Acute hemolysis caused by incidental trichlorfon exposure.

Trichlorfon (o-o-dimethyl-2,2,2-trichloro-hydroxyethylphosphate), an organophosphate, has a moderately potent anticholinesterase activity. Organophosphate poisoning is well known for its characteristic symptoms and signs, but acute hemolysis caused by trichlorfon is rarely reported. We present a patient who developed acute hemolysis and renal function impairment after percutaneous trichlorfon exposure. A 54-year-old man applied trichlorfon powder to his dog to kill its parasites. Half an hour later, the dog was suspected to die of cholinergic crisis and the patient felt abdominal cramping pain. Later, he developed severe nausea, vomiting, chills, high fever, and cold sweat. Laboratory work-up disclosed a picture of acute hemolysis, jaundice, renal function impairment and leukocytosis. However, there were no clinical features of acute cholinergic syndrome except gastrointestinal symptoms, and blood cholinesterase activities were also normal. He eventually had a full recovery. Trichlorfon should be added to the toxins known to cause acute hemolysis.

[Relationship between acute dipterex poisoning and oxidative stress and free radical damage].

OBJECTIVE: To study relationship between acute dipterex poisoning and oxidative stress and free radical damage. METHODS: Eighty-two patients with acute dipterex poisoning (ADPP) and ninety-two healthy adult volunteers (HAV) were enrolled in the study with randomized controlled trial design. Plasma levels of vitamin C (VC) and vitamin E (VE), as well as level of lipoperoxide (LPO) and activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in the red blood cells (RBC), were determined by spectrophotometry. RESULTS: Levels of VC and VE, and activities of SOD and AChE were (37.35 +/- 9.98) micromol/L, (16.57 +/- 4.54) micromol/L, (1 785 +/- 154) U/g Hb and (213.1 +/- 57.6) U/g Hb, respectively, in the ADPP group, significantly lower than those in the HAV group, (55.34 +/- 15.98) micromol/L, (25.66 +/- 7.24) micromol/L, (2 124 +/- 185) U/g Hb and (305.3 +/- 83.6) U/g Hb, respectively. Plasma level of LPO was (35.20 +/- 5.29) nmol/g Hb in the ADPP group, significantly higher than that in the HAV group, (27.87 +/- 4.66) nmol/g Hb. Partial correlation analysis suggested that there existed negative correlation between activity of AChE in the RBC and plasma level of LPO (r = -0.274, P = 0.013) and positive correlation between activity of AChE in the RBC and plasma levels of VC and VE, and activity of SOD in the RBC (r = 0.333, P = 0.002, r = 0.269, P = 0.015 and r = 0.248, P = 0.026, respectively) in the ADPP, adjusted for age. Coefficient of reliability alpha was 0.682 (P < 0.001), with a standardized alpha of 0.868 (P < 0.001). CONCLUSION: There exist severe oxidative stress and free radical damage in patients with acute dipterex poisoning.

Oxidative stress and free radical damage in patients with acute dipterex poisoning.

OBJECTIVE: To investigate whether acute dipterex poisoning (ADP) may cause oxidative stress and free radical damage in the bodies of acute dipterex poisoning patients (ADPPs), and to explore the mechanisms by which ADP may cause oxidative stress and free radical damage. METHODS: Fifty ADPPs and fifty healthy adult volunteers (HAVs) whose ages, gender and others were matched with the ADPPs were enrolled in a randomized controlled study, in which concentrations of nitric oxide (NO), vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as concentration of lipoperoxide (LPO), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric analytical methods. RESULTS: Compared with the average values of experimental parameters in the HAVs group, the average values of plasma NO and erythrocyte LPO in the ADPPs group were significantly increased (P<0.0001), while those of plasma VC, VE and beta-CAR as well as erythrocyte SOD, CAT, GPX and AChE in the ADPPs group were significantly decreased (P<0.0001). Bivariate correlation analysis and partial correlation analysis suggested that when NO and LPO values were increased, and VC, VE, beta-CAR, SOD, CAT and GPX values were decreased in the ADPPs, AChE value was decreased gradually in the ADPPs (P<0.001-0.0001). Reliability analysis of experimental parameters reflecting oxidative stress and free radical damage in the ADPPs showed that the reliability coefficient (8 items) alpha=0.6909, and the standardized item alpha=0.8574. CONCLUSION: The findings in the present study suggest that ADP can cause oxidative stress and free radical damage, and inhibit markedly erythrocyte acetylcholinesterase activity in ADPPs.

[The pharmacokinetic interaction of cholinolytics and cholinesterase reactivators as a reflection of the modulation of their binding in blood plasma and in brain tissue]. / Farmakokineticheskoe vzaimodeistvie kholinolitikov i reaktivatorov kholinésterazy kak otrazhenie moduliatsii ikh sviazyvaniia v plazme krovi i v tkani mozga.

Radioligand assay showed that the cholinesterase (ChE) reactivators dipiroxime and benzyxime, but not carboxime, modulate selective absorption of some cholinolytics (tributam, pediphen, aprophen) in rat brain. Significant suppression of the specific binding of muscarine antagonists was recorded after chlorophos (2.LD50) intoxication. Under such conditions, the ChE reactivators induce increase in the number of binding sites and in the parameters of the constant of cholinolytic absorption on the brain membranes. It was also established by equilibrium dialysis that the binding of cholinolytics in blood plasma under the effect of ChE reactivators is reduced, leading to redistribution of their free and bound fractures, which is most favorable for tissue sorption.

Human mortality in organophosphate poisonings.

We reviewed 130 admissions of organophosphate poisoning and analyzed the causes of death. Fenitrothion, malathion, dichlorvos, trichlorfon and fenitrothion/malathion were the most frequent chemicals involved. Mortality was 25% (32/130); delay in discovery and transport (18 cases), insufficient respiratory management (8 cases), and severe underlying or co-existing diseases (6 cases) were noted in the lethalities. Insufficient respiratory management consisted of delay in endotracheal intubation (5 cases) and failure in weaning (3 cases). About 3/4 of the severely serum cholinesterase-depressed cases needed ventilators. This suggests that better respiratory management would improve the outcome of organophosphate poisonings. Close observation of the clinical symptoms is essential, and detection of changes in serum cholinesterase may be helpful.

[Chromatin-protective action of the biologically active preparation BTK-8L in tetrachloromethane and chlorophos poisoning]. / Zashchitnoe po otnosheniiu k khromatinu deistvie biologicheski aktivnogo kompleksa BTK-8L v usloviiakh intoksikatsii tetrakhlormetanom i khlorofosom.

Results obtained from the study of the interaction between the phytosteroid preparation (BTK-8L) and fractionated rat liver nuclear chromatin under conditions of the tetrachloromethane and chlorophos intoxications are described. It is shown that preventive injection of BTK-8L to the animals has a partial protective effect on transcriptionally active and repressed liver chromatin. This preparation interacts with chromatin histone proteins binding with them and changes the nucleoprotein complex structure as a results of which the chromatin fraction components become less accessible to the damaging action of tetrachloromethane and chlorophos. The BTK-8L protective effect is exhibited on the DNA replication and transcriptional levels under conditions of tetrachloromethane and chlorophos intoxications.

Human germinal mutagenic effects in relation to intentional and accidental exposure to toxic agents.

This paper presents examples of epidemiological evaluation of exposure- and cluster-type mutations in human populations. The self-poisoning model did not show that offspring born from mothers after a semi-lethal self-poisoning had higher rates of prenatal selection (fetal death) or abnormalities due to germinal mutations; however, an intrauterine growth retardation was found. The surveillance function of the Hungarian Congenital Abnormality Registry has detected many cluster-type situations, one example of which is an extreme increase of Down's syndrome in a small Hungarian village in 1989 to 1990. Environmental investigations have pointed to the excessive use of trichlorfon at local fish farms as the cause.

[Prognostication in chronic pesticide poisoning in agricultural workers: state of lipid metabolism]. / Prognozirovanie khronicheskoi intoksikatsii pestitsidami u sel'skokhoziaistvennykh rabochikh po sostoianiiu lipidnogo obmena.

The authors discuss a possibility to estimate risk of chronic intoxication by 2,4-D agricultural preparations and phosphorus organic pesticides among rural inhabitants having occupational contact with the chemicals. The estimation could be based on lipid metabolism parameters.

[Optimization of artificial pulmonary ventilation in patients with organophosphorus compound poisoning complicated by development of exotoxic shock]. / Optimizatsiia provedeniia IVL u bol'nykh s otravleniiami fosfororganicheskimi soedineniiami, oslozhnennymi razvitiem ékzotoksicheskogo shoka.

Central hemodynamics, phase structure of left-ventricular systole, and paO2 were studied in 104 patients with organophosphorus poisoning complicated by exotoxic shock during forced ventilation of the lungs (FVL) with positive zero expiration pressure, positive end expiration pressure +5, +7, +10 cm H2O, and high-frequency FVL. FVL with positive end expiration pressure +5 or +10 cm H2O was found to be the optimal for patients with compensated shock. In patients with decompensated phase of exotoxic shock FVL with positive zero expiration pressure and FVL with positive end expiration pressure +5 cm H2O, although having no negative impact on the hemo- and cardiodynamics, did not provide sufficient oxygenation of the blood. Higher values of positive end expiration pressure (+7, +10 cm H2O) brought about disorders of heart work. High-frequency FVL appears to be the most rational in patients with decompensated phase of shock.

[Genoprotective effect of drugs based on ecdysteroids in poisoning of rats with tetrachloromethane and chlorophos]. / Genoprotektornyi éffekt preparatov na osnove ékdisteroidov pri otravlenii krys tetrakhlormetanom i khlorofosom.

Molecular mechanisms of chromatin damage have been investigated during tetrachloromethane and chlorophos intoxication of experimental animals. Introduction of tetrachloromethane to experimental animals induced chromatin degradation causing a partial loss of histone H1-DNA fragmentation and formation of intermolecular bonds: DNA-protein. Intoxication with chlorophos results in repression of a part of genes due to augmented chromatin compactness. Preventive introduction of the steroid preparation from Serratula coronata L. to experimental animals exerts a genoprotective effect, probably, as a result of derepression of genes responsible for reparation of chromatin structure.

[Lipid peroxidation and calcium transport in rat liver microsomes after chlorofos poisoning and the effect of atropine and verapamil]. / Perekisnoe okislenie lipidov i transport Ca2+ v mikrosomakh pecheni krys pri intoksikatsii khlorofosom i deistvii atropina i verapamila.

Structural and functional state of rat hepatocytes endoplasmic reticulum membranes intoxicated with chlorofos (0,0-dimethyl-(1-oxy-2,2,21-trichloroethylphosphonate) was studied. It was shown that in case of intoxication a breakage of the membrane Ca(2+)-transport function was accompanied by modification of the membrane phospholipid lipoperoxidation processes and by conformational change of proteins. It is established that prophylactic injection of m-cholinolytic atropine and Ca(2+)-channel antagonist verapamil lead to normalization of processes of ATP-dependent potassium ion transport and lipid peroxidation processes (LPO) in the liver microsomal membranes of intoxicated animals.

[Mechanisms of the genoprotective action of a phytoecdysteroid drug (BTK-8L) in chromatin damage by chlorofos]. / Mekhanizmy genoprotektornogo deistviia preparata na osnove fitoékdisteroidov (BTK-8L) v usloviiakh povrezhdeniia khromatina khlorofosom.

Genoprotective effect of preparation BTK-8L from plant steroids at prophylactic injection to experimental animals at chromatin damage by chlorofos was revealed. Antioxidant action of the preparation, being most highly expressed in the transcriptionally active chromatin fraction, is, probably, the most likely mechanism of the action. The realization of this action might be carried out as a result of the direct binding of BTK-8L with the chromatin protein-lipid complex, which was revealed during the analysis of the model systems showing binding of the preparation with chromatin fractions in vitro. Correction of structural chromatin organization and its transcriptional activity modified with intoxication of animals by chlorofos may occur as a result of such binding. Genoprotective properties in BTK-8L correlate to some extent with the lowering of the death rate of experimental animals at the early stage of intoxication by chlorofos at the prophylactic injection of the preparation, which, nevertheless, was not so significant, as in the case of intoxication by tetrachloromethane. Such fact allowed suggesting the existence of delayed unfavourable consequences for the organism (mutagenesis, cancerogenesis) as a result of the realization of the genotoxic action of chlorofos.

[Laser correlational spectroscopy in studying the subfractional composition of the blood plasma of patients with gastric hemorrhage, craniocerebral trauma and intoxication]. / Lazernaia korreliatsionnaia spektroskopiia v issledovanii subfraktsionnogo sostava plazmy krovi bol'nykh s zheludochnym krovotecheniem, cherepno-mozgovoi travmoi i intoksikatsiiami.

LCS presents information on the size distribution of particles in analysed objects. LCS of blood plasma was performed in 26 patients with stomach bleedings, 19 with brain injuries, 13 with chronic hepatitis, 149 with chronic chlorophos intoxication and 45 healthy subjects. Spectra of blood plasma from patients with stomach bleeding differed significantly from those of healthy subjects. Spectra of blood plasma from patients with brain injuries differed from those of alcohol poisoning patients. The size distribution of particles in the blood plasma alcohol poisoning patients was similar to that of the patients with chronic hepatitis or chronic chlorophos intoxication perhaps because of liver function disturbances in all these cases. These results allow LCS to be offered as a diagnostic method.

[Structural reorganization and change in the lipid composition of rat liver microsomes in chlorophos poisoning]. / Strukturnye perestroiki i izmenenie lipidnogo sostava mikrosom pechenie krys pri intoksikatsii khlorofosom.

The influence of chlorophos on the endoplasmatic reticulum of rat liver has been studied using the methods of gas-liquid chromatography and fluorescence. Experiments have demonstrated an increase of lysophosphatidylethanolamine, total phospholipids, unsaturated fatty acids (C20:4 n6, C18:1 n11, C18:1 n7) and a decrease of phosphatidylserine and phosphatidylethanolamine. Changes in microviscosity and surface charge were also shown.

[The role of endogenous K+ in realizing the protective action of M-cholinolytics in chlorophos poisoning]. / Rol' éndogennogo K+ v osushchestvlenii zashchitnogo deistviia M-kholinolitikov pri otravlenii khlorofosom.

The protective effect of M-cholinolytics during the poisoning of mice with chlorophos or exogenous acetylcholine is characterized by certain specific features. An attempt to reproduce the cholinolytic effect during poisoning by organophosphorus compounds was successful in case where the intoxication by a direct cholinomimetic was carried out in the presence of KCl solution or where the animals' poisoning was preceded by administration of voltage-dependent K+ channel blockers. The conclusion is made that the increased concentration of extracellular K+ occurring as the result of poisoning with organophosphorus compounds may play a role in the mechanism of the protective action of M-cholinolytics in chlorophos poisoning.