bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity of a Novel HMG-CoA Reductase Inhibitor in the Common Marmoset (Callithrix jacchus)
Authors: Owen K. , Pick C.R. , Libretto S.E. , Adams M.J. 
Published: December 2008

1 GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1day-1were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7,5 and 20 mg kg-1day-1for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days,2 Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes, There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1day-1and above.3 Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment.4 Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity.5 Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function.6 HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.
Interindividual Variation in Biotransformation and Cytotoxicity of Bromobenzene as Determined in Primary Hepatocyte Cultures Derived from Monkey and Human Liver
Authors: Mennes W.C. , van Holsteijn C.W.M. , van Iersel A.A.J. , Yap S.H. , Noordhoek J. , Blaauboer B.J. 
Published: December 2008

1 Bromobenzene-evoked hepatotoxicity resulting from cytochrome P450-mediated epoxidation has been studied extensively in rodents in vivo and in rodent hepatocytes. In this paper we present data concerning the formation of bromphenols, glutathione (GSH) depletion and cytotoxicity observed in primate hepatocytes in primary culture after exposure to bromobenzene (BrB).2 After pre-incubation for 2 or 24 h, hepatocytes were exposed to BrB in concentrations up to 2 mM for 4 or 24 h.3 In both human and cynomolgus monkey hepatocytes BrB cytotoxicity and GSH depletion were found after exposure to 2 mM BrB. The degree of the observed effects was not influenced by the duration of pre-incubation and/or exposure periods.4 Major inter-individual differences were observed, which could not be attributed to differences in cytochrome P450-mediated bioactivation rates. This suggests that the variation in individual susceptibility to BrB may be related to interindividual differences in the activity of de-activating (metabolic) pathways.5 The study of the background of these interindividual differences may contribute to a more complete understanding of the factors ruling sensitivity to BrB or related chemicals.
Infiluence of Lindane and Paraquat on Oxidative Stress-Related Parameters of Erythrocytes In Vitro
Authors: Bainy Afonso C.D. , Silva Marcia A.S. , Kogake Mariza , Videlal Luis A. , Junqueira V.B.C. 
Published: December 2008

1 The influence of lindane and paraquat on oxidative stress-related parameters of the red blood cell was studied in vitro.2 Lindane addition did not modify either the t-butyl hydroperoxide-induced oxygen uptake of the erythrocytes and the induction time preceding it, or the activity of catalase, superoxide dismutase, glutathione peroxidase and glucose 6-phosphate dehydrogenase, in conditions of comparable levels of haemoglobin and methaemoglobin.3 Red blood cells exposed to paraquat exhibited a concentration-dependent decrease in the t-butyl hydroperoxide-induced oxygen consumption and increments in either the induction period or in the activity of catalase and glucose 6-phosphate dehydrogenase, with no changes in superoxide dismutase activity and a small decrement in that of glutathione peroxidase.4 These data indicate that lindane does not interfere with the oxidant status of the erythrocyte, while paraquat addition leads to an increment in the anti-oxidant capacity of the red blood cell.
No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats
Authors: Meulenbelt J. , van Bree L. , Dormans J.A.M.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 N-acetylcysteine (NAC) was administered intravenously to study its effect on biochemical variables in broncho-alveolar lavage fluid in acute NO2 intoxicated rats. It was decided to start the intravenous administration of NAC 24 h before the exposure to NO2 to induce higher intracellular glutathione (GSH) levels in lung cells of NAC-treated rats compared to not NAC-treated rats. Because, on theoretical grounds, the therapeutic effect of NAC may be expected to be especially marked during the first 24 h after exposure, the rats were observed for a period of 24 h and were then killed for investigation. A loading dose of 85 mg kg-1 h-1 or 170 mg kg -1 h-1 was followed by a continuous infusion (until autopsy) with a dose of 225 mg kg-1 24 h-1 or 450 mg kg -1 24 h-1 respectively. 3 Twenty four hours after exposure to 175 ppm NO2 (1 ppm is 1.88 mg m-3) for 10 min, NAC did not reduce the increase of variables in bronchoalveolar lavage fluid which reflect the severity of lung damage. 4 The protein and albumin concentration and the activities of angiotensin converting enzyme and alkaline phosphatase in broncho-alveolar lavage fluid after NO 2 exposure were even more increased in the NAC-treated than in the saline-treated rats, but none of the differences was statistically significant. 5 In sham exposed rats no effect of NAC was observed.
Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure
Authors: Groth G. , Freundt K.J. 
Published: December 2008

1 A continuous 5 h-exposure to approximately 440 ppm tert-butyl acetate in air (via a tracheal canule) resulted in continuously increasing concentrations of tert-butyl acetate and tert-butyl alcohol (metabolite of tert-butyl acetate) in the blood of rats. 2 This accumulation of tert-butyl acetate and tert-butyl alcohol was reproduced during a continuous exposure to about 900 ppm tert-butyl acetate in air over a period of 4 h and 15 min. After the inhalation approximately 50% of the blood level of tert-butyl acetate decreased within 45 min, but that of tert-butyl alcohol remained unchanged at a high level. 3 The accumulation of tert-butyl acetate and tert-butyl alcohol should be relevant for the health risk assessment at the workside.
Toxicity of Cisplatin and Mercuric Chloride in Human Kidney Cortical Slices
Authors: Fisher Robyn L. , Sanuik Jeffery T. , Gandolfi A. Jay , Brendel Klaus 
Published: December 2008

1 Organ specific toxicity such as nephrotoxicity is often investigated with the use of in vivo or in vitro animal models.2 It would be beneficial if these findings could be verified in a human in vitro system which utilizes non-transplantable human kidneys.3 Non-transplantable human kidneys were decapsulated, cut in half along the long axis, cores made perpendicular to the hemisphere, and precision-cut renal cortical slices produced.4 These human kidney slices were incubated for 3, 6, 12, 18 and 24 h, viability assessed using intracellular K+ content, protein synthesis and organic ion transport and the potential nephrotoxicity of cisplatin (0.25, 0.5 and 1.0 mM) and mercuric chloride (10, 50 and 100 μm) on these slices were examined.5 Control human kidney slices were viable for up to 24 h using all viability parameters while a dose-and time-dependent toxic response was seen using both cisplatin and mercuric chloride.6 Cisplatin was more nephrotoxic in this human in vitro system than in previously investigated in vitro animal systems whereas mercuric chloride was similar in both systems.7 These results indicate that human renal cortical slices are useful in predicting and verifying potentially nephrotoxic compounds in man.
Suspected Paediatric Pesticide Poisoning in the UK, I - Home Accident Surveillance System 1982-1988
Authors: Casey P.B. , Thompson J.P. , Vale J.A. 
Published: December 2008

1 Between 1982 and 1988, 239,350 children under 10 years old attended 20 A & E Departments in England and Wales (22 departments throughout the UK in 1988) as a result of a home accident. 15,144 of 239,350 were suspected cases of poisoning and 514 attendances involved pesticides. 2 501 of 514 children who attended hospital were under 6 years old and 41 % were thought to have ingested a rodenticide, 37% an insecticide or other animal poison, 13% an herbicide or fungicide and 9% other pesticides. 3 Overall 189 of 514 children were admitted to hospital and of these 189 cases 35% were discharged home in less than one day; 94% left hospital within 2 days. 4 Using these data we estimate that over the period of study approximately 1,850 children annually attended an Accident and Emergency Department in the UK with suspected pesticide poisoning and that some 450 were admitted to hospital. However, the morbidity from this cause is low and no deaths from pesticide poisoning have been reported in children in England and Wales for more than two decades.
Suspected Paediatric Pesticide Poisoning in the UK, II — Home Accident Surveillance System 1989-1991
Authors: Thompson J.P. , Casey P.B. , Vale J.A. 
Published: December 2008

1 Between 1989 and 1991, 121,708 children less than 10 years old attended 22 Accident and Emergency (A & E) Departments in the UK as a result of an accident at home; 6,478 of these were cases of suspected poisoning. 2 Two hundred and fifty (124 boys and 126 girls) of 6,478 cases involved pesticides. Forty two per cent of these children were thought to have been poisoned by rodenticides, 33% by a different animal poison, 13% by an herbicide or fungicide, 7% by creosote and 5% by mothballs; a pattern similar to that observed in previous years. 3 Fifty-seven of 250 children (23%) were admitted to hospital. The proportion of children admitted to hospital between 1989 and 1991 is smaller than that observed between 1982-1988 (37%). Forty-six per cent of children were discharged home within one day and 95% within 2 days, whereas between 1982 and 1988 only 35% of children were discharged within one day. No child died during the study confirming the low morbidity. 4 Using these data we estimate that between 1989 and 1991 approximately 1,500 children annually attended an A & E Department in the UK with a diagnosis of suspected pesticide poisoning and that some 350 children were admitted each year.
Prevention of Paraquat Toxicity in Suspensions of Alveolar Type II Cells by Paraquat-Specific Antibodies
Authors: Nian Chen  , Bowles Mark R. , Pond Susan M. 
Published: December 2008

1 The herbicide, paraquat, is accumulated by the energy-dependent polyamine uptake pathway of alveolar type II cells. There it undergoes redox cycling that results in an amplified production of toxic reactive oxygen species and depletion of NADPH and other reducing equivalents. These processes account for the lung being the major target organ for paraquat toxicity.2 We postulated that paraquat-specific antibodies would inhibit the uptake of the herbicide by type II cells and prevent its toxicity. Accordingly, we examined the effects of paraquat-specific monoclonal antibodies and Fab fragments on the uptake, efflux and cytotoxicity of 50 μM paraquat in suspensions of alveolar type II cells isolated from the rat.3 The uptake of paraquat was linear over 40 min. Over this time, the uptake rate was inhibited significantly (% inhibition, 73-89) by IgG (25 or 50 μM) or Fab fragments (50 or 100 μM).4 The apparent efflux rate of paraquat, studied over 16 h, was increased significantly from 0.12 h-1for the control cells in medium to 0.17 h-1by paraquat-specific Fab fragments but was unaffected by the specific IgG.5 Cytotoxicity was determined by measuring the release of51Cr from the cells. The cytotoxicity of 50 μM paraquat was decreased significantly (percent decrease, 56-80%) in the presence of specific antibodies.6 These studies in vitro suggest some potential for immunotherapy in selected cases of paraquat poisoning.
Glutathione Deficiency does not Elevate Susceptibility of Bacteria to the Mutagenicity of Chlorinated Humic Acids
Authors: Ubom G.A. , Chipman J.K. , Hayes M.H.B. 
Published: December 2008

1 Rat liver 9,000 g supernatant protected against the mutagenic effect of chlorinated hydrophilic macromolecular humic acids (CHMA) in Salmonella typhimurium strain TA100. 2 Protection against mutagenicity of CHMA was mediated by glutathione and was partially dependent on glutathione S-transferase activity. 3 In contrast to the above findings, CHMA showed lower mutagenicity in Salmonella typhimurium and Escherichia coli strains of bacteria that are deficient in glutathione compared to their mutagenicity in parental (glutathione-rich) bacterial strains. 4 Glutathione-deficient cells do not provide test systems with elevated sensitivity for the detection of mutagenic chlorinated humic substances.
A hole in our knowledge of ozone toxicity?
Authors: Maynard R.L. 
Published: December 2008

Evidence suggests that allergic disease is becoming more common, particularly in industrialized societies. Two studies of schoolchildren from Aberdeen, Scotland aged 8-13 years were undertaken in 1964 and 1989 using identical questionnaires, and found that the reported prevalence of asthma had risen from 4.1% to 11.9% and eczema from 5.3% to 12%. Indication that air pollution may contribute to this increase has come from several studies. In Japan,allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. Severe asthma also occurs more commonly than mild asthma in children living in polluted areas. Exercise-induced asthma and the use of asthma medication were twice as high in a town near two power stations compared with a non-polluted town. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide. Deterioration in peak flow recordings in asthmatics and exacerbations of symptoms in hay fever sufferers correlate with ambient levels of ozone. Elucidation of the mechanisms by which exposure to air pollutants may influence the frequency of allergic disease or exacerbate symptoms has come from in vitro and in vivo experiments in animals and man. Animals exposed to ozone, sulphur dioxide, nitrogen dioxide and particles from diesel exhaust, together with allergens, show more ready development of allergic sensitization compared with those exposed to allergen alone. The dose of allergen necessary to produce a 20% fall in FEV, (forced volume in 1 second) in mild-asthmatics is reduced by previous exposure to ozone or a mixture of nitrogen dioxide and sulphur dioxide. It has also been suggested that the allergic potency of pollen grains may be increased when they are coated in pollutants. Bronchial and nasal lavage studies have shown that air pollutants can induce an influx of inflammatory cells and proinflammatory cytokines into the respiratory tract. Studies on human epithelial cells cultured to confluence in vitro have indicated that exposure to nitrogen dioxide can decrease ciliary beat frequency which would, in theory, reduce allergen clearance and increase the risk of sensitization. Further, exposure of these cells to either ozone or nitrogen dioxide induces the release of inflammatory mediators, such as leukotriene C4, and proinflammatory cytokines, including granulocyte-macrophage colony-stimulating factor, tumour necrosis factor - α and interleukin-8. This effect can be attenuated by the use of anti-inflammatory drugs.
Human Polymorphonuclear Leukocyte Chemotaxis as a Tool in Detecting Biological Early Effects in Workers Occupationally Exposed to Low Levels of n-HeXane
Authors: Governa Mario , Valentino Matteo , Visanà Isabella , Monaco Francesca 
Published: December 2008

Human polymorphonuclear leukocytes (PMN) were chosen to measure two cellular end points- chemotaxis and respiratory burst - and to verify whether they could function as biomarkers of early effect in detecting occupational exposure to n-hexane of apparently healthy shoe workers, without any electroneuromyographic (ENMG) abnormality. Chemotaxis, but not respiratory burst, was found to be impaired. A negative linear correlation between chemotaxis of PMN of those workers that had been exposed to n-hexane versus 2,5-hexanedione (2,5-HD) urinary concentrations were found. This negative trend is consistent with our previous in vitro experimental findings: it was observed that the progressive addition of 2,5-HD to PMN suspensions inhibited chemotaxis in a dose-dependent mode, while chemiluminescence was not modified. Now we have confirmed in vivo that chemotaxis is more sensitive than the respiratory burst response to 2,5-HD. Such results justify the interest in the behaviour of PMN harvested from workers exposed to n-hexane. Since significant inhibition of chemotactic activity was observed in some workers whose urinary 2,5-HD levels were lower than 5 mg l-1, which is the biological exposure index suggested by ACGIH, this study suggests that PMN chemotaxis may be proposed as a useful biomarker in detecting occupational exposure to low level of n-hexane.
Accuracy of Admission and Pre-autopsy Clinical Diagnoses in the Light of Autopsy Findings: a Study Conducted in Budapest
Authors: Szende B. , Kendrey G. , Lapis K. , Lee P.N. , Roe F.J.C. 
Published: December 2008

Pre- and post-autopsy diagnoses of underlying cause of death were compared in consecutive autopsies on persons aged 30 to 80 years; 1000 from each of two pathology departments in Budapest. Data on admission diagnoses and on contributory causes of death were also analysed. At autopsy, the percentages of deaths by underlying cause were neoplasms (any site) 34.9%, diseases of the circulatory system 40.2%, digestive system 13.8%, endocrine, nutritional, metabolic or immune systems 2.7%, and respiratory system 2.2%. For these five disease groupings, the percentages of cases diagnosed clinically as the underlying cause of death which were confirmed at autopsy were, respectively, 90.9%, 84.0%, 82.9%, 55.2% and 32.5%. Although, out of 697 cases with an autopsy diagnosis of neoplasia as the underlying cause, there were only 61 (8.8%) where neoplasms were not diagnosed clinically as the underlying cause, this conceals the fact that in 130 (18.7%) the two diagnoses differed as to the site of the primary neoplasm (ICD 3 digit code). The fact that 43% of post-mortem diagnoses (ICD major category) of underlying cause are missed on admission, and that 19% are missed clinically, indicates that improved clinical diagnostic procedures have not diminished the need for high autopsy rates. Morbid anatomy needs to be better resourced.
Poisoning due to Savlon (Cetrimide) Liquid
Authors: Chan Thomas Y.K. 
Published: December 2008

1 Seven adult cases of deliberate oral exposure to 'Savlon' liquid (chlorhexidine gluconate 0.3%, cetrimide 3%) are presented. 2 In six patients, the symptoms were relatively mild including nausea, vomiting, sore throat and abdominal pain. 3 One patient who had concomitantly taken 'Dettol' liquid was comatose and hypotensive at presentation and was complicated by aspiration pneumonia and adult respiratory distress syndrome (ARDS). She was ventilated for a total of 10 days and was hospitalised for 5 weeks. 4 The data from this study suggest that symptoms associated with Savlon poisoning are usually mild. When aspirated, Savlon together with 'Dettol' liquid can cause ARDS.
Viper Bites in France: Clinical and Biological Evaluation; Kinetics of Envenomations
Authors: Audebert Françoise , Sorkine Marc , Robbe-Vincent Annie , Bon Cassian 
Published: December 2008

1 A second inquiry was conducted in France to collect more accurate epidemiological, clinical and biological data from patients hospitalized after a viper bite, as well as treatment that they received. Fifty-seven well documented cases were classified in four grades of increasing severity defined according to the clinical signs of envenomation. 2 Local and systemic signs of envenomation appeared during the first 3 h, but the severity of the envenomation was observed to increase during the 12-24 h following bites in 50% of moderate and severe cases. One fatal case was reported. Biological analysis revealed an hyperleukocytosis in patients with moderate and severe envenomations. 3 The average length of hospitalization was of 1.7 ± 1.3 days for patients without signs of envenomation (grade 0) or presenting a minimal envenomation (grade 1), and statistically longer, 6.2 ± 2.9 days, for patients presenting moderate (grade 2) or severe envenomation (grade 3). 4 Levels of venom antigens in serum samples regularly collected during hospitalization were determined by a sandwich ELISA test. The serum venom levels determined during the first 4 h following the bite correlated with the severity of the envenomation when the symptoms were determined at their worst, usually 12-24 h later. In fact, concentrations higher than 20 ng ml-1 predict a moderate or severe clinical evolution. 5 The pharmacokinetics of venom antigens was also investigated during human envenomations. Venom antigens could be detected in the serum of patients as soon as half an hour after the bite, then decreased exponentially during the following hours with an apparent half-life of 8 h, similar in grade 2 and grade 3 patients, indicating that the kinetics of venom antigens in blood is independent of the severity of the envenomation.
Cysteine Esters Protect Cultured Rodent Lung Slices from Sulphur Mustard
Authors: Wilde Paul E. , Upshall David G. 
Published: December 2008

1 In previous studies an in vitro rat lung slice system was used to investigate the metabolic and structural changes after exposure to known lung toxicants. 2 In this study, the same system was used to identify the ability of cysteine esters to protect against sulphur mustard toxicity. 3 The cyclopentyl (CCPE), cyclohexyl (CCHE), isopropyl (CIPE), methyl (CME) esters of cysteine, cystine dimethyl ester (CDME), cysteine (CySH) and N-acetyl cysteine (NAc) were all non-toxic to cultured rat lung slices at 5 mM (equivalent cysteine concentration) after a pretreatment time of 30 min. 4 Pretreatment with the isopropyl, cyclohexyl, cyclopentyl and methyl esters of cysteine at concentrations higher than 1 mM protected against an IC50 of sulphur mustard, however, neither cysteine nor N-acetylcysteine protected. 5 We propose that the extent of protection is directly related to increased levels of intracellular cysteine provided by the esters of cysteine.