Stages Of Intoxication Research Articles

ОБ ОЦЕНКЕ ВЛИЯНИЯ АЛКОГОЛЬНОЙ ИНТОКСИКАЦИИ НА ПАРАМЕТРЫ ГОЛОСА В СИСТЕМАХ БИОМЕТРИЧЕСКОЙ АУТЕНТИФИКАЦИИ

Changing the voice characteristics of a person under the influence of alcohol intoxication affects the effectiveness of the identification procedure. From which it follows that the determination of the level of alcohol in the blood remotely is important for ensuring information security in computer systems. The purpose of the present paper is to analyze the existing voice authentication methods and approaches to improve accuracy, analyze existing data sets, and evaluate the influence of the psychophysiological state of the speaker on the parameters of his speech. The focus of this study is on exploring different approaches to recognizing alcohol intoxication and evaluating their effectiveness. The study includes a comparative analysis of these methods, emphasizing the importance of using a comprehensive and representative data set that takes into account factors such as gender, age, stage of intoxication, recording quality, and ambient noise levels. Based on the analysis of scientific publications, the study identifies the random forest method as one of the most effective machine learning methods, demonstrating an accuracy of 95.3% for all speech datasets and 80% for the widely used Alcohol Language Corpus.

Proteome Analysis of Whole-Body Responses in Medaka Experimentally Exposed to Fish-Killing Dinoflagellate Karenia mikimotoi.

Karenia mikimotoi is a well-known harmful algal bloom species. Blooms of this dinoflagellate have become a serious threat to marine life, including fish, shellfish, and zooplanktons and are usually associated with massive fish death. Despite the discovery of several toxins such as gymnocins and gymnodimines in K. mikimotoi, the mechanisms underlying the ichthyotoxicity of this species remain unclear, and molecular studies on this topic have never been reported. The present study investigates the fish-killing mechanisms of K. mikimotoi through comparative proteomic analysis. Marine medaka, a model fish organism, was exposed to K. mikimotoi for a three-part time period (LT25, LT50 and LT90). Proteins extracted from the whole fish were separated by using two-dimensional gel electrophoresis, and differentially expressed proteins were identified with reference to an untreated control. The change in fish proteomes over the time-course of exposure were analyzed. A total of 35 differential protein spots covering 19 different proteins were identified, of which most began to show significant change in expression levels at the earliest stage of intoxication. Among the 19 identified proteins, some are closely related to the oxidative stress responses, energy metabolism, and muscle contraction. We propose that oxidative stress-mediated muscle damage might explain the symptoms developed during the ichthyotoxicity test, such as gasping for breath, loss of balance, and body twitching. Our findings lay the foundations for more in-depth studies of the mechanisms of K. mikimotoi’s ichthyotoxicity.

Интоксикации ртутью в бытовых и производственных условиях

Ртуть — жидкий серебристо-белый тяжелый металл. Ртуть принадлежит к промышленным ядам первого класса опасности. В организм ртуть проникает в основном через органы дыхания, реже — через кожу. Эти пути ее поступления в организм вызывают интоксикации. Возможно также попадание ее и через органы пищеварения. В этом случае интоксикация не развивается. Выделяется ртуть с мочой, калом, потом, слюной и молоком матери во время лактации. Ртуть принадлежит к группе тиоловых ядов и блокирует сульфгидрильные группы белковых соединений. Ртуть нарушает белковый обмен и ход ферментативных процессов. Все это приводит к глубоким нарушениям в функционировании центральной нервной системы, особенно ее высших отделов. Различают острые и хронические формы интоксикации ртутью. Острая интоксикация развивается бурно. В развитии хронической интоксикации выделяют три стадии: начальную (функциональную), умеренно выраженных изменений и выраженную. Диагноз основывается на типичной клинической картине, данных профессионального анамнеза и санитарно-гигиенической характеристике условий труда. Подтверждением диагноза является наличие ртути в моче при клинических признаках интоксикации. Наиболее эффективным антидотом при интоксикациях, вызванных ртутью, является унитиол. Эффективны также натрия тиосульфат и сукцимер. На начальной стадии интоксикации рекомендуется временное, на 1–2 месяца, прекращение контакта с ртутью и другими токсичными веществами. Проводится соответствующее лечение. При улучшении состояния рабочий может возвратиться к предыдущей работе при условии тщательного врачебного наблюдения за состоянием его здоровья. В выраженной стадии интоксикации дальнейшая работа в условиях влияния ртути противопоказана. Больному требуется перевод на работу, которая не связана с влиянием любых токсичных веществ. Его направляют на медико-социальную экспертную комиссию для установления степени потери трудоспособности. Главная задача профилактики интоксикаций, вызванных ртутью, состоит в замене ртути менее вредными веществами, снижении концентрации ее паров в воздухе рабочей зоны. Проводятся автоматизация и герметизация производственных процессов. Помещения, в которых выполняются работы с ртутью, должны быть оборудованы непроницаемыми для ртути стенами и полом и обеспечены эффективной вентиляцией. Лица, которые работают с ртутью, обеспечиваются специальной одеждой из плотной ткани. Проводятся предварительные и периодические медицинские осмотры.

Where and What You Drink Is Linked to How Much You Drink: An Exploratory Survey of Alcohol Use in 17 Countries

Background This paper aimed to explore the differences in subjective experiences of intoxication depending on drinking location and drink type. Methods: Data came from 32,194 respondents to The Global Drug Survey (GDS) 2015, an annual, cross-sectional, online survey. Respondents selected their usual drinking location (home alone: home with partner/family: house parties: pubs/bars or clubs) and usual drink (wine; beer/cider/lager; spirits or alcopops/coolers). They indicated how many drinks they required to reach three stages of intoxication (feeling the effects; an ideal stage of intoxication; and the tipping point) and how frequently they reached each stage. Results: Drink type affected grams of alcohol reported to reach the tipping point: 109 gm wine, 127 gm alcopops, 133 gm of beer, and 134 gm of spirts. Respondents who drank at home alone, or in clubs reached their tipping point more frequently compared to other locations. Conclusions: Where people drink, and the type of alcohol they drink, affected the amount of alcohol reported to reach different stages of intoxication. Understanding why different drinking locations, and drink types lead to a need for greater consumption to reach an ideal state of drunkenness, such as social cues from other people who drink, may enable people to reduce their drinking.

INTENSITY OF NITRIC OXIDE SYNTHESIS IN THE BLOOD OF RATS UNDER THE INFLUENCE OF SODIUM FLUORIDE

The influence of fluoride ion as a chemical agent affects the metabolism, the change of which is manifested in functional and structural changes. The final stable metabolites of NO include nitrite and nitrate anions (NO2, NO3), the concentration of which serves as an indirect method for estimating the intensity of NO synthesis. The concentration of NO is a major factor in its numerical biological effects (regulatory, protective). At low NO concentrations, direct effects aimed at maintaining homeostasis, such as the vascular, respiratory, and nervous systems, predominate; at high concentrations of NO, indirect effects prevail, due primarily to the formation of peroxynitrite. It is known that when the rate of free radical reactions in the body increases, NO can react with a superoxide anion radical to form peroxynitrite, a highly reactive compound with destructive properties against proteins and lipids. Oral administration of FN to rats in doses of 1/10 and 1/100 DL50 leads to an increase in the content of nitrite and nitrate anions in the blood plasma during the first 30 days, which indirectly indicates excess production of nitric oxide, which in the initial stages of intoxication may play a compensatory role, but subsequently cause pathological reactions associated with the activation of oxidative stress. The decrease in nitrite and nitrate anions at the end of long-term action of FN indirectly indicates a decrease in nitric oxide generation, which may be associated, in particular, with an increase in peroxynitrite concentration due to the use of nitric oxide in reaction with superoxide anion radical and antioxidant deficiency.

Preventing and Mitigating Alcohol Toxicity: A Review on Protective Substances

This review covers three fundamental aspects of alcohol consumption and research efforts around the prevention and mitigation of its toxic effects in the human body. First, the sociocultural aspects of alcohol consumption are analysed, including drinking habits and strategies to combat intoxication. Second, we briefly introduce the biochemical aspects of ethanol metabolism and the biochemical pathways leading to its degradation, particularly the activation of toxic response pathways. Finally, we review current evidence and research efforts for finding compounds and substances able to prevent and mitigate the toxic effects of alcohol when over-indulgence has occurred. The toxic effects appear as a time-evolution process based on the stage of intoxication. We explore different compounds and formulations traditionally used to combat alcohol toxicity, as well as state-of-the-art research in the topic for novel molecules and formulations. Although we aimed to categorise which compounds are more effective for a particular level of alcohol intoxication, it is impossible to fully prevent or mitigate toxicity effects by only the compounds in isolation, further research is required to establish the long-term prevention and mitigation from the clinical point of view.

Therapeutic plasma exchange in treating multi-organ injury at the later stage of mushroom poisoning: Three case reports

Ingestion of Amanita phalloides, a deadly wild mushroom, can cause multi-organic injury. The value of therapeutic plasma exchange (TPE) in treating mushroom poisoning was controversial, especially for those patients at the later stage. We reported three cases of acute liver injury, coagulopathy, and hepatic encephalopathy secondary to mushroom poisoning at the later stage. Therapeutic plasma exchange (TPE) session was repeated 2~5 times depending on the patients’ conditions. Pathological plasma ranging from 1600 to 1800 mL was exchanged for each session with fresh frozen plasma and normal saline based on the patients’ body weight. Patients’ liver function, coagulation function, and clinical symptoms were immediately improved upon TPE treatment. TPE is a reliable therapy for patients with acute liver injury, coagulopathy, and hepatic encephalopathy secondary to mushroom poisoning at the later stage of poisoning.

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning

Context. Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances. Case details. A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually. Conclusion: We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.

Neurotrophic factors concentration in rat brain at the experimental coma

Aim. To study the changes of neurotrophic factors concentrations depending on stage of intoxication with deprivation substances (ethanol or sodium oxybutirate) in rats. Methods. Experiments were performed on male white laboratory rats. Control and experimental groups included 10 animals each. Half-lethal doses of a deprivation substance (ethanol or sodium oxybutirate) were introduced intraperitoneally 3, 6, 12, 24 and 72 hours before blood specimen collection. Neuron-specific enolase, S-100 protein, brain-derived neurotrophic factor, pigment epithelium-derived factor, glial fibrillary acidic protein serum levels were measured by enzyme immunoassay. Results. At single infusion of mean lethal dose of sodium oxybutyrate S-100 protein serum level significantly increased after 6 hours compared to control and stayed elevated during the first 24 hours. The levels of neurotrophic and neuroprotective factors also significantly increased 3 and 6 hours after the drug administration. The toxic dose of ethanol have significantly increased (over than 1.8 times compared to the controls) the concentration of protein S-100 in rats after 3 hours. The maximum increase in the protein S-100 level (by 2.6 times and over) was noted 12 hours after the toxicant administration. Glial fibrillar acidic protein concentration was 2.9 times higher compared to controls 3 hours after and 1.9 times higher 6 hours after higher the ethanol administration (р 0.05). The concentration of brain - derived neurotrophic factor has also increased from 3 to 12 hours after the toxicant administration, and was 2.1 to 2.4 times higher compared to intact animals. Conclusion. Studying of neurotrophic factors brain in plasma showed that the development of hypoxia, accompanying coma, leads to higher serum levels of S-100 protein, brain-derived neurotrophic factor and glial fibrillar acidic protein. The increase in the concentration of S-100 is a marker for the presence of brain damage. The observed increase of glial fibrillar acidic protein in experiments with ethanol may indicate its more severe brain tissue damage compared to sodium oxybutyrate.

Biochemical and Ultrastructural Changes in the Hepatopancreas ofBellamya aeruginosa(Gastropoda) Fed with Toxic Cyanobacteria

This study was conducted to investigate ultrastructural alterations and biochemical responses in the hepatopancreas of the freshwater snail Bellamya aeruginosa after exposure to two treatments: toxic cyanobacterium (Microcystis aeruginosa) and toxic cyanobacterial cells mixed with a non-toxic green alga (Scendesmus quadricauda) for a period of 15 days of intoxication, followed by a 15-day detoxification period. The toxic algal suspension induced a very pronounced increase of the activities of acid phosphatases, alkaline phosphatases and glutathione S-transferases (ACP, ALP and GST) in the liver at the later stage of intoxication. During the depuration, enzymatic activity tended to return to the levels close to those in the control. The activity of GST displayed the most pronounced response among different algal suspensions. Severe cytoplasmic vacuolization, condensation and deformation of nucleus, dilation and myeloid-like in mitochondria, disruption of rough endoplasmic reticulum, proliferation of lysosome, telolysosomes and apoptotic body were observed in the tissues. All cellular organelles began recovery after the snails were transferred to the S. quadricauda. The occurrence of a large amount of activated lysosomes and heterolysosomes and augment in activity of detoxification enzyme GST might be an adaptive mechanism to eliminate or lessen cell damage caused by hepatotoxicity to B. aeruginosa.

Fractal dimension values of cerebral and cerebellar activity in rats loaded with aluminium

Aluminium interferes with a variety of cellular metabolic processes in the mammalian nervous system and its intake might increase a risk of developing Alzheimer's disease (AD). While cerebral involvement even at the early stages of intoxication is well known, the role of cerebellum is underestimated. Our aim was to investigate cerebral and cerebellar electrocortical activity in adult male rats exposed to chronic aluminium treatment by nonlinear analytic tools. The adult rats in an aluminium-treated group were injected by AlCl(3), intraperitoneally (2 mg Al/kg, daily for 4 weeks). Fractal analysis of brain activity was performed off-line using Higuchi's algorithm. The average fractal dimension of electrocortical activity in aluminium-treated animals was lower than the average fractal dimension of electrocortical activity in the control rats, at cerebral but not at cerebellar level. The changes in the stationary and nonlinear properties of time series were more expressed in cerebral electrocortical activity than in cerebellar activity. This can be useful for developing effective diagnostic and therapeutic strategies in neurodegenerative diseases.

Bajiaolian poisoning—a poisoning with high misdiagnostic rate

Background One of the oldest Chinese herbal medicine, bajiaolian is widely used in traditional therapy. In Taiwan, bajiaolian is the fifth highest cause of poisoning among herbal medicines. The diagnosis is difficult because physicians are unfamiliar with this medicine's multiple presentations in different stages of intoxication. Procedures The records of 4 major poison centers in Taiwan were searched for all bajiaolian intoxication from July 1985 (the opening of first poison center) to March 2003. Two emergency physicians with toxicologic training reviewed the admission charts and visited case patients for follow-up. Findings Seventeen patients were identified, of which 15 (88.2%) had been misdiagnosed initially. In the beginning of their medical care, 14 cases were diagnosed as acute gastroenteritis. Conclusion Bajiaolian intoxication is probably misdiagnosed because of early gastrointestinal symptoms followed by neurologic symptoms. A detailed patient history should be taken, and symptoms should be reviewed systemically to improve diagnostic accuracy.

Mice liver protein synthesis in vivo and in vitro after cadmium chloride administration

Objective: To evaluate effects of cadmium ions on the protein synthesis in mice liver in vivo and in vitro. Methods: Experiments were done on white laboratory mice using i.p. injections of appropriate amounts of cadmium chloride solution. Protein synthesis or tRNA acceptor activity was evaluated by the incorporation of [ 14 C]-leucine into newly synthesized peptides and proteins or formation of aminoacyl-tRNA. Liver cell-free translation system was made on the basis of post-mitochondrial supernatant. Results: Single doses of Cd 2+ at the amounts equal to 0.025 LD 50 and 0.05 LD 50 (0.08 mg/kg and 0.16 mg/kg) do not have very significant impact on the protein synthesis in liver 24 h after the heavy metal administration. Only 0.5 LD 50 Cd 2+ (1.6 mg/kg) reduces protein synthesis by approximately one third. However, within 24 h after the intoxication with 0.5 LD 50 , cadmium revealed initial inhibition of translation within the first 2 - 4 h, which progressed into stimulation, reaching its maximum at the 8th h and subsequent decrease. In vitro cadmium at lower concentration (40 μM) demonstrated stimulatory effect on both measured parameters of translation -the rate and level, while sharp inhibition of protein synthesis began only at relatively high concentration of this heavy metal (above 60 pM). When treated in vivo, 0.5 LD 50 cadmium 2 h after injection reduced the acceptor activity of tRNA almost by 50%, but already 8 h after the injection acceptor activity of tRNA was back at the level of control. Cadmium chloride when added directly to the liver extracts of control animals displayed very strong inhibitory effect on the tRNA acceptor activity, which had linear dependence on the cadmium concentration. Conclusions: Cadmium induces significant fluctuations of liver protein synthesis at the early stages of intoxication in vivo, which includes both inhibition and stimulation. Cadmium significantly reduces the acceptor activity of liver tRNA both in vivo and in vitro.

Effects of lead on mice protein synthesis in vivo and in vitro

Objective: To evaluate effects of lead ions on the general protein synthesis in mouse organs in vivo and in liver cell-free translation system. Methods: Experiments were done on white laboratory mice using i.p. injections of appropriate amounts of lead acetate solution. Protein synthesis was evaluated by the incorporation of 14 C-labeled leucine into newly synthesized proteins. Liver cell-free translation system was made on the basis of post-mitochondrial supernatant. Results: Even a sublethal concentration of lead ions (0.5 LD 50 ) was not capable to yield major protein synthesis inhibition in mouse liver, kidneys, skeletal muscle and heart 24 h after the experimental intoxication. Further increase of lead ions up to 0.75 LD 50 significantly decreased protein synthesis in these organs (except the liver). However, we found that at earlier stages of intoxication (within initial 8 h), strong perturbations of protein synthesis occur in mouse organs; 0.5 LD 50 lead caused a significant stimulation of translation in liver and kidneys, which reached 202% in liver at 8th h and 175% in kidneys at 2nd h. Protein synthesis in skeletal muscle was both stimulated by 43% at 2nd h and suppressed by 36% at 8th h. Lead ions did not cause any severe fluctuations in the heart translation intensity; 48 h after the experimental intoxication protein synthesis in studied organs was as in norm. Data of experiments in vitro showed that lead ions at concentration up to 50 pM activate translation in liver cell-free protein-synthesizing system. This concentration is approximately 10-fold lower than that one needed to obtain stimulatory effect in vivo. Conclusions: Lead ions induce significant fluctuations of protein synthesis activity at the early stages of intoxication in vivo, which tend to become normalized with time. Lead at low concentration is capable to stimulate protein synthesis both in vivo and in vitro.

Assessing variation in alcohol outcome expectancies across environmental context: An examination of the situational-specificity hypothesis.

Using an in vivo manipulation, this study examined whether alcohol outcome expectancies (AOEs) vary across environmental settings. Two hundred twenty-one undergraduates were randomly assigned to 1 of 4 conditions in which environmental context (an on-campus bar vs. a laboratory) and instructed phase of intoxication ("just enough to begin to feel intoxicated" vs. "too much to drink") were manipulated. AOEs were assessed with a revised version of the Effects of Alcohol Scale (L. Southwick, C. Steele, A. Marlatt, & M. Lindell, 1981). Compared with participants tested in the laboratory, individuals exposed to the on-campus bar expected greater alcohol-related stimulation/perceived dominance and pleasurable disinhibition. Women expected more behavioral impairment during the latter stage of intoxication. These findings highlight the importance of ecologically valid research in this area, as well as cue-exposure assessment and treatment approaches.

Induction of autotomy in the American bird grasshopperSchistocerca americana (Drury) by the ecdysone agonist RH-5849 and investigation of its mode of action

The non-steroidal ecdysone agonist RH-5849 (1,2-dibenzoyl-l-tert-butylhydrazine) was found to be an effective neurotoxicant on injection into the American bird grasshopper,Schistocerca americana (Drury). Treated grasshoppers became immediately hyperactive, followed by loss of coordination, paralysis and eventually death. We also discovered that this compound induced bilateral autotomy of the metathoracic legs during the early stages of intoxication. However, no evidence of ecdysonergic or morphogenetic activities was observed. Synergism studies with neurotoxins of known mode of action suggested that RH-5849 has a mechanism of action similar to that of 4-amino pyridine, which blocks potassium channels.

Comparison of thermally oxidized lipids and acetaminophen with concurrent consumption of ethanol as inducers of liver cirrhosis

The mechanism(s) of liver damage initiated by ingestion of toxic components of thermally oxidized lipids was compared in a rat model with the documented mechanisms of hepatic failure and necrosis initiated by acetaminophen. Acetaminophen (50 mg/kg body weight) or oxidized lipids (0.15 ml oxidized trilinolein or 1.05 ml oxidized butter oil per rat) were intubated at 12-h intervals to rats. Treated rats were allowed free access to food and water containing 3% ethanol. Changes in relative concentration of acute-phase plasma proteins, determined by two-dimensional (2D) immunoelectrophoresis, were taken as a marker of liver damage. In contrast to simple inflammation, acute-phase plasma proteins in this study disproportionately increased or decreased as histological damage of the liver due to intubation oxidized lipids or acetaminophen. Histological examination of liver of rats intoxicated with oxidized lipids revealed severe liver cirrhosis at the end of the trial, where the remaining viable hepatocytes were separated in a matrix of collagen. [3H1]Thymidine incorporation in hepatic DNA of acetaminophen or oxidized lipid intoxication increased in the early stages of intoxication, indicative of regenerative activity of the liver. Further progression of the cirrhosis inhibited continued liver regeneration and [3H1]thymidine incorporation into hepatic DNA. The cirrhotic liver at this stage failed to regenerate to the original mass upon 75% partial hepatectomy. Therefore, it may be concluded that hepatic necrosis produced by oxidized lipids or by acetaminophen may have similar mechanisms.

Structural alterations of rat erythrocytes induced by phosphacol poisoning

Nembutal-anesthetized rats under conditions of artificial respiration received intramuscular injections of phosphacol in doses equal to 0.5, 5, and 50 LD50. The lung ventilation per se induced blood changes typical of hyperventilation alkalosis. Poisoned animals showed the development of dose-dependent tissue acidosis. At a later stage of poisoning (2 hours) a high phosphacol dose induced decompensated acidosis, which caused the death of some animals. Electron microscopy revealed that the previously described rat erythrocyte deformation coincides in time with the changes of cytoskeleton content and depends on the dose of phosphacol but not on the blood pH.

Effects of lithium carbonate administration to healthy cats

Summary Lithium carbonate administration to healthy cats was evaluated in 2 controlled studies (a dose-response study and a bone marrow evaluation study) to determine the effectiveness of lithium as a bone marrow stimulant. Lithium carbonate was administrated at dosage ranging from 300 to 1,050 mg/m2 of body surface/d. Complete blood count, serum lithium concentration determination, serum biochemical analysis, urinalysis, and bone marrow aspiration and biopsy were periodically performed. Serum lithium concentration > 2 mEq/L was associated with significant decrease in numbers of circulating segmented neutrophils (< 1,200 cells/μl; P < 0.01) and lymphocytes (< 1,300 cells/μl; P < 0.0001), as well as significant (P < 0.05) decrease in urine specific gravity. Bone marrow evaluation revealed apparent maturation arrest of the neutrophil cell line. Coincident with the changes in laboratory values, the lithium-treated cats became ill. Changes in behavior and vocalization were seen, followed by anorexia, vomiting, and diarrhea. In later stages of intoxication, cats became hyperexcitable and manifested coarse muscular tremors. It was concluded that lithium carbonate does not have potential value as a bone marrow stimulant and is toxic to cats at serum concentration > 2 mEq/L.

Distal terminal axonopathy produced by 2,4-dithiobiuret: effects of long-term intoxication in rats

It has been well established that 2,4-dithiobiuret (DTB) intoxication in rats produces a rapidly progressive hindlimb paralysis within days. The cause of this has, until recently, been explained on the basis of a physiological abnormality that involves a prejunctional impairment in the neuromuscular transmission alone. The morphological correlate of the electrophysiological abnormalities has now been provided. This study describes the sequential morphological alterations resulting from a chronic long-term DTB intoxication (1 mg/kg per day, IP) in the rat nervous system up to 48 days. The findings indicate that DTB neurotoxicity evolves as a central peripheral distal axonopathy initially affecting the motor nerve terminals which show accumulation of interconnecting branched tubulovesicular profiles. With continued exposure, nerve terminal swelling and degeneration took place. Similar pathological changes in distal axons were observed progressively involving the small intramuscular nerve bundles close to the nerve terminals. Central nervous system axons in the long descending tracts of spinal cord and the cerebellar vermis showed similar changes but to a lesser extent in later stage of intoxication.