bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Severity Indexes of Patients with Paraquat Poisoning
Authors: Suzuki Kouichiro , Takasu Nobukatsu , Arita Seizaburo , Ueda Akinori , Okabe Toru , Ishimatsu Shinichi , Tanaka Shigeru , Kohama Akitsugu 
Published: December 2008

1 Three indexes for evaluating the severity of paraquat poisoning based on plasma-paraquat concentration are presently in use; the curves of Proudfood et al. and Scherrmann et al. and the SIPP. Their effectiveness in determining the prognosis of patients with paraquat poisoning was evaluated. 2 To determine which index was more accurate, contingency tables of the three indexes were obtained and compared; Proudfoot's curve vs the SIPP Scherrmann's curve vs the SIPP. Proudfoot's curve and the SIPP were applied to patients admitted within 24 h after intoxication. Scherrmann's curve and the SIPP were applied to patients admitted more than 24 h after intoxication. The proportions of patients with true positive and true negative results to total patients were compared by a ratio test. 3 Proudfoot's curve was found to be more accurate than the SIPP for predicting the prognosis of patients admitted within 24 h (P < 0.05). No significant difference, however, was noted between Scherrmann's curve and the SIPP in determining the prognosis of patients admitted after more than 24 h. 4 In conclusion, Proudfoot's curve proved a better index for predicting the outcome of patients who were admitted within 24 h. However, for the prognosis of patients admitted more than 24 h after the ingestion of paraquat, further study is required.
Distribution of Ethylene Oxide in Human Blood and its Implications for Biomonitoring
Authors: Föst U. , Hallier E. , Ottenwälder H. , Bolt H.M. , Peter H. 
Published: December 2008

The distribution of radioactivity following the incubation of human blood with radiolabelled ethylene oxide was investigated in vitro. After incubation, the individual blood samples were separated into lymphocytes and high (Mr > 10,000) and low (Mr < 10,000) molecular fractions of erythrocyte cytoplasm and blood plasma. The radioactivity was determined in each sample by liquid scintillation counting. In erythrocyte cytoplasm, the distribution of radioactivity showed marked interindividual differences and two distinct groups could be distinguished. The coincidence of these groups with 'conjugators' and 'non-conjugators', in terms of the enzymatic conjugation of methyl halides to glutathione in erythrocytes, suggests a common principle, such as enzyme polymorphism. Such polymorphism has been described for glutathione S-transferase μ in the human liver, an enzyme that efficiently conjugates epoxides. In the other blood compartments, the interindividual differences were either less significant or were not detectable. Binding products with various macromolecules in blood, such as haemoglobin or lymphocyte DNA, are being discussed as biological monitors for occupational exposure to ethylene oxide. The observation that erythrocytes exhibit interindividual differences as described above make binding products with haemoglobin less suitable for biological monitoring of ethylene oxide exposure than, for example, DNA adducts in lymphocytes.
Oral Pharmacokinetics of Fluazifop-Butyl in Human Volunteers
Authors: Woollen B.H. , Hart T.B. , Batten P.L. , Laird W.J.D. , Davies D.S. , Dollery C.T. 
Published: December 2008

1 Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2 The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3 The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.
Effects of Combined Exposure to Aluminium and Ethanol on Aluminium Body Burden and some Neuronal, Hepatic and Haematopoietic Biochemical Variables in the Rat
Authors: Flora S.J.S. , Dhawan Mamta , Tandon S.K. 
Published: December 2008

The effects of the daily administration of aluminium (25 mg kg-1, orally), ethanol (10% v/v, in drinking water) or both to adult rats, for 6 weeks, on the amount of aluminium present in the tissues and the functioning of brain biogenic amines, hepatic and serum transaminases and some haematopoietic variables were investigated. Ethanol alone was seen to inhibit the activity of δ-aminolevulinic acid dehydratase (ALAD), while aluminium alone elevated the activity of blood ALAD. However, aluminium and ethanol combined produced a more pronounced inhibition of blood ALAD and hepatic glutamic pyruvic transminase (GPT) than either aluminium or ethanol alone. Simultaneous exposure to aluminium and ethanol also produced a significant elevation in urinary δ-aminolevulinic acid (ALA) blood zinc protoporphyrin (ZPP), serum glutamic oxaloacetic transaminase (GOT) and brain homovanillic acid (HVA), and a depletion in brain dopamine (DA) and 5-hydroxytryptamine (5-HT) levels, when compared to rats given aluminium alone. The concentration of aluminium in the blood and liver was significantly higher in rats exposed to both aluminium and ethanol than in those exposed to aluminium alone. Thus the consumption of alcohol may increase the rat's susceptability to certain effects of aluminium.
Studies on the Mutagenicity of a Zinc Oxide-Hexachloroethane Smoke
Authors: Clode S.A. , Riley R.A. , Blowers S.D. , Marrs T.C. , Anderson D. 
Published: December 2008

1 A suitable method has been developed for generating atmospheres of zinc oxide/ hexachloroethane smoke (ZnHCE). 2 The smoke was investigated using the Ames test and the micronucleus assay. 3 It was weakly mutagenic to the bacteria, but in the bone marrow no increases in micronuclei were detected up to toxic levels of the smoke. 4 The method used here could be applied to other pyrotechnic mixtures which give rise to complex mixtures of products.
The Effect of Therapeutic Doses of Paracetamol on Sulphur Metabolism in Man
Authors: Blackledge H.M. , O'Farrell J. , Minton N.A. , McLean A.E.M. 
Published: December 2008

1 This study was designed to investigate the effect of prolonged paracetamol intake on sulphur metabolism in patients. Six patients, taking paracetamol in doses of 2-4 g d-1and one taking 12 g d-1took part in the study. Daily (24-h) collections of urine, and also plasma samples from these patients were analysed and in one case a study with additional methionine was performed.2 The patients showed variable decrease in urinary output of inorganic sulphate but moderately raised plasma levels of inorganic sulphate.3 Paracetamol metabolism was characterized by dominance of the glucuronidation pathway with the increase of the administered dose of paracetamol. Methionine added to the diet did not change this metabolic pattern. None of the subjects produced more than 0.6 mmol h-1paracetamol sulphate while total sulphur excretion was 7.5-26.7 mmol d-1.4 Volunteers taking 3 g d-1paracetamol were also studied.5 In persons taking a normal western diet containing over 20 mmol d-1sulphur amino-acids paracetamol metabolism will not lead to sulphur amino-acid depletion even if high daily doses are used.
Non-specificity of Clinical Signs and Symptoms Caused by Environmental Chemicals
Authors: Grandjean P. , Sandoe S.H. , Kimbrough Renate D. 
Published: December 2008

1 A review of the scientific literature revealed that 220 environmental chemicals had caused documented systemic toxicity in humans. This number is relatively small compared to the large number of industrial chemicals in the environment. 2 A total of 149 of these chemicals were verified as neurotoxins, thus emphasizing the sensitivity of this target organ. Despite the exclusion of chemicals that cause airway irritation only, 99 chemicals caused adverse effects on the respiratory system. Toxicity to the liver, kidneys and blood forming organs was less frequent. 3 Most of the individual clinical effects had a very low specificity in cases of human intoxication. Of 80 major signs and symptoms, 17 had only a single documented chemical aetiology. However, the combination of two or more signs or symptoms was found to provide an improved guidance to aetiological diagnosis. The paucity of specific signs and symptoms is probably one of the reasons that only 220 environmental chemicals have been documented as causes of human disease.
Effects of a Cholecystokinin Receptor Antagonist on Rat Exocrine Pancreatic Response to Raw Soya Flour
Authors: Sundaram S. , Dayan A.D. 
Published: December 2008

1 Raw soya flour (RSF) in the diet induces pancreatic hypertrophy and hyperplasia in the rat, changes ascribed to production of a high circulating level of cholecystokinin (CCK) due to inhibition of trypsin in the duodenum. Prolonged ingestion results in pancreatic adenomas and carcinomas.2 L-364, 718, a potent, highly specific CCK antagonist was used to investigate the short-term role of CCK.3 In rats fed 50% RSF and L-364, 718 5 mg kg-1p.o. twice daily for 4 d, there was inhibition of pancreatic hypertrophy and hyperplasia, which is further evidence that peripherally-acting CCK plays a major role in the generation of RSF-mediated changes in the pancreas.
The Need for a Control Animal Pathology Database: An International Survey
Authors: McAuslane J.A.N. , Lumley C.E. , Walker S.R. 
Published: December 2008

1 The sensitivity of long-term toxicity tests is impaired due to the 'background noise' of spontaneous lesions which are unrelated to treatment. 2 The need for a comprehensive source of computerized information concerning the occurrence and incidence of spontaneous lesions in control animals has been highlighted by initiatives in Europe and the USA. It is, however, essential to identify the potential users, and the type of information required for such a database to be of value. 3 This information has been acquired following an international survey of the pharmaceutical industry in Europe, Japan and the USA, including responses from 48 toxicologists and toxicopathologists representing 38 company groups. 4 Thirty-eight respondents indicated that they would use a historical control database that was regularly updated with the majority of respondents suggesting that they currently use external sources (Breeder's data, the literature, other companies) occasionally to acquire information on control animal pathology data. 5 The majority (94%) of the respondents indicated that a control animal database should contain information on both neoplastic and non-neoplastic lesions for use in evaluating long-term studies, in particular carcinogenicity studies. 6 The survey confirms the need for a historical control animal pathology database wider then those currently available.
Changes in Arterial Oxygen Tension after Gastric Lavage for Drug Overdose
Authors: Jorens Philippe G. , Joosens Eric J. , Nagler Jan M. 
Published: December 2008

1 Changes in arterial oxygen tension after gastric lavage were investigated in a prospective study of 55 patients admitted for drug overdose. 2 A significantly greater decrease was observed in smokers compared to non-smokers. 3 A correlation was found between the tricyclic antidepressant serum level and the observed oxygen tension decrease. 4 The usefulness, as well as the safety of the lavage procedure, in managing tricyclic antidepressants overdoses is controversial.
Computer Prediction of Possible Toxic Action from Chemical Structure; The DEREK System
Authors: Sanderson D.M. , Earnshaw C.G. 
Published: December 2008

1 The development of DEREK, a computer-based expert system (derived from the LHASA chemical synthesis design program) for the qualitative prediction of possible toxic action of compounds on the basis of their chemical structure is described. 2 The system is able to perceive chemical sub-structures within molecules and relate these to a rulebase linking the sub-structures with likely types of toxicity. 3 Structures can be drawn in directly at a computer graphics terminal or retrieved automatically from a suitable in-house database. 4 The system is intended to aid the selection of compounds based on toxicological considerations, or separately to indicate specific toxicological properties to be tested for early in the evaluation of a compound, so saving time, money and some laboratory animals and resources.
Self-poisonings with Psychopharmacological Agents in Zagreb
Authors: Miličević G. , Prpić H. 
Published: December 2008

1 A 5-year retrospective study of 1743 episodes of self-poisoning in 1608 adult patients, was undertaken to determine the frequency of self-poisoning with psychopharmacological agents, the frequency of each toxic agent usage and the epidemiological characteristics of the poisoned population. 2 The annual incidence of self-poisoning in Zagreb was 38.7 per 100 000 adult inhabitants. The anxiolytic-antipsychotic-antidepressant usage ratio was 8.8:1.5:1.0 in total self-poisoning, whereas it was 4.9:1.5:1.0 in patients with a previous history of self-poisoning. The use of anxiolytics decreased and the use of antidepressants increased during the 5 years. 3 The female—male ratio was 3.8:1 and 77% of self-poisoned persons were aged 15-44 years. The incidence of self-poisoning was 74% higher in the urban than in the rural population. The proportion of self-poisoned persons was 204% higher among the unemployed than in the population as a whole. There were 76% more repetitors among highly educated and 43% fewer repetitors among students than in the general population. The use of antipsychotics was 120% higher in males than in females. The use of antidepressants was 107% higher in the highly educated. 4 The increased use of antidepressants in self-poisoning is an alarming signal and caution in their prescription seems to be indicated.
Drug Interaction between Rifampicin and Cotrimoxazole in Patients with Tuberculosis
Authors: Bhatia R.S. , Uppal R. , Malhi R. , Behera D. , Jindal S.K. 
Published: December 2008

1 Patients ( n = 15) who were admitted with complications of tuberculosis, were given antitubercular therapy (ATT) with rifampicin (RIF), for a minumum period of 15 d, and cotrimoxazole (CTZ), concurrently, for 5-10 d. 2 The serum RIF levels were measured before the start of CTZ treatment and at the end of its administration. 3 The plasma half-life ( t½) of RIF increased significantly from 1.92 ± 0.57 h to 2.31 ± 0.134 h after CTZ treatment. 4 The mean serum levels of RIF increased significantly at 4 and 6 h after CTZ administration.
Analysis of the Immunotoxic Effects of Xenobiotics
Authors: Procházková J. 
Published: December 2008

1 Current problems in immunotoxicology are reviewed with special attention to the sensitivity of the immune system to the effects of xenobiotics. 2 Sensitivity of target cells, route of exposure, dosage, mechanism of action and response of the immune system are discussed as the main factors responsible for the ultimate effects of drugs and chemicals. 3 The methodology of immunotoxicology is divided into two main steps: preclinical screening and the monitoring of exposed persons. 4 Conclusions are prescribed about future tasks in human immunotoxicology.
Induction of DNA Strand Breaks in Peripheral Lymphocytes by Soluble Chromium Compounds
Authors: Gao M. , Binks S.P. , Chipman J.K. , Levy L.S. , Braithwaite R.A. , Brown S.S. 
Published: December 2008

1 Incubation of human lymphocytes with sodium dichromate (CrVI) at 37°C for 3 h resulted in a dose-dependent increase in DNA strand breaks without concurrent cytotoxicity. In contrast, chromium acetate hydroxide (CrIII) failed to induce DNA strand breaks at sub-cytotoxic concentrations. 2 DNA strand breaks were also detected in the peripheral lymphocytes of Wistar rats, 24 h after intratracheal instillation of sodium dichromate (1.3 and 2.5 mg kg-1 ). Instillation of chromium acetate hydroxide (up to 21.8 mg kg -1) failed to induce DNA strand breaks in peripheral lymphocytes. In accord with previous studies, hexavalent chromium was found to be more readily absorbed from the lungs into the peripheral blood than chromium in its trivalent form. 3 The results of this study indicate that fluorometric analysis of DNA unwinding (FADU) in peripheral lymphocytes might be a convenient method of measuring an important biological effect of chromium in occupationally-exposed workers.
Studies on the Disposition and Metabolism of Hydrazine in Rats in vivo
Authors: Preece Nicholas E. , Ghatineh Simin , Timbrell John A. 
Published: December 2008

1 Rats were given various doses of hydrazine orally and their plasma and liver hydrazine levels were determined (at various times up to 270 min after dosing) by gas chromatography/ mass spectrometry.2 The increase in the peak plasma level and in the area under the plasma concentration-time curve (AUC) were not directly proportional to the dose.3 The ratio of plasma to liver hydrazine varied with dose suggesting saturation of an uptake mechanism might be occurring.4 In a separate experiment hydrazine was still detectable in the plasma and liver 24 h after dosing with hydrazine i.p.5 Rats were given the same doses of hydrazine and urine was collected for 24 h after dosing and assayed for hydrazine and acetylhydrazine. The proportion of hydrazine and acetylhydrazine excreted declined with dose.6 Liver samples were taken for histopathological examination 96 h after dosing. Only after the highest dose (81 mg kg-1) was there evidence of fatty liver, 96 h after a single dose, and a reduction in both liver and body weight.
The Effect of Brassica Vegetable Consumption on Caffeine Metabolism in Humans
Authors: McDanell R.E. , Henderson L.A. , Russell K. , McLean A.E.M. 
Published: December 2008

Ten healthy volunteers were used in two studies investigating the effect of short-term Brassica consumption on caffeine metabolism. In the first study volunteers were given three Brassica-containing meals, the last one 3 h prior to caffeine administration. In the second study volunteers were given two Brassica-containing meals and then fasted overnight before caffeine administration.In both studies the mean plasma half-life of caffeine was reduced by approximately 20% following a Brassica diet, suggesting that Brassica vegetables stimulate caffeine metabolism.When caffeine was given 3 h after the last meal, plasma caffeine concentrations over 6 h, were increased by up to 27% on the Brassica diet compared to controls. This may be due to a transient increased permeability of the intestine to caffeine, immediately following Brassica consumption. This effect was not seen in the second study where there was a 12-h period between the last meal and caffeine administration.There was large interindividual variation in the effect of the Brassica diet on caffeine metabolism.
Determination of Heavy Metals in Human Liver
Authors: Bona M.-A. , Castellano M. , Plaza L. , Fernandez A. 
Published: December 2008

The levels of Cr (2.49±0.89 ppm), Mn (5.08 ± 1.60 ppm), Ni (1.81±0.95 ppm) and Pb (4.43 ± 3.12 ppm) were measured in dessicated liver from 44 cases of sudden traumatic death considered as representative of the general population in our area, after ruling out the presence of any underlying disease. Atomic absorption spectrophotometry and electrothermal atomitazion was carried out after hot, acid digestion, of the dessicated samples. After cancelling the influence of age and cause of death, a significant, positive correlation between Cr/Mn (P = 0.0009; R = 0.493) and Cr/Ni ( P = 0.0245; R = 0.347) levels was found.
Dose Selection for Toxicity Studies: A Protocol for Determining the Maximum Repeatable Dose
Authors: Spurling N.W. , Carey P.F. 
Published: December 2008

1 A three-stage protocol is described for a dose-ranging study which defines the maximum repeatable dose (MRD) and provides a preview of the toxicology of new, pharmacologically active, substances before commencing the first formal regulatory toxicity studies, usually of 2 or 4 weeks duration. 2 Additionally, a range of toxicokinetic (TK) data relevant to protocol design for formal studies is generated. 3 Stage A is a dose incrementation process in which the MRD is provisionally determined and basic TK values generated. 4 In stage B the animals are dosed daily for at least 7 d, the MRD is substantiated and a wider range of TK data obtained. 5 In stage C, each of the dose levels identified for a formal study is administered once to investigate the relationship of doses to TK data. 6 This protocol can be completed using as few as 24 rats or six dogs (or primates). 7 Selection of dose levels for the first formal studies can be greatly aided by the results of a well-designed dose-ranging study including TK data. 8 For particularly toxic substances, the findings of studies based on this protocol have frequently been sufficiently clear to warrant early termination of their development.
Effect of Glycol Ethers on Plasma Osmolality
Authors: Browning Randall G. , Curry Steven C. 
Published: December 2008

1 Glycol ethers and their alkoxyacetic acid metabolites produce a linear increase in plasma osmolality with increasing plasma concentration.2 This change in osmolality may be too small to be clinically useful at concentrations expected in cases of acute human glycol ether poisoning.
Efficacy of Whole Bowel Irrigation Using Solutions with or without Adsorbent in the Removal of Paraquat in Dogs
Authors: Mizutani Taro , Yamashita Mamoru , Okubo Naomitsu , Tanaka Makoto , Naito Hiroshi 
Published: December 2008

1 The efficacy of whole bowel irrigation with a solution containing either polyethylene glycol (PEG) with electrolyte or an adsorbent (Kayexalate™) with a cathartic (sorbitol) was investigated in 18 dogs who had been given 250 mg kg-1paraquat dichloride via a jejunal tube to eliminate the influence of gastric absorption.2 Plasma paraquat concentrations 2 and 3 h after the initiation of bowel irrigation and at the end of the study (5 h later) were significantly lower in the bowel irrigation groups than in the control (no bowel irrigation) group.3 The total body clearances of paraquat in the bowel irrigation groups were significantly greater than in the control group.4 There were no significant differences between the two different irrigation solution groups in plasma paraquat concentration, the area under the plasma concentration time curve and the total body clearance.5 In the PEG with electrolyte group, about 70% of the administered dose of paraquat was removed by means of bowel irrigation (n=4).6 The adjunction of the adsorbent had no beneficial effects.7 Haemodynamic changes associated with whole bowel irrigation were unremarkable except that right atrial and pulmonary arterial pressures were elevated in the latter part of the study.