Atrazine-induced environmental nephrosis was mitigated by lycopene via modulating nuclear xenobiotic receptors-mediated response.

The burden and morbidity of environmental nephrosis is increasing globally. Atrazine (ATR) and degradation products in the environment are considered key determinants of nephrosis. However, the lack of highly effective treatments for environmental nephrosis creates an urgent need to better understand the preventive strategies and mechanisms. This study aimed to highlight the mechanism of ATR-induced environmental nephrosis and the chemoprotective potential of lycopene (LYC) against the renal injury and nephrosis. Male mice were treated with LYC (5 mg/kg) and/or ATR (50 mg/kg or 200 mg/kg) by gavage administration for 21 days. Histopathological changes and biochemical function, cytochrome P450 enzymes system (CYP450s), nuclear xenobiotic receptors (NXRs) response and the transcription of CYP isoforms (CYPs) were detected. ATR exposure caused the changes of the histopathological and biochemical function, activated the NXR response and disturbed the CYP450s homeostasis. Supplementary LYC significantly prevented ATR-induced nephrotoxicity and alleviated the alternation of histopathological and biochemical function via modulating the CYP450s homeostasis and the NXR response. The results demonstrated AHR, CAR, PXR, PPAR (α, γ), CYP1, CYP2, CYP3 and CYP4 superfamily play a vital role in LYC-ATR interaction. Our findings provide new evidence that ATR exposure can cause the environmental nephrosis via inducing the kidney injury. Supplementary LYC showed significant chemoprotective potential against ATR-induced renal injury and environmental nephrosis via regulating the NXR response and the CYP450s homeostasis.

Relationship between blood toxin level and clinical features in patients with grayanotoxin poisoning - six clinical cases.

BACKGROUND: The purpose of this study was to investigate grayanotoxin (GTX) levels in the blood of patients with GTX intoxication and in the consumed Rhododendron liqueur, and to determine whether there was an association between blood GTX level and the patient's clinical status. METHODS: In September 2015, six patients were concurrently presented to the emergency department with various toxicity symptoms, which occurred after the consumption of Rhododendron liqueur at the same toxin concentration. Liquid chromatography-tandem mass spectrometry analysis was conducted on blood samples obtained from six cases of GTX intoxication treated in our emergency department. RESULTS: At the initial evaluation in the emergency department, the mean arterial pressure of the patients ranged from 36.7 to 76.7 mm Hg. The concentrations of GTX-I and GTX-III in Rhododendron liqueur were 1.436 and 16.907 ng/mL, respectively. The initial blood GTX-III and GTX-I levels ranged from 2.9 to 58.0 ng/mL and the lower limit of quantification (LLOQ) to 8.33 ng/mL, respectively. After 20 h, the mean arterial pressure ranged from 76.7 to 93.3 mm Hg, while the blood GTX-III and GTX-I levels ranged from the LLOQ to 17.8 and 2.52 ng/mL, respectively. DISCUSSION: We estimated that the minimum blood GTX-III and GTX-I levels that caused hypotension were between 17.83 and 27.3 ng/mL, and 2.52 and 4.55 ng/mL, respectively.

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

BACKGROUND: Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. OBJECTIVES: We present a case of intravenous poison hemlock injection encountered in the emergency department. CASE REPORT: We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. CONCLUSION: Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Severity scores and their associated factors among orally poisoned toddlers: a cross sectional single poison center study.

BACKGROUND: One of the most unfortunate events toddlers may encounter during their early years of curiosity and experimentation is substance poisoning. The aim of the study was to evaluate the poison severity score and its associated factors among toddlers with orally ingested substances at a pediatrics emergency department (ED), central Saudi Arabia. METHODS: A cross-sectional, poisoning report review between 2009&2011 was conducted. Exposures were patient characteristics (sex, age, body mass index, medical history) and incident characteristics (substance type, amount, form, witnessed or not, home remedy, arrival time to ED). Outcome was Poison Severity Score (PSS) that rates signs/symptoms of 11 body aspects on scale 0-4 (none, minor, moderate, severe, fatal). INCLUSION CRITERIA: age (1-3 years), previously healthy and oral exposure route. Bivariate analysis and multi-linear regression were conducted. Significance at p < 0.05. RESULTS: Eligible cases were 165/315(52 %). Males (58 %) and females (42 %) had normal BMI (70 %). Substances ingested were medications (60 %) and chemicals (40 %). Almost 85 % were witnessed incidents and 27 % received a home remedy (water, juices, dairy products, salt/sugar solutes, and/or manually induced vomiting). Delayed arrival (≥1 hour) was observed in 57 %. Composite mean PSS of total was (0.16 ± 0.21), and was highest at the gastrointestinal (GI) aspect (0.39 ± 0.63), metabolic balance (0.35 ± 0.60), and respiratory aspect (0.30 ± 0.61). Significantly associated factors with higher severity scores were: home remedies at the composite mean PSS (adj.p = 0.048), chemical poisoning at two aspects respiratory (adj.p = 0.047) and muscular (adj.p = 0.009) compared to medication poisoning. Unwitnessed incidents at the muscular aspect (adj.p = 0.026) compared to witnessed incidents; delayed arrival time to ED at three aspects GI (adj.p = 0.001), nervous system (adj.p = 0.014) and kidney (adj.p < 0.001). CONCLUSIONS: Parents are not recommended to provide any home remedy to their orally poisoned toddlers, but rather directly visit the ED. Physicians are expected to observe more severe clinical outcomes among toddlers with chemical poisoning, unwitnessed incidents, and delayed arrival times especially at the respiratory, GI, muscular, nervous and kidney aspects.

Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

Successful Rescue of a Patient with Acute Aconitine Poisoning Complicated by Polycystic Renal Hemorrhage.

INTRODUCTION: Aconitine is a highly toxic diterpenoid alkaloid, produced by plants of the Aconitum genus, that is still used in Chinese herbal medicines. Aconitine poisoning remains common in China and other parts of Asia. CASE REPORT: A 48-year-old man received a diagnosis of aconitine poisoning after ingesting herbal medicinal wine made with caowu, which is made from Aconitum kusnezoffii roots, and was admitted to our hospital' s emergency department. Electrocardiography and thoracoabdominal computed tomography showed cardiovascular toxicity from aconitine poisoning along with polycystic renal hemorrhaging. Because the arrhythmia was not controlled with lidocaine, blood purification with a reduced dosage of heparin was performed to treat the arrhythmia and to avoid increasing the bleeding of the polycystic renal hemorrhage. The patient recovered from aconitine poisoning and polycystic kidney hemorrhage. CONCLUSIONS: This case significantly advances our understanding of hemoperfusion with reduced heparin for the treatment of ventricular arrhythmia caused by aconitine poisoning.

Start me up! Recurrent ventricular tachydysrhythmias following intentional concentrated caffeine ingestion.

CONTEXT: Nearly pure caffeine is sold as a "dietary supplement," with instructions to ingest 1/64th to 1/16th of one teaspoon (50-200 mg). We report a patient with refractory cardiac dysrhythmias treated with defibrillation, beta-adrenergic blockade, and hemodialysis to highlight concentrated caffeine's dangers. CASE DETAILS: A 20-year-old woman presented with severe agitation, tremor, and vomiting approximately 1-2 h after suicidal ingestion of concentrated caffeine (powder and tablets). Within minutes, ventricular fibrillation commenced. Defibrillation, intubation, and amiodarone administration achieved return of spontaneous circulation (ROSC). Shortly thereafter, she developed pulseless ventricular tachycardia (VTach), with ROSC after defibrillation and lidocaine. She subsequently experienced 23 episodes of pulseless VTach, each responsive to defibrillation. Activated charcoal was administered via orogastric tube. An esmolol infusion was started. Hemodialysis was initiated once she was hemodynamically stable. She was extubated the following day, continued on oral metoprolol, and transferred to psychiatry on hospital day seven, achieving full neurological recovery. Serum caffeine concentrations performed approximately six and 18 h post-ingestion (pre/post-dialysis) were 240.8 mcg/mL and 150.7 mcg/mL. DISCUSSION: Severe caffeine toxicity can produce difficult to treat, life-threatening dysrhythmias. Concentrated caffeine, marketed for dietary supplementation, presents a substantial public health risk that demands action to limit consumer availability.

A Systematic Review of the Molecular Mechanisms of Uranium -Induced Reproductive Toxicity.

Uranium is the heaviest metal known as nuclear fuel, and employed in the production of glass tinting compounds, ceramic glazes, gyroscope wheels, chemical catalysts and X-ray tube targets. Inhalation and ingestion are two of the most usual ways of exposure. Uranium may be released into drinking water through the mining leading to contamination. Uranium is able to damage the DNA by generation of free radicals and acting as a catalyst in the Fenton reactions causing oxidative stress. In fact, reproductive system contains high amount of polyunsaturated fatty acids, and therefore it is highly vulnerable to reactive oxygen species (ROS) and sensitive to uranium toxicity. Toxic effects of uranium are generally reported through different mechanisms of action including inflammation, degeneration of testis, vacuolization of Leydig cells, spermatocytes necrosis, and oocyte dysmorphism. The present article provides a comprehensive review of the recent findings mostly about the molecular and biochemical toxicity of uranium on the reproductive system.

Methanol poisoning: predictors of visual outcomes.

OBJECTIVE: To determine whether laboratory markers of methanol ingestion and subsequent toxicity can serve as predictors of visual outcomes in patients. METHODS: Retrospective medical record review of 122 patients in a cluster outbreak of methanol poisoning. Data collected included history, complete ocular and systemic examination details, time to presentation, amount of alcohol ingested, and results of laboratory investigations, such as hemogram, glucose levels, hematocrit level, arterial pH, methanol levels, potassium and bicarbonate levels, and anion and osmolar gap determination, as well as hepatic and renal function tests. Therapy administered consisted of ethyl alcohol, sodium bicarbonate, and nutritional supplements, with hemodialysis in severe cases. Visual acuity (VA), pupillary reaction, and optic disc findings were assessed at presentation and 3 months after discharge. Patients were classified according to their visual disturbance: transient (group 1) or permanent (group 2). Appropriate statistical analysis was performed. Outcome measures included determining the association between biochemical markers of methanol poisoning and final VA. RESULTS: A total of 122 patients (1 female and 121 male) were admitted for treatment; of these, 10 died. Only 1 patient showed a 2-line drop in VA. pH was the strongest predictor of final VA and improvement in VA among all markers. The odds that a patient with an initial pH greater than 7.2 would have only transient visual disturbances were high (odds ratio, 31; 95% CI, 6-149). CONCLUSIONS: The degree of acidosis at presentation appears to determine final VA; early presentation and treatment did not seem to significantly alter the visual outcome, especially in severe poisoning.

Superwarfarin intoxication: two case reports and review of pathophysiology and patient management.

Superwarfarin vitamin K antagonists are found in rat poisons and are readily available. Pediatric exposures are common but are usually asymptomatic without significant coagulopathy. Superwarfarin intoxication must be considered in any adult who presents with an unexplained coagulopathy with extreme elevation of prothrombin time and partial thromboplastin time with associated depletion of vitamin K dependent factors. If superwarfarin toxicity is confirmed, intentional ingestion should be considered, as a large quantity of ingested rat poison is necessary to induce a coagulopathy. Patients with superwarfin induced coagulopathy require several months of high dose oral and parenteral vitamin K supplementation. We describe two patients with superwarfarin toxicity treated at Louisiana State University Health in Shreveport and review pathophysiology and patient management.

Toxicology in the ICU: Part 1: general overview and approach to treatment.

Poisonings, adverse drug effects, and envenomations continue to be commonly encountered. Patients often present critically ill and warrant ICU admission. Many other patients who are initially stable have the potential for rapid deterioration and require continuous cardiopulmonary and neurologic monitoring. Given the potential for rapid deterioration, and because patients need continuous monitoring, ICU admission is frequently required. This article is the first of a three-part series to be published in CHEST; it discusses general management, laboratory tests, enhanced elimination, and emerging therapies. The second article will address the management of specific overdoses; the last will cover plants, mushrooms, envenomations, and heavy metals.

Aconitine intoxication mimicking acute myocardial infarction.

INTRODUCTION: Cardiotoxicity in acute aconitine intoxication is well known; however, elevation of troponin I level and abnormal scintigraphy findings had not previously been reported. CASE REPORT: A 60-year-old man developed chest tightness, syncope and convulsion after ingesting processed Aconitum carmichaeli (Chuanwu) extract for treatment of headache. Electrocardiogram showed first degree atrioventricular (AV) block. Troponin I level was elevated at 14.8 ng/mL 13 hours post-ingestion. Creatine kinase was also increased to 414 U/L. However, echocardiography did not show any abnormal cardiac wall motion. Tc-99m-PYP scintigraphy revealed diffusely increased uptake in the myocardium, suggesting the presence of myocardial necrosis or myocarditis. DISCUSSION: Aconitine poisoning can mimic acute myocardial infarction with chest tightness and elevated cardiac enzymes. Increased cardiac markers and myocardial insult seen in this patient were likely to be related to the toxicity of aconitine. Care should be taken in making the diagnosis in such instances. Management is primarily supportive.

Removal of thallium by deferasirox in rats as biological model.

The present research aimed to characterize the potential efficiency of deferasirox in removing thallium after its administration for 30 days following two dose levels of 20 and 160 µm of thallium (III) chloride to male Wistar rats every day. After thallium administration some abnormal clinical signs such as red staining around the eyes, greenish mottling on the liver, weakness, loss of hair and weight, were observed in animals. Deferasirox was given orally to different groups of rats for a period of one week immediately after thallium administration. After chelation therapy, animals were killed by exsanguination from the abdominal aorta, and then thallium and iron concentrations in various tissues were determined by standard addition method. The chelation therapy results showed that deferasirox was able to remove thallium ions from the body and clinical symptoms were also reduced.

Calcium channel blocker toxicity.

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Pediatric toxicology.

Pediatric patients present unique concerns in the field of medical toxicology. First, there are medicines that are potentially dangerous to small children, even when they are exposed to very small amounts. Clinicians should be wary of these drugs even when young patients present with accidental ingestions of apparently insignificant amounts. Next, over-the-counter laxatives and syrup of ipecac, although not commonly considered abused substances, may be misused in both the setting of Munchausen's syndrome by proxy and in adolescents who have eating disorders. Their use should be considered in any gastrointestinal illness of uncertain origin. Finally, as the use of syrup of ipecac at home now has been discouraged by many, some have explored using activated charcoal at home as a new method of prehospital gastrointestinal decontamination. The literature examining activated charcoal and its use in this capacity is discussed.

Consensus meeting on "Relevance of parenteral vitamin C in acute endothelial dependent pathophysiological conditions (EDPC)".

The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in the treatment of endothelial dysfunction. Scientists, who had published and reviewed scientific and regulatory papers on that topic were invited, among them basic researchers, toxicologists, clinicians and nutritionists. The participants were presented with eleven questions, which were discussed and answered at the workshop, with the aim of summarising the current state of knowledge. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. The therapeutic relevance of administration of the physiological antioxidant vitamin C in high parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC) was discussed. Endothelial dysfunction is defined as including disturbed endothelial dependant relaxation of resistance vessels, breakdown of the microvascular endothelial barrier and/or loss of anti-adhesive function. It occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma, and ischemic-reperfusion tissue injury and is induced by oxidative stress. Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and organ transplantation. Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids. There is experimental evidence that parenteral high-dose vitamin C restores endothelial function in sepsis. In vitro, supraphysiological concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and endothelial function. Only parenterally, can enough vitamin C be administered to combat oxidative stress. There is no evidence that parenteral vitamin C exerts prooxidant effects in humans. Theoretical concerns in relation to competitive interactions between vitamin C and glucose cellular uptake are probably only relevant for oxidised vitamin C (dehydroascorbate).

Iron: not a benign therapeutic drug.

PURPOSE OF REVIEW: This article reviews the pathophysiology and clinical presentation of iron poisoning. Recently proposed guidelines for triage of children with iron ingestion will be discussed as well as diagnostic and treatment modalities. Finally, the potential impact of unit-dose packaging as a primary preventative measure will be discussed. RECENT FINDINGS: Carbonyl iron has a greater safety margin than the iron salts. There have been no published reports of serious or fatal poisoning from the ingestion of carbonyl iron products. Evidence-based consensus guidelines have determined that the threshold for referral to a healthcare facility is 40 mg/kg of elemental iron in the form of adult iron formulations. Unit-dose packaging of iron preparations appeared to decrease the number of exposures to iron and deaths in the United States during the period they were instituted. SUMMARY: Iron poisoning remains primarily a clinical diagnosis, although certain laboratory and radiological testing may provide helpful evidence to guide evaluation and management. Primary prevention is the best modality for decreasing morbidity and mortality for all poisonings including iron.

Visual field defects in epidemic dropsy.

UNLABELLED: Epidemic dropsy is a multi-system disease involving the cardiovascular, hepatic, renal, ocular and other systems. It is a toxic disease caused by the unintentional ingestion of Argemone mexicana (prickly yellow poppy) seeds as an adulterant of wheat flour or more commonly of cooking oil such as mustard oil. PURPOSE: To investigate the occurrence of visual field defects in patients suffering from epidemic dropsy glaucoma. METHODS: Visual field analysis was performed to ascertain the field defects, in patients suffering from epidemic dropsy. Group I consisted of 35 patients (69 eyes) whose intraocular pressure (IOP) was > or = 22 mmHg. Ten dropsy patients (20 eyes) with normal IOP (<22 mm Hg) formed Group II. Ten healthy unexposed volunteers (20 eyes) constituted Group III. All the patients were tested using the Armaly full field glaucoma screening test on the Humphrey field analyzer. RESULTS: Forty seven of the 69 eyes (68%) suffering from epidemic dropsy glaucoma, and 18 out of 20 (90%) eyes in dropsy patients with normal IOP, showed field defects. In the control group, 15% eyes had only nasal field defects. The difference between Group I and II was not significant (p = 0.054), though the field defects were significantly more frequent in dropsy patients as compared to the controls (p < 0.01 in either case). The results suggest that visual field defects in epidemic dropsy occur independently of the rise in intraocular pressure. Field defects were detected more frequently in patients who underwent visual field analysis early in the course of disease, as compared to those who underwent screening later on in the disease course. CONCLUSIONS: In epidemic dropsy, acute visual field defects occur independent of rise of intraocular pressure and more frequently in the early stage of the disease.

Acute Erycibe henryi Prain ("Ting Kung Teng") poisoning.

Erycibe henryi Prain ("Ting Kung Teng"), a species of Convolvulaceae, has been used in Chinese medicine to relieve pain involving the musculoskeletal system, such as arthritis, sciatica, and traumatic tissue swelling. E. henryi can be mistaken for another herbal plant, Tripterygium wilfordii Hook F, used to treat gouty arthritis. We report here three cases of E. henryi poisoning. All three cases presented with vomiting, diarrhea, salivation, diaphoresis, lacrimation, and rhinorrhea; two patients also had miosis, hypothermia, bradycardia, hypotension, and ventricular tachyarrhythmias. Laboratory abnormalities included leucocytosis, hyperglycemia, hyperamylasemia, hypocalcemia, and transiently elevated liver enzymes, creatinine and creatinine phosphokinase. The active constituents of E. henryi include several tropane alkaloids, which exhibit cholinergic activities. Gastrointestinal disturbances and ventricular tachyarrhythmias may occur with ingestion of either E. henryi or T. wilfordii, but the cholinergic symptoms can help to differentiate them.