT dominated; other metabolites are rarely encountered. At the same time, 4’-4DDE was detected in 22% of pregnant women which gives evidence of a DDT probable domestic «fresh» source at the maternity ward in Nickel settlement. Mean levels of HCB, beta-HCH, 4,4’-DDE, 4,4’-DDT among examined individuals are ranged between 0.13 and 1.4mg /l in blood plasma. Of fifteen PCB congeners analyzed in the blood of examined persons from three population groups, the highest «contribution» to the total PCB is made by the following congeners:: # 118 (17-25%), # 138 and # 153 ( 11-17% each), # 52 (10-14%) and # 101 (8-9% ). In whole, share parts of PCB congeners in blood of the population examined correspond to those in local foodstuff. Average levels of total PCB in the population groups examined are not high – about 1mg /l in plasma of pregnant women and 1.5 mg /l in male and female plasma . None of individuals examined (including gravidae) showed an excess over international recommended levels of total PCB in blood. The content of HCB, PCBs 4,4’-DDE and PCB # 153 in the population blood in the Pechenga district is the lowest in comparison with other regions of the Russian Arctic areas (from the Murmansk region to Chukotka), and among the gravidae it is similar to that in neighboring northern Norway.
Keywords: persistent organic pollutants (POPs), HCB, HCH, DDT, PCB congeners, exposure, blood plasma, pregnant women, recommended levels, level of concern, exposure level, Murmansk Region, Russian Arctic
Carbon oxide poisoning leads to the development of delayed CNS functions disturbances. These disturbances may be not only linked to the development of hemic hypoxia. In a number of research works, nonspecific neurotoxic carbon oxide mechanisms of action were described, one of which is activation of programmed cell death developing as apoptosis. One of the preparations having neuroprotective action mode is a synthetic analog sequence of adrenokortikotropic hormone – KK1 peptide. In this research, laboratory animals were exposed to acute heavy carbon oxide poisoning in a dose of 0.8 LC50 within 30 min. KK1 peptide was administrated intranasally in a dose of 40 mkg/kg/day within 5 days. In rats brain gomogenates, the maintenance of active forms of marker proteins associated with apoptosis early stages was investigated at different time after intoxication with carbon oxide. As a result of the conducted research, it was established that the use of KK1 peptide leads to the decrease of the maintenance of r53 protein active forms and Akt1 protein kinase on 7th and 14th days after a heavy poisoning with carbon oxide. Results of the experiment performed allow to suggest that at that type of pathology the potential mechanism of neuroprotective effect of synthetic KK1 tetrapeptide is connected with restricted development of apoptosis in brain.
Keywords: carbon oxide, neurotoxicity, apoptosis, Akt1 protein kinase, r53protein, KK1 peptide
Results of morphological studies of brain after acute poisoning with ethanol and its correction with combination of molixan and semax are reported. 40% ethanol solution was intragastrically administered at a dose of 12 g / kg, which corresponded to 1.5 LD50. Semax was intranasally administered in a dose of 3 mg / kg. Molixan was administrated intraperitoneally in a dose of 30 mg / kg. The efficacy of peptide drugs was evaluated according to four application schemes: prophylactic (once 1 hour before ethanol), prophylactic and treatment (1 h prior to and immediately after administration of ethanol), early treatment (immediately after administration of ethanol and then once daily for 2 consecutive days), and delayed treatment (30 min after administration of ethanol and then once daily for 2 consecutive days). The preparation of material for the morphological study was performed 1 hour, 3 hours, 1 day and 3 days after modeling of alcohol intoxication. It was found out that ethanol at a dose of 1.5 LD50 causes congestion and stasis in the blood vessels of the pia mater, plasma-mpregnation of endothelium, microvascular damage to the blood-brain barrier that is followed by increase in their permeability, penetration of erythrocytes outside blood vessel walls, perivascular edema in brain tissue, change in shape and size of neurons (wrinkling of neurons). It was shown that the prophylactic and treatment application of the molixan and semax combination causes a reduction of ethanol toxic effects, which is manifested in significantly decreased plasmorrhagia severity and in the absence of wrinkled neurons.
Keywords: poisoning, ethanol, molixan, semax, brain, morphological structure
Individual and combined effects of sodium nitrite and amine (p-toluidine) including additional light stress conditions on laboratory mice were investigated. It has been established that the physical impact (light stress) for 107 days causes a significant increase in serum alanine aminotransferase activity and decrease of gammaglutamyltransferase activity in laboratory mice. A slight increase in the studied parameters of protein metabolism (urea and creatinine) in mice exposed to light stress was observed. Under exposure additional to chemical stress (enteral injection of a combination of sodium nitrite and p-toluidine), the activity of the enzymes indicator in serum increases: alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. A decrease in the activity of gamma-glutamyl transferase under combined action of stress conditions of various nature compared to the control was found. The observed effects of stress factors on the enzyme activity of blood serum correlate with pathomorphological changes in the esophagus and stomach.
Search for effective treatment methods for patients with acute poisoning caused by neuroleptics was motivated by frequent complications and lethality induced by that type of pathology. The object of the present study was a comparative evaluation of application effectiveness of plasma ferase and plasma ferase in combination with antihypoxic cytiflavin as therapy methods to cure acute severe poisonings with azaleptini. The inclusion of substrate anti hypoxic cytoflavin in intensive therapy on the background of extra corporal detoxification methods ( plasma ferase) has a positive effect on the course of acute severe poisonings by azaleptini and manifests in a shorter duration of comatose state, lesser development of pulmonary complications, shorter terms of inpatient hospital treatment and decreased lethality as well. The combined use of plasma ferase and cytoflavin significantly reduces hypoxia and endogenous intoxication.
Keywords: azaleptini, acute poisonings, cytoflavin, plasma ferase
The application effectiveness of hyperbaric oxygenation in complex therapy of acute intoxication by carbon oxide gas was carried out depending on inhalation injury. It was shown that in the presence of airways thermo-chemical lesions , hyperbaric oxyenation sessions mainly began in the somatogenic phase. The presence of the third-degree injury of airways posed a contraindication for hyperbaric oxygenation sessions, especially in older persons.
Keywords: poisonings, carbon oxide gas, thermo-chemical injury of airways, hyperbaric oxygenation
Genotoxic effect of ultra-low doses of toxic chemicals may cause delayed health effects. For their assessment, chromosomal aberrations (CA) in 138 persons from among the staff of chemical weapons storage and destruction facilities( objects) were analyzed. The control group consisted of 55 people. A statistically significant increase in levels of CA ( 5.10 ± 0.29 vs. 1.67 ± 0.21; U = 1471; p = 0.0001) was shown, mainly due to chromatid -type CA -single pieces (3.98 ± 0.25 versus 1.20 ± 0.16, U = 1503; p = 0.0001) and chromatid exchanges, (0.12 ± 0.03 vs. 0,00 + 0.03, U = 3248; p = 0,002 ), which is typical to chemical mutagenesis. A statistically significant increase in the level of unstable exchanges of chromosomal-type aberrations (0.17 ± 0.03 vs. 0.03 ± 0.02; U = 3190 p = 0.003) was also observed, possibly due to the synergistic action of toxicants and physical factors. An average number of CA per cell was significantly higher than the control values (1.09 ± 0.02 vs. 1.00 ± 0.00; U = 2733; p = 0.0001). Statistically significant differences in the distribution of individuals with different levels of CA among employees of the objects and in the control group were shown. Data obtained suggest a pronounced genotoxic effect and the possibility of using CA analysis to assess individual professional risk to the staff of the objects.
Keywords: genotoxicity, chemical weapon, chromosomal aberrations, genetic risk, delayed health effects
SPECIFICITIES OF DETECTION OF FENTANYL DERIVATES IN URINE USING METHODS OF LIQUID AND GAS CHROMATOGRAPHY-MASS SPECTROMETRY Recently in the Leningrad region, cases of poisoning associated with taking fentanyl derivatives (Carfentanyl, 3-Methylfentanyl) became more frequent. Analytical information about taking those compounds by persons brought to central district hospitals with symptoms of drug intoxication gives rise to certain methodological difficulties that are caused by low concentrations of toxic substances in blood and urine and limited metabolism data. Using methods of liquid and gas chromatography-mass spectrometry (GC-MS and LC-MS / MS), urinary metabolites of fentanyl derivatives were identified. Methods for samples preparation based on liquid-liquid or solid-phase extraction are suggested. It is recommended to use LC-MS/MS methods to detect metabolites and unmodified forms of fentanyl derivatives in blood and urine of patients under examination. Results of the practical application of developed methods are reported.
Keywords: poisoning, derivatives of fentanyl, 3-Methylfentanyl, Carfentanyl, «designer drugs»
The article describes a clinical observation of a patient brought to the Center for treatment of acute poisonings at I.I. Dzhanelidze Research Institute of Emergency Care with severe acute oral poisoning by sodium chloride The results of clinical, laboratory, instrumental and postmortem studies are reported.
Keywords: sodium chloride, acute poisoning, peroral uptake