Successful Management of Severe Bromethalin Toxicosis in a Dog.

ABSTRACT The use of bromethalin rodenticides has risen since 2011, and in some states, it is the most common rodenticide ingestion reported to poison control. Although intravenous lipid emulsion (ILE) has been previously reported to lower serum desmethylbromethalin levels in an asymptomatic dog, and repeated mannitol has been investigated in a laboratory setting, there are no published reports of successful treatment of symptomatic bromethalin toxicosis in dogs. A 9 yr old castrated male Norwich terrier was evaluated for obtunded mentation, seizures, cranial nerve deficits, and tetraparesis secondary to bromethalin toxicosis. The patient was treated with ILE, mannitol, and ginkgo biloba and returned to normal neurological function. Bromethalin exposure was confirmed by serum desmethylbromethalin levels. Previous literature indicates that the prognosis for patients who suffer from symptomatic bromethalin toxicosis is poor to grave, and the return to normal neurological function after severe toxicosis has not been reported. ILE, mannitol, and ginkgo biloba are readily available and relatively inexpensive, and in combination may be of benefit in symptomatic bromethalin intoxication.

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats.

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP-induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.

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.

Anti-endotoxin and anti-inflammatory effects of Chinese herbal medicinal alkaloid ingredients in vivo.

The aim of the research was to investigate the anti-endotoxin and anti-inflammatory effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine, and evodiamine alkaloids commonly found in Chinese herbal medicines. In an endotoxin (LPS) control group, each mouse was challenged with 1 mg LPS/kg by intraperitoneal (IP) injection. In high-, middle- and low-dose alkaloid groups, mice were initially challenged with 1 mg LPS/kg by IP injection and, 3 h later, dosed intramuscularly (IM) with one of the six alkaloids at one of three levels (1, 5, or 10 mg/kg body weight). In the drug control group, mice were dosed IM with 10 mg/kg body weight of a given alkaloid; mice in a naïve control group were administered the same volume of normal saline. The results revealed the six alkaloids could reduce the incidence/severity of LPS- induced toxicities, e.g., body temperature elevation, weight loss, systemic inflammation, multiple organ dysfunction. Taken together, the data suggested to us that these alkaloids might effectively regulate inflammatory responses and have a potential to be used in anti-endotoxin therapies.

A novel strain of Cellulosimicrobium funkei can biologically detoxify aflatoxin B1 in ducklings.

Two experiments were conducted to screen microorganisms with aflatoxin B1 (AFB1 ) removal potential from soils and to evaluate their ability in reducing the toxic effects of AFB1 in ducklings. In experiment 1, we screened 11 isolates that showed the AFB1 biodegradation ability, and the one exhibited the highest AFB1 removal ability (97%) was characterized and identified as Cellulosimicrobium funkei (C. funkei). In experiment 2, 80 day-old Cherry Valley ducklings were divided into four groups with four replicates of five birds each and were used in a 2 by 2 factorial trial design, in which the main factors included administration of AFB1 versus solvent and C. funkei versus solvent for 2 weeks. The AFB1 treatment significantly decreased the body weight gain, feed intake and impaired feed conversion ratio. AFB1 also decreased serum albumin and total protein concentration, while it increased activities of alanine aminotransferase and aspartate aminotransferase and liver damage in the ducklings. Supplementation of C. funkei alleviated the adverse effects of AFB1 on growth performance, and provided protective effects on the serum biochemical indicators, and decreased hepatic injury in the ducklings. Conclusively, our results suggest that the novel isolated C. funkei strain could be used to mitigate the negative effects of aflatoxicosis in ducklings.

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.

Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose.

Manganese is a ubiquitous, essential trace element and a common ingredient of joint supplement tablets. Little information is known about the inherent toxic potential if ingested at higher doses. A 5-year-old female spayed Pug dog presented for evaluation of vomiting and ataxia after accidental ingestion of approximately 100 joint supplement tablets. The dog developed acute hepatic failure and was euthanized 6 days after presentation due to progression of the disease. Necropsy showed severe acute hepatic necrosis. Liver and kidney samples were submitted for toxicology analysis, results of which showed severely elevated manganese concentrations in the liver and kidneys.

Teratogenic effects and monetary cost of selenium poisoning of fish in Lake Sutton, North Carolina.

Selenium pollution from coal ash wastewater was investigated in Lake Sutton, NC. This lake has been continuously used as a cooling pond for a coal-fired power plant since 1972. Historic and recent levels of contamination in fish tissues (14-105µg Se/g dry weight in liver, 24-127 in eggs, 4-23 in muscle, 7-38 in whole-body) exceeded toxic thresholds and teratogenic effects were observed in fish collected in 2013. A high proportion (28.9 percent) of juvenile Lepomis spp. exhibited spinal and craniofacial malformations that were consistent with selenium poisoning. Teratogenic Deformity Index values indicated population-level impacts on the fishery. The partially monetized cost of resultant fishery losses was calculated at over $US 8.6 million annually, and over $US 217 million for the entire period of damage, which dates back to 1987 when chemical and biological monitoring began.

Surviving acute cyanide poisoning: a longitudinal neuropsychological investigation with interval MRI.

We report the case of a 22-year-old woman who presented with self-poisoning by cyanide ingestion. We have elected to pay particular attention to describing the neuropsychological sequelae of cyanide poisoning, and the evolution of these deficits over a 6-month period. Prominent deficits in episodic memory were noted from an early stage, which were consistent with the findings noted on structural neuroimaging. These deficits remained persistent, although improving in severity over the follow-up period. No focal neurological deficits or abnormal involuntary movements emerged, and the patient's overall functional status remained satisfactory. The patient's psychiatric presentation and background history are briefly discussed.

Pathogenesis and preventive treatment for animal disease due to locoweed poisoning.

Locoweeds are perennial herbaceous plants included in Astragalus spp. and Oxytropis spp. that contain the toxic indolizidine alkaloid swainsonine. The livestock that consume locoweed feeding can suffer from a type of toxicity called "locoism." There are aliphatic nitro compounds, selenium, selenium compounds and alkaloids in locoweed. The toxic component in locoweeds has been identified as swainsonine, an indolizidine alkaloid. Swainsonine inhibits lysosomal α-mannosidase and mannosidase II, resulting in altered oligosaccharide degradation and incomplete glycoprotein processing. As a result, livestock that consume locoweeds exhibit several symptoms, including dispirited behavior, staggering gait, chromatopsia, trembling, ataxia, and cellular vacuolar degeneration of most tissues by pathological observation. Locoism results in significant annual economic losses. Recently, locoweed populations have increased domestically in China and abroad, resulting in an increase in the incidence of poisoning. Therefore, in this paper, we review the current research on locoweed, including on species variation, pathogenesis, damage and poisoning prevention measures.

Phytochemical, toxicological and antimicrobial evaluation of Lawsonia inermis extracts against clinical isolates of pathogenic bacteria.

BACKGROUND: The emerging resistance of pathogen against the currently available antimicrobial agents demands the search of new antimicrobial agents. The use of medicinal plants as natural substitute is the paramount area of research to overwhelm the drug resistance of infectious agents. Scientists have not made enough effort on the evaluation of safety of medicinal plant yet. METHODS: In the present study antimicrobial activity of Lawsonia inermis is investigated against clinical isolates of seven bacteria including four Gram negative (Escherichia coli, Salmonella typhi, Klebsiella spp., Shigella sonnei) and three Gram positive (Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis) using disc diffusion method. Four types of Lawsonia inermis extracts were prepared using methanol, chloroform, acetone and water as extraction solvents, while DMSO (Dimethyl sulfoxide) and water as dissolution solvents. The rate and extent of bacterial killing was estimated by time-kill kinetic assay at 1× MIC of each bacterial isolate. The overall safety of Lawsonia inermis extracts was assessed in mice. RESULTS: Lawsonia inermis displayed noteworthy antimicrobial activity against both gram positive and gram negative bacterial strains used in the study. The minimum value of MIC for different bacterial strains ranged from 2.31 mg/ml to 9.27 mg/ml. At 1x MIC of each bacterial isolate, 3log10 decrease in CFU was recorded after 6 hours of drug exposure and no growth was observed in almost all tested bacteria after 24 hours of exposure. No sign of toxidrome were observed during in vivo toxicity evaluation in mice at 300 mg/kg concentration. CONCLUSION: In conclusion, the present study provides the scientific rational for medicinal use of Lawsonia inermis. The use of Lawsonia inermis extracts is of great significance as substitute antimicrobial agent in therapeutics.

Copper toxicosis in New Zealand White rabbits (Oryctolagus cuniculus).

Six 12- to 14-month-old New Zealand White rabbits were diagnosed with copper toxicosis. These rabbits were part of a group of 110 purchased and shipped overnight for research purposes. On arrival, the group experienced an abrupt diet change. Eight died over 3 weeks and 6 were submitted for postmortem examination. Microscopic findings included severe centrilobular to midzonal hepatocellular necrosis with rhodanine stain-positive copper granules in the remaining hepatocytes. Mild periportal fibrosis and biliary hyperplasia, hemoglobinuric nephrosis, and splenic erythrophagocytosis were also observed. Hepatic copper concentrations were elevated, ranging from 319 to 997 ppm. Clinical disease was not previously observed in younger rabbits gradually transitioned from the supplier's copper-supplemented diet. Copper toxicosis likely occurred in these rabbits from a combination of (1) increased duration of copper supplementation leading to increased hepatocellular stores and (2) stress leading to anorexia and release of hepatocellular copper stores similar to chronic copper toxicosis as described in sheep.

Contents of various elements in the organs of seabirds killed by an oil spill around Tsushima Island, Japan.

Twenty nine oil-soaked birds were collected from around the Coast of Tsushima Island. The contents of eight elements in the livers and kidneys of the birds were investigated. Statistically higher concentrations of vanadium and thallium in the liver and of titanium in the kidney were found in the birds that were found dead compared with those that died after rescued. A significant correlation (r=0.695, P<0.01) was observed only for the molybdenum content between the kidneys and livers from the birds found dead. Although the controls of the eight elements of birds investigated in the present study remain unexplained, some of lower concentration in rescued birds can be blamed on a decrease in food intake of birds. The relation between oil contamination and concentration of elements need to be further explored.

Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus.

The basal ganglia and thalamus are paired deep gray matter structures that may be involved by a wide variety of disease entities. The basal ganglia are highly metabolically active and are symmetrically affected in toxic poisoning, metabolic abnormalities, and neurodegeneration with brain iron accumulation. Both the basal ganglia and thalamus may be affected by other systemic or metabolic disease, degenerative disease, and vascular conditions. Focal flavivirus infections, toxoplasmosis, and primary central nervous system lymphoma may also involve both deep gray matter structures. The thalamus is more typically affected alone by focal conditions than by systemic disease. Radiologists may detect bilateral abnormalities of the basal ganglia and thalamus in different acute and chronic clinical situations, and although magnetic resonance (MR) imaging is the modality of choice for evaluation, the correct diagnosis can be made only by taking all relevant clinical and laboratory information into account. The neuroimaging diagnosis is influenced not only by detection of specific MR imaging features such as restricted diffusion and the presence of hemorrhage, but also by detection of abnormalities involving other parts of the brain, especially the cerebral cortex, brainstem, and white matter. Judicious use of confirmatory neuroimaging investigations, especially diffusion-weighted imaging, MR angiography, MR venography, and MR spectroscopy during the same examination, may help improve characterization of these abnormalities and help narrow the differential diagnosis.

Modulating effect of aqueous extract of Telfairia occidentalis on induced cyanide toxicity in rats.

The effect of lyophilised aqueous extract of Telfairia occidentalis (TO) on induced cyanide toxicity in rats was investigated. Twenty 3-week old male wistar albino rats were randomly distributed into one control and three treatment groups of five rats each: control group (group1), group treated with 3mg/kg body wt of cyanide only (group2), group treated with 3mg/kg body wt. each of cyanide and extract (group3), and a group treated with 3mg/kg Body wt of extract only (group4) were used for the investigation. Cyanide toxicity reduced both food and water intake (p<0.05), while the food intake was improved in group3, this effect of the extract on food was not observed on water intake. Cyanide reduced average body weight of rats significantly (p<0.05). The reduction effect of cyanide on body weight was countered by Telfairia occidentalis extract. The extract did not have an observable effect on rats' body weight. Ocular lesion was observed in 67% of rats in group2 . This ocular effect of cyanide was mitigated significantly by Telfairia occidentalis as only 17% of the rats in group3 had ocular lesion. Cyanide toxicity produced nasal discharge in 39% of the rat population in group2 while there was a partial but considerable reduction (21%) in the severity of nasal discharge in group 3. There was no significant difference (p>0.05) in the organ/body wt.ratio between the treatments and the control groups for all the organs examined in the study. Biochemical analysis of liver enzymes showed that cyanide (group2) damaged the liver as there was significantly elevated presence (p<0.05) of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALP) above those of the control group. The damaging effect of cyanide on the liver was ameliorated by Telfairia occidentalis considerably.Histopathological effect of cyanide toxicity on the organs examined included multifocal degeneration and necrosis of the liver, mild kidney congestion and congestion of the brain. These effects were moderated mildly by Telfairia occidentalis. Group 4, treated with the vegetable alone had none of the observed histopathology in the organs examined. We concluded that lyophilised aqueous extracts of Telfairia occidentalis showed good potential as a safe antidote for cyanide poisoning when administered concomitantly or very shortly after ingestion of sub-lethal dose of cyanide. However, further bioassay guided fractionation and analytical studies are needed to identify the actual chemical compound or molecule in the vegetable responsible for or associated with the observed effects.

A rare case of brucine poisoning complicated by rhabdomyolysis and acute renal failure.

Brucine is the predominant alkaloid present in the bark of the tree Strychnos nux vomica and is a weaker alkaloid when compared to strychnine. However, its toxicological property is akin to strychnine. We report a rare case of brucine poisoning complicated by acute renal failure and rhabdomyolysis. A 24-year-old male presented with a history of consumption of a decoction made from the bark of the Strychnos nux vomica tree. Soon after, he developed widespread muscle spasms and convulsions, which were promptly treated. On the fifth day of admission, he developed features of rhabdomyolysis and acute renal failure. Investigations revealed elevated creatine phosphokinase levels and elevated blood urea and serum creatinine. The patient was managed with hemodialysis and recovered gradually. There are many reports of strychnine poisoning producing rhabdomyolysis and renal failure. In this case report, attention is drawn to the fact that brucine, although a weaker alkaloid, can also produce life threatening complications like rhabdomyolysis and acute renal failure.

Aspectos clínico-patológicos e laboratoriais do envenenamento crotálico experimental em bovinos / Clinical and pathological aspects of experimental Crotalus poisoning in cattle

Reproduziu-se experimentalmente o envenenamento crotálico, através da inoculação, por via subcutânea, do veneno de Crotalus durissus terrificus (cascavel sul-americana) em dez bovinos mestiços. Dois animais foram utilizados como controle. O bovino que recebeu dose de 0,03mg/kg de peso corporal, morreu 7h40min após a inoculação. A dose de 0,015mg/kg causou a morte em quatro de sete bovinos inoculados, enquanto os dois animais que receberam 0,0075mg/kg adoeceram discretamente e se recuperaram. Os sintomas tiveram início entre 1h30min e 13h45min após a inoculação. A evolução oscilou entre 5h25min e 45h para os animais que morreram e entre 33h15min e 17 dias entre os animais que se recuperaram. Os principais sinais nervosos observados foram diminuição da resposta aos estímulos externos, reflexos hipotônicos, arrastar dos cascos no solo, aparente apatia, paralisia do globo ocular e da língua, decúbito esternal e lateral. Verificaram-se também adipsia e, por vezes, petéquias nas mucosas vaginal e conjuntival. Houve discreto a moderado aumento do tempo de sangramento e moderado aumento do tempo de tromboplastina parcial ativada. Houve moderada leucocitose com neutrofilia, linfopenia relativa, eosinopenia, monocitose e discreto aumento do número de bastões. Foi evidenciado significativo aumento dos níveis séricos de creatinaquinase, contudo, não foram observadas alterações significativas através da urinálise. À necropsia constataram-se edema quase imperceptível no local da inoculação, discretas petéquias e sufusões no epicárdio, omento, vesícula biliar e mucosa da bexiga em alguns dos animais envenenados experimentalmente. Os exames histopatológicos revelaram necrose (hialinização) de grupos de miócitos ou em miócitos isolados em dez diferentes músculos esqueléticos examinados, próximos ou distantes do local de inoculação em todos os animais necropsiados. Concluí-se que o envenenamento por Crotalus Sul-americanas em bovinos não cursa com mioglobinúria...

Crotalus poisoning was experimentally reproduced by subcutaneous inoculation of Crotalus durissus terrificus (South American rattlesnake) venom into 10 clinically healthy mixed bred 12 to 36-month-old cattle, weighing 125 to 449 kg. Two animals were used as controls. The animal that received a dose of 0.03mg/kg body weight died 7h40min after inoculation. A 0.015mg/kg dose provoked death in 4 out of 7 young oxen. Two animals given 0.0075mg/kg became slightly sick and recovered. Onset of symptoms occurred from 1h30min to 13h45min after inoculation. The clinical course varied from 5h25min to 45h for animals that died, and from 33h15min to 17 days for animals that recovered. The main nervous signs observed were diminished response to external stimuli, hypotonic reflexes, dragging of the hooves, apathy, difficulties in moving around obstacles, ocular globe paralysis, lateral and sternal decubitus, and tongue paralysis. Adipsia and sometimes petechiae in the conjunctival and vaginal mucosa were observed. A slight to moderate increase in bleeding time was noted in 6 animals, and a moderate increase in partial thromboplastin time was found in 7 others. Moderate leukocytosis with neutrophilia, relative lymphopenia, eosinopenia, and monocytosis was found. There was a significant increase in creatine kinase serum levels of a ten-fold order. No significant alterations were revealed by urinalysis. Necropsy revealed minimal edema at the inoculation site, few petechiae and equimoses in the epicardium, omentum, biliary vesicle and bladder mucosa of some animals. Histopathological examination revealed necrosis (hyalinization) of groups or isolated myocytes in different muscles examined, both near and far from the inoculation site, in all animals. The diagnosis of Crotalus poisoning and its differentiation from diseases causing paralysis and muscular necrosis in cattle in Brazil are discussed.

Effect of tiron and its combination with nutritional supplements against vanadium intoxication in female albino rats.

In the present study an attempt has been made to evaluate the effect of Tiron along with Zinc, Selenium and Vitamin E against vanadium intoxication in female albino rats. Toxicant caused significant increase in the activities of serum transaminases, serum alkaline phosphatase and lactate dehydrogenase. Significant decrease was observed in blood sugar, serum albumin and triglyceride levels whereas serum proteins, cholesterol and urea levels increased significantly during toxicity (p