bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotoxic Effects Induced by Intracerebral and Systemic Injection of Paraquat in Rats
Authors: Corasaniti M.T. , Bagetta G. , Rodinò P. , Gratteri S. , Nisticò G. 
Published: December 2008

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats.2 Intrahippocampal microinfusion of paraquat (0.1 μmol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of paraquat (0.2-0.4 μmol) into the locus coeruleus, substantia nigra or into the raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are present, respectively, elicited potent excitotoxic effects (n=6 rats per dose and area). A lower dose (0.01 μmol) of the herbicide or injection of the vehicle (1.0 μl) did not produce any behavioural, ECoG or neurodegenerative effect.3 After systemic administration, paraquat (20 mg kg-1s.c.) evoked limbic motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats neuronal cell death was observed in the pyriform cortex, but not in other brain regions. A dose of 5 mg kg-1was ineffective.4 Among the regions of the brain studied, high concentrations of paraquat were detected in the pyriform cortex 24 h after systemic administration (5.0 and 20 mg kg-1s.c.) lower levels being observed in the caudate nucleus.5 In conclusion, paraquat, given systemically or intracerebrally in rats produces neurodegenerative effects.
Behavioural Toxicity of Anticholinesterases in Humans and Animals - A Review
Authors: D'Mello G.D. 
Published: December 2008

1 Available information describing the behavioural changes induced by anticholinesterases in humans and animals is reviewed.2 Very little confidence can be placed in existing descriptions of the behavioural effects of anticholinesterases in humans.3 Although data from animal experimental studies is reliable, the information obtained is relatively superficial.4 It is concluded therefore, although much information is available, surprisingly little is known of the behavioural changes induced by anticholinesterases.
A Retrospective Study of Poisoning due to Snake Venom in Zimbabwe
Authors: Kasilo O.M.J. , Nhachi C.F.B. 
Published: December 2008

1 Hospital records at the six major referral hospitals in urban Zimbabwe were reviewed for the years 1980-1989 in order to determine the types of snake, incidence, morbidity and mortality associated with snake venom poisoning. 2 A total of 1087 cases of animal toxin poisoning were retrieved retrospectively, 91.5% (995) of which were due to snake venom poisoning. Of the 995 cases, 50.9% (506) were females and 49.1% (489) males. The majority of patients were aged from 21 to 30 years (22%), followed by the 6-15 (16%) and the 16-20 year age groups (11 %), respectively. 3 The mean period of hospitalization of a snake venom-poisoned patient was found to be 2 d (the range was 1 d - 9 weeks). The mean total cost of keeping (excluding treatment) a poisoned patient during that period was calculated at Zimbabwean dollars (Zw$) 450.00 (US$ 225.00) per day. The total number of hospitalization days was 344 and the cost of keeping the patients in hospital was therefore Zw$ 154800 (i.e. US$ 77400). 4 The first-line treatment most used was a combination of antibiotics (44.6%), alone or with an antivenom tropical snake polyvalent (ATT) (21.2%), and analgesics (19.9%). 5 Mortality was recorded at 1.8% (18 patients) and the few records of the types of snakes associated with envenomation in order of frequency were the cobra, adders (puff and night), mamba and boomslang. The prevention and prompt treatment of snake envenomation is of priority in the reduction of incidence of poisoning.
Effect of Methanol or Modifications of the Hepatic Glutathione Concentration on the Metabolism of Dichloromethane to Carbon Monoxide in Rats
Authors: Pankow D. , Jagielki S. 
Published: December 2008

1 The metabolism of dichloromethane (DCM) to carbon monoxide as measured by the carboxyhaemoglobin (COHb) level in the blood is stimulated by pretreatment with methanol (MET). After simultaneous administration of both DCM, 6.2 mmol kg-1p.o., and MET, > 148 mmol kg-1p.o., the COHb formation is inhibited.2 MET ingestion results in a transient decrease of the glutathione (GSH) content of the liver. In rats treated with GSH-depleting chemicals such as diethylmaleate (DEM), phorone (PHO), or buthionine sulphoximine (BSO) there were no enhancements of the carboxyhaemoglobinaemia caused by DCM. The COHb formation was not influenced by an increase of the hepatic GSH concentration due to repeated administration of butylated hydroxyanisole (BHA).3 It is concluded that cytochrome P450 IIEl (CYP 2E1) is responsible for the metabolic interaction of both DCM and MET, and MET may be an inducer of CYP 2E 1. The two pathways of DCM, the oxidative via CYP 2E l and the metabolism via GSH/GSH-S-transferase seem to be independent.
Analysis of Polychlorinated Dioxins and Furans in Samples of the Toxic Oil Syndrome
Authors: Guitart Raimon , Nørgaard Lars , Mariani Giulio , Posada Manuel , Abaitúa Ignacio , Gelpi Emilio , Fanelli Roberto 
Published: December 2008

1 Polychlorinated dioxins (PCDDs) and furans (PCDFs) are known to produce a wide range of toxic effects. 2 PCDDs and PCDFs are typical contaminants of chlorinated phenols, and pentachlorophenol and related compounds have been shown to be widely distributed among selected oil samples taken from the 1981 Spanish toxic oil epidemic. 3 Six control and eight case oil samples were analysed using GC/MS for PCDDs and PCDFs. Only small concentrations, normally below 1 ng g-1, of the higher chlorinated PCDDs and PCDFs were detected. There were no statistical differences between the case and control oils. 4 These levels seem to be too low to elicit toxic effects, although they could be enough to potentiate the toxicity of other xenobiotics present in the oils. However, it is uncertain whether the levels of these compounds measured in 1990 reflect the levels present when the oils were consumed in 1981, or whether or not the levels measured in crude oils are representative of fried oils.
Desferrioxamine Treatment Reduces Histological Evidence of Lung Damage in Rats after Acute Nitrogen Dioxide (NO2) intoxication
Authors: Meulenbelt J. , Dormans J.A.M.A. , van Bree L. , Rombout P.J.A. , Sangster B. 
Published: December 2008

1 In previous studies a rat inhalation model was developed to investigate the efficacy of treatment in acute NO2 intoxication. 2 Desferrioxamine was administered intravenously to study its effect on histological alterations in lung tissue in rats after acute NO2 exposure. 3 Twenty four hours after exposure to 175 ppm NO2 for 10 minutes the lung injury observed by light microscopy in the desferrioxamine treated rats was less pronounced than in the saline treated rats. 4 Desferrioxamine appeared to provide more protection with a dose of 100 mg kg-1 24 h-1 than with 200 mg kg-1 24 h-1.
Human Pentachlorophenol Poisoning
Authors: Jorens Philippe G. , Schepens Paul J.C. 
Published: December 2008

Pentachlorophenol (PCP) was, and still is, one of the most frequently used fungicides and pesticides, Its toxicity is due to interference with oxidative phosphorylation. Acute and chronic poisoning may occur by dermal absorption, inhalation or ingestion. Chronic poisoning occurs mainly in sawmill workers or people living in log homes treated with PCPcontaining wood protecting formulations. Quantitative determination of PCP in urine and serum is useful to detect occupational or subclinical exposure. The clinical features of acute and chronic PCP poisoning can be classified systematically into effects on the skin, metabolism (fever), the haematopoietic tissue, the respiratory system, the central and peripheral nervous system, the kidney and the gastrointestinal tract. Although PCP is not classified as a human carcinogen, some epidemiological observations suggest that exposure to chlorophenols in general and PCP solutions in particular may result in an increased risk for certain malignant disorders such as nasal carcinoma and soft tissue sarcoma. There is concern that contamination of PCP-solutions with products such as chlorodibenzo-p-dioxins is the real cause of this suspected carcinogenicity. No specific antidote exists for the treatment of (acute) PCP poisoning. The basis of the treatment of acute poisoning is intensive supportive care with prevention of dangerous rise in temperature. Use of PCP-based products as indoor wood preservatives poses an unacceptable risk to human health.
A Physiologically Based Mathematical Model of Dermal Absorption in Man
Authors: Auton T.R. , Westhead D.R. , Woollen B.H. , Scott R.C. , Wilks M.F. 
Published: December 2008

A sound understanding of the mechanisms determining percutaneous absorption is necessary for toxicological risk assessment of chemicals contacting the skin. As part of a programme investigating these mechanisms we have developed a physiologically based mathematical model. The structure of the model parallels the multi-layer structure of the skin, with separate surface, stratum corneum and viable tissue layers. It simulates the effects of partitioning and diffusive transport between the sub-layers, and metabolism in the viable epidermis. In addition the model describes removal processes on the surface of the skin, including the effects of washing and desquamation, and rubbing off onto clothing. This model is applied to data on the penetration of the herbicide fluazifop-butyl through human skin in vivo and in vitro. Part of this dataset is used to estimate unknown model parameter values and the remainder is used to provide a partial validation of the model. Only a small fraction of the applied dose was absorbed through the skin; most of it was removed by washing or onto clothing. The model provides a quantitative description of these loss processes on the skin surface.
Osmolal and Anion Gaps in Patients Admitted to an Emergency Medical Department
Authors: Aabakken Lars , Johansen Kjerstin S. , Rydningen Else-Berit , Bredesen Jan E. , Øvrebø Steinar , Jacobsen Dag 
Published: December 2008

1 Osmolal and anion gaps are helpful in the diagnosis and evaluation of intoxications with methanol and ethylene glycol. Reported reference values for osmolal gap and anion gap are -1 (± 6) mosm kg-1 H2O and 16 (± 2) mmol I -1, respectively. However, we have repeatedly found unexplained increased gaps in patients admitted to our department, and the relevance of the established reference values has been questioned. 2 Osmolal and anion gaps were determined in an unselected population of patients consecutively admitted to an emergency medical department. In the case of unexplained gaps, the blood samples were analysed with respect to the presence of alcohols and organic acids. 3 We included all accessible patients admitted during 14 days. Appropriate blood samples were obtained in 177 patients (88 male, 89 female), with a mean age of 65 years (range 17-94). 4 The mean and (standard deviation) for osmolal and anion gaps in our material were 5.2 mosm kg-1 H2O (7.0) and 12.9 mmol/l (4.2). Neither methanol nor ethylene-glycol was detected in serum from any patients. Small amounts of ethanol were found in 5 patients, and high lactate levels explained in part the most extensively increased anion gaps. However, the calculated analytical standard deviation accounted entirely for the variation in our material, and we suggest that the present reference values be adjusted.
Comparative Aluminium Mobilizing Actions of Several Chelators in Aluminium-Loaded Uraemic Rats
Authors: Gómez M. , Domingo J.L. , del Castillo D. , Llobet J.M. , Corbella J. 
Published: December 2008

The relative effectiveness of deferoxamine (DFO), 1,2-dimethyl-1,3-hydroxypyrid-4-one (L1), and citric and succinic acids in mobilizing and promoting excretion of aluminium (Al) were compared in female uraemic rats which had previously received aluminium nitrate nonahydrate i.p. in a daily dose of 45 mg kg-1for 3 weeks (5 days/week). Chelators were administered s.c. at doses equal to one-eighth of their respective LD50for five days. L1 was also given p.o. in doses of 200 mg kg-1day-1. Total urines were collected 24 h after each chelator administration. Total urinary Al excreted over the 5-day period, expressed as mg kg-1, were: controls, 3.4; DFO-treated, 4.5 (P<0.05); citric acid-treated, 3.7; and succinic acid-treated, 2.7. Although the daily amounts of Al excreted into urine by L1-treated rats were significantly higher ( P<0.001) than those of the controls, most animals died during the period of treatment.Measurements of Al in selected tissues 24 h after the last administration of each chelator revealed that none of the compounds significantly altered the Al concentration in bone, kidney, and brain, whereas only DFO and succinic acid significantly reduced the levels of Al in spleen. Moreover, L1 (given s.c. or p.o.) and citric acid treatment led to a significant reduction in the liver Al burden. These results indicate the need for further investigations to determine the toxicity and the therapeutical safety margins of L1.
Dextran Sulphates Protect Porcine Arterial Endothelial Cells from Free Radical Injury
Authors: Hiebert Linda M. , Liu Ji-Min 
Published: December 2008

1 The ability of dextran sulphate to protect cultured porcine arterial endothelial cells injured by addition of xanthine and xanthine oxidase (X/XO) or hydrogen peroxide to cell medium was examined using a variety of drug preparations. Cell damage was assessed by determining cell viability (by trypan blue exclusion) and release of lactate dehydrogenase into the medium. 2 Dextran sulphates of average molecular weight (Mr) 5000, 8000 (hydrogenated or unhydrogenated) at 0.05, 0.5, 5 and 50 μg ml-1 medium, added 24 h prior to X/XO, protected cells, whereas dextran sulphate Mr 500,000 was protective only at 0.5 μg ml-1. 3 None of the dextran sulphates used showed any toxic effect on cells in concentrations up to 500 μg ml-1 medium. 4 When the duration of pretreatment with dextran sulphate Mr 8000 was varied, 6 h was required for a protective effect on cells damaged by X/XO, which was enhanced with durations of 16 and 24 h. 5 Dextran sulphates had a similar protective effect on cells damaged by hydrogen peroxide. 6 This study suggests that dextran sulphates may prevent conditions resulting from free radical injury.
Effects of Lead Poisoning of Rats During Pregnancy on the Reproductive System and Fertility of their Offspring
Authors: Coffigny Hervé , Thoreux-Manlay Annick , Pinon-Lataillade Ghislaine , Monchaux Georges , Masse Roland , Soufir Jean-Claude 
Published: December 2008

1 The effects of lead poisoning during pregnancy were tested on female Sprague-Dawley rats that inhaled 5 mg m-3 lead oxide for 13 days during gestation. At the end of gestation, the respective blood lead levels of dams and fetuses were 71.1 and 83.2 μg 100 ml-1, indicating lead poisoning. 2 In the 90 day-old male offspring of the exposed dams, testis weight and histology, and epididymal weight and sperm reserve, were all similar to those of control males. Spermatozoa mobility and morphology were normal. 3 Also similar to control values were the pituitary weight in these male offspring, their plasma FSH, LH and testosterone levels, and the weight of their ventral prostate and seminal vesicles, the targets of the sexual hormones. 4 When male and female offspring of exposed dams were mated, their fertility was normal, with no increase in prenatal death or malformations, and no changes in the size or sex ratio of litters. 5 These results indicate that, under our experimental conditions, lead oxide inhalation by rats during pregnancy did not perturb reproductive function in their male offspring.
Interaction of Nitrobenzoates with Haemoglobin in Red Blood Cells and a Haemolysate
Authors: Norambuena E. , Videla L.A. , LisSi E.A. 
Published: December 2008

Haemoglobin, either in the intact red blood cells or in their haemolysate, readily reacts with mono- and di-nitrobenzoates. For all the nitroaromatics considered, the rate of the process is faster in the haemolysate than in the whole red blood cell. At low (< 8 mM) concentrations, almost quantitative production of methaemoglobin is observed and the process follows second order kinetics. At higher concentrations, the kinetics become complex and other haemoglobin derivatives are produced.The bimolecular rate constants obtained at low substrate concentrations show little relationship to the nitroaromatic reduction potential. The data indicate that mono-nitrobenzoate derivatives are very active in oxidizing haemoglobin in in vitro erythrocyte suspensions, the activities being similar to that of 3,5-dinitrobenzoate. The measured reactivity follows the order m-nitrobenzoate > 3,5-dinitrobenzoate > p-nitrobenzoate > o-nitrobenzoate and the reactivity of all the compounds is considerably larger than that of nitrobenzene. The present results constitute the first kinetic data bearing on the reactivity of nitroaromatics with haemoglobin, both free and incorporated in the intact red cell. Furthermore, they indicate that the interaction of the nitroaromatics with haemoglobin, leading to total oxidation and transformation, in spite of the total disruption of the membrane, does not produce significant lipid-peroxidation, as measured by chemiluminescence emission, production of TBA reactive material and oxygen consumption.
Human Placental Mast Cells as an In Vitro Model System in Aspects of Neuro-Immunotoxicity Testing
Authors: Purcell W.M. , Atterwill C.K. 
Published: December 2008

1 In both the developing and adult nervous systems, nerve growth factor (NGF) influences neuronal survival, differentiation and recovery following insult,2 The effect of NGF upon human placental mast cells (HPMC) was investigated, since it is known that rodent mast cells express a functional receptor for NGF and secrete histamine upon challenge with this neurotrophic factor. Furthermore, human placental tissue contains a significant amount of NGF and expresses a NGF receptor.3 HPMC were shown to secrete histamine in a concentration dependent manner in response to NGF (0.001-10.0 μg ml-1) in the presence of the lipid cofactor phosphatidylserine (10.0 μg ml-1).4 NGF induced histamine release from isolated HPMC with an EC50of 0.1 μg ml-1NGF and maximal secretion of total cellular histamine of 22.3 ± 3.4% at 3.0 μg ml-1.5 The response was shown to be a secretory process, dependent upon the presence of exogenous calcium ions and to be pH- and temperature-sensitive.6 HPMC are suggested to be a suitable primary cell model for use in aspects of in vitro toxicity testing, in terms of assessing the neuro-immunotoxic potential of neurotrophic therapeutics. In addition, mechanistic studies concerning those xenobiotics which may exert their neurotoxic effect via interaction with neurotrophic factors and, or their receptors, may be studied in this human cell model.
The Use of Human Lung Slices in Toxicology
Authors: Fisher Robyn L. , Smith Mary S. , Hasal Steven J. , Hasal Katherine S. , Gandolfi A. Jay , Brendel Klaus 
Published: December 2008

1 Successful use of agar-filled precision-cut rat lung slices in dynamic organ culture prompted the use of this technology with human lung. 2 The larger tissue mass of a human lung required that the trachea be cannulated with a balloon catheter and subsequently inflated with 4 liters of warm agar/medium mixture and then cooled before being precision-cut into 500 μm thick slices. 3 To characterize the human lung slices, viability and the effects of acrolein and nitrofurantoin were assessed over a period of 24 h using protein synthesis and nonprotein sulfhydryl content. 4 Control human lung slices synthesized protein at a linear rate and maintained a stable nonprotein sulfhydryl content for 24 h. 5 Slices incubated with acrolein exhibited no significant decrease in protein synthesis or nonprotein sulfhydryl levels until 24 h. 6 Incubation with nitrofurantoin exhibited a definite time- and dose-dependent inhibition of protein synthesis, and depletion of the cellular thiol pool. 7 These results indicate that this human lung tissue slice system may be used as an in vitro model to identify and screen pneumotoxicants.
The Effect of Activated Charcoal on the Absorption and Elimination of Astemizole
Authors: Laine Kari , Kivistö Kari T. , Neuvonen Pertti J. 
Published: December 2008

1 The effect of activated charcoal on the absorption and elimination of astemizole and its metabolites was studied in healthy volunteers. 2 Subjects were divided into three groups containing seven subjects each. One group received 30 mg of astemizole with water only (control) and another group with 25 g of activated charcoal. The third group received multiple doses (12 g) of charcoal from 6 h onwards twice daily for 8 days. The concentrations of astemizole and its metabolites in plasma were measured by radioimmunoassay for 192 h. 3 Activated charcoal, administered immediately after astemizole ingestion, reduced the absorption of astemizole by 85% (P<0.001). Multiple doses of activated charcoal, administered throughout the period of astemizole elimination, had no significant effect on the rate of elimination or the area under the curve from 0 to 192 h. 4 The absorption of astemizole from the gastrointestinal tract can be effectively prevented with activated charcoal. Because astemizole is rapidly absorbed, charcoal should be administered as soon as possible in acute astemizole poisoning. Multiple doses of charcoal do not seem to shorten the elimination half-life of astemizole.
Suicidal Inhalation of Vehicular Exhaust in the Lothian and Borders Region of Scotland
Authors: Busuttil A. , Obafunwa J.O. , Ahmed A. 
Published: December 2008

1 A 6-year retrospective study of the features of 79 consecutive completed suicides from exhaust fume inhalation (SEFI) in the Lothian and Borders region of Scotland was conducted. Full forensic autopsies with histological and toxicological studies were carried out. 2 The mean incidence is 2.0/100,000 population (M=3,7; F=0,4; P<>0.001); increasing since 1990. The age peak is in the 35-44 years age group (especially among males) and a significant ( P<0.001) proportion reside in rural areas. 3 SEFI is significantly ( P<0.05) higher during spring and summer; outdoor locations are prevalent during summer. 4 Most (75.6%) of the victims were in current employment. Psychiatric illness (30.7%), problems in marriage or relationships (28.2%) and financial difficulties (16.7%) were the major associated socio-medical factors. 5 The mean carboxyhaemoglobin (COHb) saturation was 74 ± 11.2%; fatal COHb saturation levels were still detectable in severely decomposed bodies. The blood alcohol concentration (BAC) in 37 of the victims ranged from 14-397 mg dl-1. No significant correlation exists between COHb saturation and the victim's age or BAC. 6 Attempts to reduce the incidence of SEFI must be directed principally to dealing with associated socio-medical problems. The reduction of the potential of vehicles to produce carbon monoxide and of directing exhaust fumes into the interior of the vehicle are important secondary preventative measures.