Oral Intoxication Research Articles

A technology of experimental studies on the xenobiotic element sorption characteristics of representatives of the intestinal normal flora

Modern views on the general level of intoxication of an organism by heavy metals are based solely on the extent of effects on organs and organ systems of macroorganisms while the impacts on representatives of the normal flora and their role in the organism’s mechanisms of detoxification as a whole are not taken into account. We proposed technology of experimental studies based on a complex variety of methods. The technology allows estimating the degree of effects of xenobiotic elements on representatives of the intestinal normal flora and their sorption characteristics, which is an important factor in the assessment of mechanisms of detoxification in oral intoxication. The obtained experimental data indicate high sorption characteristics of lead cations in the studied microorganisms, which, in our view, is primarily associated with microorganisms’ mechanisms of detoxification. The study found that the most pronounced bioaccumulative characteristics for lead were registered in Escherichia coli (65% of the total volume of the elements introduced in the substrate) and, in the case of cadmium, – Enterococcus faecium (33.2%). The minimal accumulation scores were revealed for Lactobacillus acidophilus (42.3% and 5.3%, respectively).

Unintentional cannabis intoxication in young children: Toward a standardized procedure for biological monitoring and follow-up?

Marijuana is the most commonly used illicit drug in France among diverse social circles. According to the ANSM report published in 2018, hospitalization of young children following cannabis exposure keeps increasing while concentration of Δ-9-tetrahydrocannabinol (THC) is higher and child poisoning with cannabis is more severe than ever. The effects of long-term THC exposure or recurrent intoxication during childhood may not be immediately perceptible and are poorly described in the literature. We reviewed poisoning conditions, diagnosis and monitoring of unintentional cannabis intoxication in children in order to suggest a standardized procedure for biological monitoring and follow-up. We conducted a retrospective observational study of admissions from 2010 to 2018 in the paediatric department at the University Hospital of Rouen. All children < 10 years old who were admitted to pediatric emergency with proven cannabis intoxication according to a rapid urine-screening test were considered. Thirty-three children were included and more than 70% were younger than 2 years old. Most cases were caused by accidental resin oral ingestion (85%) and intoxications were more frequently found in a family context (75%). Less than half of parents reported unintentional cannabis ingestion on arrival to emergency. Thirty children presented at least one acute neurologic symptom, 34% ophthalmological symptoms and less suffering from respiratory and cardiovascular impairment. All of them were hospitalized at least 24 h. Six of them underwent a lumbar puncture and one received intravenous antibiotics and antivirals. Only 12 quantitative blood tests using liquid chromatography-tandem mass spectrometry were performed. Only 30% of children were subject to a follow-up few months later. Three monitoring were performed by HPLC-MS/MS in hair samples, 7 in urines and one child had twice quantitative blood test. These data demonstrate a great variability in the biological management and follow-up according to prescribers who are not always well informed about the methodologies available. Clinicians should be careful about cannabis intoxication, especially concerning young children admitted in emergency units with unexplained neurological symptoms. We suggest a helping chart for biological diagnosis and monitoring, relying on the parent's good faith about their children cannabis ingestion. It includes hair, urine and blood analysis. The parents’ drug history (either therapeutic or recreational) should be investigated to avoid unnecessary and invasive tests and treatments. After initial diagnosis, the tests should usually include a quantitative blood test for the determination of THC and its metabolites to evaluate the severity of the intoxication and a plasma or blood bank should be stored for any further analysis. Furthermore, voluntary poisoning must be considered, especially if recurrent intoxication occurs. Depending on results, repeated hair analysis, toxicological screenings in blood and/or urines may be required several months later and may be reportable to a subsequent child protective services report. Nevertheless, recent data highlight some limits of hair sampling to discriminate acute from chronic exposure in children under 3 years old [1] . Cannabis intoxication in young children is becoming a more common problem and this report highlights the need to standardize procedures for biological monitoring and follow-up.

Dose-related impacts of imidacloprid oral intoxication on brain and liver of rock pigeon (Columba livia domestica), residues analysis in different organs

Available data regarding Imidacloprid (IMI) insecticide hazards to birds are still being scare. Our study aimed to investigate toxic impacts of IMI oral gavage by different dose levels on the brain and liver of Rock pigeon (Columba livia domestica). Forty mature male birds were divided equally into four groups. A control group (C) was orally dosed Mazola corn oil and other three groups; the low dose (LD), the medium dose (MD), and the high dose (HD) groups were orally dosed IMI in Mazola corn oil by three dose levels corresponding to 1/15th, 1/10th, 1/5th IMI oral LD50 respectively. IMI exposure induced a significant decrease in serum levels of glutathione (GSH), superoxide dismutase (SOD) enzyme activity. On the other hand; malondialdehyde (MDA) levels were elevated. The levels of serum total protein, albumin, globulin, and A/G ratio showed a non-significant changes in all IMI dosed groups except levels of total protein in the HD IMI dosed group showed a significant decrease compared to the C group. Serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid, plasma tumor necrosis factor α (TNFα) and plasma acetylcholinesterase (AChEs) enzyme activities showed a significant dose related increase in all IMI exposed groups compared to the C group; except the levels of ALT, LDH, and uric acid showed a non significant decrease in the LD IMI dosed group only. Residues of IMI were detected in the pectoral muscles, liver, brain, and kidney of all dosed rock pigeon. Moreover; pectoral muscles were the highest tissue for IMI residues detection. This is the first study reports accumulation of IMI in tissues other than crop, liver, and kidney of rock pigeon including brain and muscles. Moreover, the examined brain and liver tissues of all IMI dosed groups showed dosed related alterations in their structural and ultra-structural morphology. It is concluded that IMI oral administration to pigeon induced oxidative stress and detrimental effects in brain and liver of exposed pigeons. Additionally; IMI bio-accumulated in different organs being muscles is the highest tissues for IMI residues, thus monitoring of IMI residues in food is very essential.

Metal-Organic Frameworks as Efficient Oral Detoxifying Agents.

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (<9% degradation), poor intestinal permeation, and safety.

Identifying exposures to ribosome-inactivating proteins in blood samples: amplification of ricin-induced ribosomal damage products enables sensitive detection of active toxin and circulating depurinated 28S rRNA

Ricin, a highly potent plant-derived toxin, operates by site-specific depurination of ribosomes, which in turn leads to protein synthesis arrest. Recently, we presented the TRISOL [Truncated RNA Identification by Synthetic Oligonucleotide Ligation] method for the highly sensitive detection of exposures to type II ribosome-inactivating proteins such as ricin in clinical samples, based on the specific amplification of truncated cDNA molecules formed on ricin-dependent depurinated 28S rRNA templates. In the present study, we demonstrate the application of the TRISOL method to detect ricin exposure in blood samples. Sera collected from ricin-intoxicated animals was tested for the presence of either active ricin or ricin-induced depurinated 28S rRNA. Active ricin in serum samples from mice intranasally or intraperitoneally exposed to ricin was detected by the TRISOL method following incubation with a ribosomal-rich reticulocyte lysate preparation. For the detection of depurinated 28S rRNA in the serum, cell-free RNAs were isolated from the sera of mice and pigs at different time points following ricin intoxication by different exposure routes and analyzed for the presence of depurinated 28S rRNA. The TRISOL method allowed sensitive detection of both active ricin and host ribosomal damage in blood samples. Active ricin was detected at both early and late time points after ricin intoxication by all routes of exposure tested. Depurinated 28S rRNA, detected at later time points after systemic and oral intoxications, enables the determination of ricin-induced damage to cells of the exposed subject.

Brain MRI Findings in Tramadol Poisoning

Introduction: Recently tramadol intoxication and non-therapeutical abuse have been prevalent in Iran. in this study we aimed at evaluating possible central neural system lesions in patients with tramadol induced seizure by using MRI imaging.Methods & Materials: a cross-sectional study was conducted with age- and sex-matched case and control groups. The case group included oral tramadol intoxication cases with loss of consciousness and/or tramadol induced seizure. The control group included patients with seizure without tramadol consumption. In the first post seizure 24-hour, brain MRI was done and the images were interpreted by a radiologist. Finally all data were collected and they were recorded and analyzed using SPSS software.Results: 15 patients (7 females and 8 males) were in the control group and 15 patients (3 females and 12 males) were in the case group with mean age of 22.27±6.54 and 21.93±4.57 years, respectively. 8 patients of case group and 3 patients of control group had abnormal evidences (hyper signal foci in white mtter) in brain MRI images; there were no significant difference between two groups (p=0.128). Lesions depth in MRI images of case group were equally in Subcortical and Deep parts of white matter (37.5%) and in 2 cases (25%) were observed in both parts. There was no difference between two groups in this way (p=0.721). The most common involved lobe in both groups was frontal lobe which was observed in 62.5% (5 patients) of case group and 100% (3 patients) of control group. In comparison between two groups there was no significant difference in involved lobe (p=0.509).Conclusion: In our study, over half of case group patients had hypersignal evidences in MRI imaging. However no specific pattern was seen in these lesions. Also no significant difference was observed between case and control groups in lesions pattern.

Impact of oral cadmium intoxication on levels of different essential trace elements and oxidative stress measures in mice: a response to dose.

The study evaluated the effect of oral intoxication of cadmium and the possible causes of oxidative stress and its preferential accumulation in different organs as well as sub-sequential effects in mice. Twenty-four Swiss albino male mice were divided into three groups viz., normal control group without cadmium chloride (CdCl2), whereas a daily dose of 0.5 and 1.2mg of CdCl2 was orally administered for a period of a week to dose group 1 (DG-1) and dose group 2 (DG-2), respectively. A significant increase in the severity of cadmium toxicity was observed in animals as evidenced by aggravation in liver enzymes viz., serum alanine aminotransferase and aspartate transaminase, whereas lower levels of antioxidative stress markers in liver and kidney tissues of treated mice were observed as compared to normal control group. A significant depletion of calcium levels in liver tissues of DG-1 (217.36 ± 1.73μg/g of wet tissues) and DG-2 (186.41 ± 1.56μg/g of wet tissues) groups, along with Cd accumulation, was observed. To summarize, the current study would increase our understanding with respect to dose-dependent absorption of Cd and its toxicity led to mortality as well as adverse health effects in the body of mice. Graphical abstract ᅟ.

The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein

Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening disease botulism. They are naturally produced by species of the bacteria Clostridium botulinum as stable and non-covalent complexes, in which the BoNT molecule is assembled with several auxiliary non-toxic proteins. Some BoNT serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced by Clostridium strains that carry the ha gene cluster, which encodes four neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an important role to deliver and protect BoNTs in the gastrointestinal tract during oral intoxication. In contrast, BoNT/E- and BoNT/F-producing strains carry a distinct gene cluster that encodes five proteins (NTNHA, P47, OrfX1, OrfX2, and OrfX3, termed the orfX cluster). The structures and functions of these proteins remain largely unknown. Here, we report the crystal structure of P47 resolved at 2.8 Å resolution. Surprisingly, P47 displays a structural topology that is similar to bactericidal/permeability-increasing (BPI) like proteins, which were previously identified only in eukaryotes. The similarity of a hydrophobic cleft of P47 with the phospholipid-binding groove of BPI suggests that P47 might be involved in lipid association to exert its function. Consistently, P47 associates and induces aggregation of asolectin-containing liposomes in a protein- and lipid-concentration dependent manner. These findings laid the foundation for future structural and functional studies of the potential roles of P47 and OrfX proteins in facilitating oral intoxication of BoNTs.

Ранняя диагностика острого повреждения почек у детей с пероральными отравлениями химической этиологии

Ранняя диагностика острого повреждения почек у детей с пероральными отравлениями химической этиологии

Preparation and in vitro evaluation of hydrophobic‐modified montmorillonite stabilized pickering emulsion for overdose acetaminophen removal

AbstractPickering emulsion stabilized with hydrophobic‐modified montmorillonite (HMMT) was proposed for treating acute overdose acetaminophen intoxication, with a rapid removal rate, better stability, and good biocompatibility. The tiny HMMT was able to adsorb at the oil‐water interface of the Pickering emulsion to reduce the interfacial energy along with the formation of solid particle layer, in order to enhance the stability of the emulsion and improve the removal performance. With a fast removal rate, the detoxifying Pickering emulsion removed 0.5 g/L acetaminophen in the simulated gastric fluid to 0.13 g/L in 6 min, which is less than the intoxication content of 0.15 g/L, with a leakage ratio of lower than 4 % in simulated intestinal fluid over 4 h. Such a detoxifying emulsion was prepared at 55 °C with 2 % organoclay (HMMT) as the emulsifier, 6 % tributyl phosphate (TBP) as the extractant, and 0.1 mol/L NaOH as the inner phase in the volume ratio of 5:7. All the results denoted that the Pickering emulsion could be a promising candidate for the acute oral intoxication treatment.

Lethal Gastric Mucosal Necrosis due to Administration of Oral Ferrous Bisglycinate Chelate to Suckling Piglets

The oral application of a newly developed ferrous bisglycinate paste for suckling piglets at a dose of 180mg/kg body weight led to increased death rates in 10% (n=10) of Swiss test pig breeding farms (n=100). Necropsy examination of suckling piglets (n=12), selected randomly from the test farms with increased death rates, demonstrated severe gastric mucosal ulceration and necrosis. Due to the presence of crystalline iron surface coating within the gastric lesions, the iron was considered as the toxic principle and cause of death. To demonstrate the direct toxicity of ferrous bisglycinate, the paste was administered experimentally to a litter of suckling piglets (n=11). Different time points (24, 48 and 72h post partum) and doses (180mg/kg and 360mg/kg) were investigated. The manufacturer's recommended dose of 180mg/kg corresponded to approximately 36mg Fe/kg and to 6.4 % of the acute lethal dose50 of oral iron in rats. In all piglets the lesions were reproduced and most severe at the earliest time point (24h post partum) and with the highest applied dose (360mg/kg). The lesions were in accordance with those described from oral iron intoxication in man, suggesting pigs as an ideal animal model for oral iron toxicity studies.

Treating Prey With Glyphosate Does Not Alter the Demographic Parameters and Predation of the Harmonia axyridis (Coleoptera: Coccinellidae).

Glyphosate is an herbicide that is used worldwide with potential environmental risks to nontarget organisms. We applied an age-stage, two-sex life table approach to assess the sublethal effects of short-term oral exposure to a glyphosate-based herbicide on the life table parameters and biocontrol potential of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae). Aphids (Metopolophium dirhodum (Walker) (Sternorrhyncha: Aphididae)) treated with herbicide (an isopropylamine-salt of glyphosate) at low recommended, maximum recommended, and double the maximum recommended concentration for agricultural situations, and untreated controls were offered to the fourth instar of H. axyridis for 24 h. Development, consumption, and fecundity were measured daily until death. We detected minor differences in the hatching rate and mean generation time, whereas the longevity, fecundity, net reproductive rate, intrinsic rate of increase, finite rate of increase, and consumption were unaffected across treatments. We conclude that biocontrol potential of H. axyridis was not affected by acute oral intoxication by a glyphosate-based herbicide during the larval stage for 24 h under the study design.

Postmortem Computed Tomographic Analysis of Death Caused by Oral Drug Intoxication

Traditional autopsy has changed little in the past century. In Japan, the rate of forensic autopsy in cases of unusual death is very low. Therefore, multi-slice computed tomography (CT) has been used to obtain imaging data instead of or in addition to autopsy in suspicious forensic cases. In our institute, postmortem multi-slice CT has been performed since 2009, and by 2014 there were over 1,000 cases. Our extensive experience with postmortem CT shows that in many cases of death by drug overdose, stomach contents exhibit high X-ray absorption. This article reviews the relationship between CT findings of stomach contents and toxicological analysis results in 23 cases of death by drug overdose. All cases (12 females and 11 males, aged 44 ± 11 years) known to have orally ingested drugs were included in this study. We assessed the slices of all stomach areas on consecutive axial CT images. Twenty cases (87%) showed high X-ray absorption in the stomach, while the other three did not demonstrate radio-dense stomach contents even though drug analysis detected lethal concentrations of drugs in the blood. In conclusion, drugs were frequently, but not always, visualized as contents with high X-ray absorption in the stomach. Postmortem gastric CT images can provide useful information in cases of oral drug intoxication if there are empty drug packages or a suicide note at the death scene. However, precise determination of the cause of death requires full autopsy in cases where there is no indication of suicide at the death scene.

The forensic medical evaluation of traumatic and spontaneous ruptures of the organs affected by the tumours

The present article was designed to report the results of the analysis of the cases of traumatic and spontaneous ruptures of the organs affected by the tumours based on the original observations and the literature data. It is shown that the probability of the tumour rupture depends on its histological type, localization, the size, and the distance from the capsule of the affected organ, the degree of involvement of the major blood vessels, the severity of the necrotic changes, the presence of cysts in the neoplasm, and the regimens of radio- and chemotherapy. Moreover, the rupture can be facilitated by anticoagulation therapy, intake or oral contraceptives, pregnancy, concomitant diseases, alcoholic intoxication, splenomegaly, and hypocoagulation resulting from dissemination of the neoplastic process or the metastatic lesions of the liver. Even a minimal injury to the skin can provoke the tumour rupture associated with the fatal hemorrhage. A delayed rupture within a few hours or days is possible.

Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A.

Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies.

A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response.

Ricin activates the proinflammatory ribotoxic stress response through the mitogen activated protein 3 kinase (MAP3K) ZAK, resulting in activation of mitogen activated protein kinases (MAPKs) p38 and JNK1/2. We had a novel zak−/− mouse generated to study the role of ZAK signaling in vivo during ricin intoxication. To characterize this murine strain, we intoxicated zak−/− and zak+/+ bone marrow–derived murine macrophages with ricin, measured p38 and JNK1/2 activation by Western blot, and measured zak, c-jun, and cxcl-1 expression by qRT-PCR. To determine whether zak−/− mice differed from wild-type mice in their in vivo response to ricin, we performed oral ricin intoxication experiments with zak+/+ and zak−/− mice, using blinded histopathology scoring of duodenal tissue sections to determine differences in tissue damage. Unlike macrophages derived from zak+/+ mice, those derived from the novel zak−/− strain fail to activate p38 and JNK1/2 and have decreased c-jun and cxcl-1 expression following ricin intoxication. Furthermore, compared with zak+/+ mice, zak−/− mice have decreased duodenal damage following in vivo ricin challenge. zak−/− mice demonstrate a distinct ribotoxic stress–associated phenotype in response to ricin and therefore provide a new animal model for in vivo studies of ZAK signaling.

Characterization of a Mouse Model of Oral Potassium Cyanide Intoxication.

Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9.9 mg/kg in water for adult male, adult female, juvenile male, and juvenile female mice, respectively. The time to death was rapid and dose dependent; juvenile mice had a shorter mean time to death. Juvenile mice displayed a more rapid onset and higher incidence of seizures. The time to observance of respiratory signs and prostration was rapid, but mice surviving beyond 2 hours generally recovered fully within 8 hours. At doses up to the LD50, there were no gross necropsy or microscopic findings clearly attributed to administration of KCN in juvenile or adult CD-1 mice from 24 hours to 28 days post-KCN challenge. Toxicokinetic analysis indicated rapid uptake, metabolism, and clearance of plasma cyanide. Potassium cyanide caused a rapid, dose-related decrease in blood pH and increase in serum lactate concentration. An increase in fatty acid-binding protein 3 was observed at 11.5 mg/kg KCN in adult but not in juvenile mice. These studies provide a characterization of KCN intoxication in adult and juvenile mice that can be used to screen or conduct preclinical efficacy studies of potential countermeasures.

ASSESSMENT OF ACUTE POISONING AMONG CHILDREN IN DAMIETTA GOVERNORATE

Background: Unintentional toxicology represented an important health problem in pediatrics. However, there was no appropriate map helping in design of proper preventive strategies. Objective: Investigating the pattern of acute toxicity of children aged 1–18 years in Damietta governorate. Subjects and methods: The study included children presented to Emergency Department of Damietta Poison Control Center (PCC) during the period from January 2015 to December 2015. In all children, the following parameters were studied: mean age, sex, residence, occupation, route of exposure, manner of poisoning, time elapsed between exposure to toxin and hospital arrival, past medical history, family history, seasonal distribution, admission place (ED, inpatient, ICU, or referral); and outcome (Improvement, referral and death). Clinical and Investigational aspect of the study included general examination, systemic examination and investigations (laboratory, ECG, Plain chest X-ray, Plain abdominal X-ray, CT and/or MRI in cases of coma or unexplained etiology). Curative aspect of the study included emergency measures, decontamination, enhancement of elimination, and administration of specific therapy). Results: There was a statistically significant difference between studied groups as regard gender distribution. Residence was rural in 78.4% and urban in 21.6%. The most common toxic agent(s) were insecticides (46.6%), hydrocarbons (24.1%), corrosives (19.8%) and medicinal agents (9.5%). The toxicity was mild in majority of children (72.4%), and the severity of toxicity increased with increasing age. The delay time was less than an hour in the majority of children (58.6%). The oral route was the most common (69.0%) and oral route intoxication increased with increasing age. Intoxication was accidental in the majority of studied children (84.5%) and no suicidal cases below the age of 6 years. Location of toxicity in studied children was home in the majority of subjects (84.5%) and outside home (15.5%), with a statistically significant difference between them. Outcome revealed that 30.2% and 69.8% were discharged from Emergency Department. The discharge rate from Emergency Department decreased with increasing age. Conclusion: The present study provided a road map for the pattern of childhood toxicity in Dameitta governorate. It is the first step to explore the magnitude of the problem in this area of Egypt. Future efforts are needed to complete the map with development of effective preventive strategies.

Orale ivermectine-intoxicatie op een vleeskalverbedrijf

In deze casus wordt een vermoedelijk kwaadwillige, orale ivermectine-intoxicatie op een Vlaams vleeskalverbedrijf besproken. Alle 330 kalveren van twee tot vier weken oud werden in de eerste week na aankomst op het bedrijf getroffen. De symptomen waren ernstige depressie, het neerliggen in laterale of sternale positie, tremor en kopschudden. Uiteindelijk stierf 13,6% van de kalveren. De overige dieren herstelden gradueel met ondersteunende orale rehydratatietherapie over een termijn van vijf tot zeven dagen. In de kunstmelk kon een ivermectinegehalte van 35 mg/kg aangetoond worden. In het serum van drie kalveren werden ivermectinegehaltes van 0,75 mg/kg tot 1,1 mg/kg gevonden. De vermoedelijk toegediende dosering was 1,75 mg/kg lichaamsgewicht voor een gemiddeld kalf (40 kg). In deze casus wordt aangetoond dat orale toxiciteitsverschijnselen van ivermectine bij kalveren van twee tot vier weken oud kunnen optreden aan een dosis die 8,75 keer hoger is dan de geregistreerde therapeutische dosis voor subcutane toediening bij rundvee.

Shiga Toxin (Stx) Type 1a Reduces the Oral Toxicity of Stx Type 2a.

Background. Shiga toxin (Stx) is the primary virulence factor of Stx-producing Escherichia coli (STEC). STEC can produce Stx1a and/or Stx2a, which are antigenically distinct. However, Stx2a-producing STEC are associated with more severe disease than strains producing both Stx1a and Stx2a.Methods and Results. To address the hypothesis that the reason for the association of Stx2a with more severe disease is because Stx2a crosses the intestinal barrier with greater efficiency that Stx1a, we covalently labeled Stx1a and Stx2a with Alexa Fluor 750 and determined the ex vivo fluorescent intensity of murine systemic organs after oral intoxication. Surprisingly, both Stxs exhibited similar dissemination patterns and accumulated in the kidneys. We next cointoxicated mice to determine whether Stx1a could impede Stx2a. Cointoxication resulted in increased survival and an extended mean time to death, compared with intoxication with Stx2a only. The survival benefit was dose dependent, with the greatest effect observed when 5 times more Stx1a than Stx2a was delivered, and was amplified when Stx1a was delivered 3 hours prior to Stx2a. Cointoxication with an Stx1a active site toxoid also reduced Stx2a toxicity.Conclusions. These studies suggest that Stx1a reduces Stx2a-mediated toxicity, a finding that may explain why STEC that produce only Stx2a are associated with more severe disease than strains producing Stx1a and Stx2a.