bluuebunny/crossref_metadata_2025_split huggingface dataset:
In- Vitro Hepatotoxicity of Three Dichlorobenzene Isomers in Human Liver Slices
Authors: Fisher Robyn , Barr John , Zukoski Charles F. , Putnam Charles W. , Sipes I. Glenn , Gandolfi A. Jay , Brendel Klaus 
Published: December 2008

1 The cytotoxicity of dichlorobenzenes in cultured rat liver slices has previously been shown to be strain specific and biotransformation related. 2 In order to extrapolate animal models to humans, the dichlorobenzenes were incubated with human liver slices to try to clarify their hepatotoxic potential in man. 3 The degree of hepatotoxicity observed with the dichlorobenzenes depended on whether Waymouth's or Krebs-Henseleit was used as the incubation medium. 4 All three dichlorobenzenes (1 mM) produced no significant differences from control when incubated in Waymouth's medium. However, in the Krebs-Henseleit buffer there was a substantial increase in cytotoxicity. 5 In both incubation mediums the dichlorobenzene isomers exhibited the following rank order 1,3-DCB > 1,2-DCB > 1,4-DCB. 6 1,2-dichlorobenzene hepatotoxicity was blocked by metyrapone, 1,3-dichlorobenzene toxicity was blocked by SKF 525-A and neither one of these inhibitors could block the 1,4-dichlorobenzene cytotoxicity. 7 The use of human liver tissues to evaluate potential toxicants merits consideration since the hepatotoxicity of xenobiotics and drugs in man is the ultimate question.
Personal View
Authors: Goulding R. 
Published: December 2008

1 Following the establishment, in the USA, of the first poisons information centre, in 1953, the movement has grown globally. Originally, such a service was intended to meet an emergency need. Its efficacy has still not been objectively audited. 2 The suggestion now is that clinical toxicology has become such a diverse subject within the community that simply answering emergency calls over the telephone is not enough. Instead, expertly staffed clinical toxicology units should be set up to cater for much wider problems.
Pharmacodynamic Interactions Between Infused Adenosine and Oral Theophylline
Authors: Minton Neil A. , Henry John A. 
Published: December 2008

1 Five healthy human subjects were given, in single-blind fashion, either (a) 625 mg theophylline orally, followed 4 h later, by a 40 min infusion of adenosine (40 μg kg -1 min-1 for 5 min, 60 μg kg-1 min -1 for 5 min and 80 μg kg-1 min-1 for 30 min), or (b) 625 mg theophylline orally followed by 0.9% sodium chloride infusion, or (c) placebo theophylline tablets followed by adenosine infusion. 2 All five subjects experienced adverse effects during adenosine infusion, mainly at the higher infusion rates; two subjects also experienced chest pain but not during combined treatment with theophylline and adenosine. 3 Diastolic blood pressure (DBP) rose by 16.5 mmHg ( P < 0.001) following treatment with theophylline only, fell by 24.5 mmHg ( P < 0.001) during the adenosine infusion after placebo theophylline and remained unchanged during the adenosine infusion following theophylline. Pulse rate rose by 12 min -1 ( P < 0.01) during adenosine infusion following placebo, but not after theophylline alone or theophylline and adenosine combined. 4 The respiratory rate fell by 6 min-1 ( P < 0.01) during treatment with adenosine only, being lower than for the two treatments containing theophylline ( P < 0.05). 5 Plasma potassium and magnesium fell by 0.25 mmol I-1 ( P < 0.001) and 0.037 mmol I-1 ( P < 0.05), respectively, during treatment with theophylline only, but these effects were not altered by infusion of adenosine. 6 This study has demonstrated interactions between theophylline and adenosine on diastolic blood pressure and respiratory rate, but no interaction on metabolic parameters. Adenosine infusion is unlikely to be of value in the management of theophylline toxicity, but its effects on theophylline-induced cardiac arrhythmias remain unexplored.
Acute Ethanol Administration Reduces the Antidote Effect of N-Acetylcysteine after Acetaminophen Overdose in Mice
Authors: Dalhoff Kim , Hansen Per Boye , Ott Peter , Loft Steffen , Poulsen Henrik E. 
Published: December 2008

1 The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated.2 Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine + ethanol i.p. (same doses as given individually) or saline i.p. (0.4 ml). Survival rates were determined after 24, 48, 72 and 96 h.3 In the N-acetylcysteine group the survival rate was 85%. This rate was significantly reduced to 43% in the N-acetylcysteine + ethanol group (P = 0.0001). In the groups given ethanol or saline alone only 7% and 3%, respectively, survived 96 h.4 The data suggest that the protective effect of N-acetylcysteine on acetaminophen-induced toxicity in fed mice is reduced by concomitant administration of ethanol. This may explain the clinical observation that ingestion of ethanol worsens the prognosis after acetaminophen intoxication.
The Effect of Chronic Alcohol Intake on Prognosis and Outcome in Paracetamol Overdose
Authors: Bray Gary P. , Mowat Craig , Muir Douglas F. , Tredger J. Michael , Williams Roger 
Published: December 2008

1 In a retrospective study, we stratified 79 patients with paracetamol hepatotoxicity into two groups according to weekly alcohol consumption below ( n = 49) or above ( n = 30) Royal College of Physicians' guidelines of 21 units week -1 for males and 14 for females. 2 Survival was lower (33%) and serum creatinine on admission higher (median 207 μmol) in patients whose alcohol consumption was above recommended guidelines than in those whose drank less than this (65.9% and 138 μmol, P < 0.01 and P = 0.027, respectively). An arterial blood pH < 7.30 on admission was also more common in those patients with a higher alcohol consumption (30% v 12.2%, P = 0.05). 3 In all patients whose alcohol consumption exceeded the guidelines, paracetamol overdose was fatal if associated with a serum creatinine greater than 300 μmol in conjunction with a prothrombin time over 100 s and grade 3 or 4 encephalopathy or a peak prothrombin time over 180 s. 4 Chronic alcohol intake above suggested limits is an adverse prognostic feature in cases of severe paracetamol overdose. This effect is partly related to increased nephrotoxicity.
1H-NMR Spectroscopy as a Means of Monitoring Nephrotoxicity as Exemplified by Studies with Cephaloridine
Authors: Murgatroyd L.B. , Pickford R.J. , Smith I.K. , Wilson I.D. , Middleton B.J. 
Published: December 2008

1 Male albino rats were dosed intravenously with either 0.9% saline or cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2 Urine analysis on day 3, after two doses of cephaloridine showed dose-related increases in glucose, total protein, N-acetyl β-D-glucosaminidase, y-glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR spectroscopy showed corresponding disturbed profiles of products of intermediary metabolism indicative of a disruption of renal function. 3 By day 6, after five doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed that all indices had returned to normal. 1H-NMR was demonstrated to provide useful complementary information to conventional techniques on the time course of the onset of the nephrotoxicity and the recovery phase, and was at least as sensitive as conventional urine analysis.
The Immunotoxicity of Tributyltin Oxide (TBTO) does not Increase the Susceptibility of Rats to Experimental Respiratory Infection
Authors: Carthew P. , Edwards R.E. , Dorman B.M. 
Published: December 2008

1 The dietary exposure of rats to tributyltin oxide at a concentration of 150 ppm for 6 weeks is known to lead to a significant reduction in relative thymic weight. 2 To determine whether this reduction in thymic weight also leads to an impairment of function sufficient to alter the host response to micro-organisms, we have examined the development of virus- and mycoplasma-induced pneumonia in TBTO-exposed rats. 3 Using a quantitative histopathological method for measuring both the extent and duration of lung lesions in TBTO-exposed rats, no statistically significant increase in the extent or persistence of virus-induced lung lesions was found in rats exposed chronically to TBTO. 4 The susceptibility of rats to Mycoplasma pulmonis infection, alone, or in conjunction with viral pneumonia, was also not increased by dietary exposure to TBTO.
Prevention of Chloroquine Absorption by Activated Charcoal
Authors: Neuvonen P.J. , Kivistö K.T. , Laine K. , Pyykkö K. 
Published: December 2008

1 The ability of activated charcoal to prevent the absorption of chloroquine was investigated in healthy volunteers, and the effect of the charcoal-chloroquine ratio on the completeness of binding was studied in vitro. 2 After an overnight fast, six subjects ingested 500 mg of chloroquine phosphate with water, and another group of six subjects ingested 25 g of charcoal suspension within 5 min of chloroquine intake. The concentrations of chloroquine in plasma and whole blood were measured by high-performance liquid chromatography for 192 h. 3 Activated charcoal reduced the areas under the plasma and whole blood chloroquine concentration-time curves (AUC) from 0 to 192 h, the total AUCs, and the peak concentrations by 99% (P < 0.001). 4 Chloroquine was very effectively bound by activated charcoal in vitro, even at low charcoal-chloroquine ratios. For example, at a ratio of 5:1, about 98% of chloroquine was bound. 5 Activated charcoal should be very effective in reducing the absorption of that fraction of chloroquine dose which is in the stomach at the time of charcoal administration. Because the acute toxicity of chloroquine is extremely high and death usually occurs within 1-3 h of overdosage, charcoal should be given as early as possible in suspected chloroquine intoxication.
Differences in the Radiotoxicity of Two Plutonium Isotopes in Cells In Vitro: Can they be Ascribed to Different Handling by the Cells?
Authors: Boxler Carmen , Rau Waltraud , Planas-Bohne Felicitas 
Published: December 2008

Exposure of Co631 cells to plutonium leads to increasing cell death depending on the dose and incubation time. The effects, however, are more pronounced with 239Pu, than with 238Pu. Uptake and binding of the two radionuclides during a 5-h incubation are about equal, but 238Pu is lost more rapidly from the cell. There are also differences in the subcellular distribution which lead to a pronounced difference in the distribution of radioactivity. The influence of these differences in the handling of 238Pu and 239Pu by the cell and of the mass difference on the radiotoxicity of the radionuclides is discussed.
Acute Toxicity in Rats of Chlorinated Hydrocarbons Given via the Intratracheal Route
Authors: McCarty Leslie P. , Flannagan Donal C. , Randall Scot A. , Johnson Keith A. 
Published: December 2008

1 The approximate lethal dose (ALD) of six chlorinated hydrocarbons via the intratracheal route has been determined in rats and compared with published oral LD50 values. 2 The compounds tested in this study were dichloromethane, perchloroethylene, trichloroethylene, carbon tetrachloride, chloroform and ethylene dichloride. 3 A method of administering the materials intratracheally to unanaesthetized animals was developed. 4 The intratracheal ALD of the chlorinated hydrocarbons ranged from 3.1 to 17.5% of the oral LD 50 and death was peracute. 5 Aspiration of chlorinated hydrocarbons may present more of a hazard than oral toxicity and should be considered when rendering first aid or emergency medical treatment.
Effects of Concentration Reduction and Partial Replacement of Paraquat by Diquat on Human Toxicity: A Clinical Survey
Authors: Yoshioka T. , Sugimoto T. , Kinoshita N. , Shimazu T. , Hiraide A. , Kuwagata Y. 
Published: December 2008

Paraquat poisoning was studied in 174 patients over a 12-month period when a new, low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v diquat ion; 6 3 cases) replaced the original high concentration paraquat product (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the patients died from circulatory failure accompanied by multiple organ failure within a week of ingesting the products. However, a remarkable reduction in late deaths from respiratory failure was noted in the new product group (17.1% vs 6.3%). This was reflected in this group's improved survival (23.4% vs 34.9%). The improvement in survival seems to be attributable to the dilution of paraquat with diquat which seems to have a different toxicological profile to paraquat.
Sex Hormones and Epididymal Sperm Parameters in Rats Following Sub-chronic Treatment with Hexavalent Chromium
Authors: Ernst Erik , Bonde Jens Peter 
Published: December 2008

Testicular atrophy and reduced epididymal sperm count are known to occur after i.p. administration of high doses of hexavalent chromium to rats. The effect of 0.5 mg kg -1 hexavalent chromium injected i.p. 5 d a week for 8 weeks was investigated in male Wistar rats. A significant reduction in epididymal sperm motility was found at the end of the exposure period. The reduction was reversed after an unexposed period of a further 8 weeks. In addition, a decrease in serum testosterone and an increase in FSH were found at the end of the exposure period. The results indicate that a number of mechanisms may be involved in the deleterious effects of chromate on male fecundity.
Subacute Toxicity of Pentavalent Antimony Compounds in Rats
Authors: AlKhawajah A. , Larbi E.B. , Jain S. , Al-Gindan Y. , Abahussain A. 
Published: December 2008

A subacute toxicity study of pentavalent antimony (Sb) compounds, sodium stibogluconate (SSG) and meglumine antimoniate (MA) was carried out in rats. Three groups of 10 rats each were treated with saline (control group), 300 mg Sb kg-1 d-1 or 900 mg Sb kg-1 d-1 of SSG for 30 d. A parallel study of similar type was conducted for MA. Compared with controls, drug-treated rats showed an impairment of feeding habits and retardation of weight gain ( P < 0.01) during the treatment period. In both SSG- and MA-treated rats there was a dose-related reduction in haemoglobin concentration ( P < 0.001), and hematocrit ( P < 0.001). Red cell count was reduced in SSG-treated rats only. Both drugs, however, significantly raised the white cell count ( P < 0.05). These changes were more pronounced with SSG them with MA. There was no change in MCV, MCH and MCHC. SSG, 900 mg Sb kg-1 d-1, significantly raised AST ( P < 0.005), ALT ( P < 0.01) and alkaline phosphatase activity (P < 0.01). SSG-treated rats also had raised BUN ( P < 0.01) and creatinine ( P < 0.001), but no significant change in bilirubin levels. MA significantly raised AST ( P < 0.01), ALT ( P < 0.01), BUN ( P < 0.001) and serum creatinine levels (P < 0.001), but had no appreciable effect on bilirubin and alkaline phosphatase levels. Both SSG and MA decreased blood glucose levels ( P < 0.01) and induced proteinuria. It is concluded that the pentavalent antimony compounds (SSG and MA) retard growth rate and cause hepatotoxicity, nephrotoxicity and haematological abnormalities. The range and severity of toxicity, however, vary with the preparation and the dose.
Arsenic-Copper Interaction in the Kidney of the Rat
Authors: Schmolke G. , Elsenhans B. , Ehtechami C. , Forth W. 
Published: December 2008

1 The interaction between As and three toxic metals (Cd, Ni and Pb) and Cu (an essential trace metal) in the kidney was investigated in the rat by feeding diets containing various concentrations of As whilst maintaining constant concentrations of the other elements.After 1, 3, 7 and 15 weeks of feeding, metal contents in the renal cortex and medulla, red blood cells and plasma were determined by atomic emission spectrometry (ICP-AES). 2 As accumulated in the whole kidney, whereas Cu accumulated only in the cortex. Accumulation of Cu was found to depend on the feeding period and dietary As concentration.3 As was also accumulated in red blood cells, where saturation was found at 550 μg As g-1cells.4 Although Cd was also accumulated in the cortex, its accumulation was independent of the dietary As concentration. Ni and Pb were not detected by ICP-AES.5 Chromatography of the supernatants from cortical homogenates of control and As-treated rat kidney suggested that Cu accumulated in renal metallothionein (MT). Its accumulation in this fraction was independent of that of Cd, indicating that the As-Cu interaction was not a result of MT induction, but rather that it might result from altered renal handling of Cu with subsequent incorporation into MT.
Chronic Exposure to n-Hexane Induces Changes in Nerve-Specific Marker Proteins in the Distal Peripheral Nerve of the Rat
Authors: Jian Huang  , Shibata Eiji , Kato Kanefusa , Asaeda Nobuyuki , Takeuchi Yasuhiro 
Published: December 2008

1 After long-term n-hexane exposure (2000 ppm, 12 h d-1, 6 d week-1, for 24 weeks), the content of neuron-specific enolase (gamma-enolase), creatine kinase-B and beta-S100 protein in the cortex, cerebellum, spinal cord and proximal and distal sciatic nerves of rats was determined by enzyme immunoassay. 2 The amounts of the three proteins decreased significantly in the distal segment of sciatic nerve, whereas they remained unchanged in the brain and proximal sciatic nerve. The quantitative decline in these marker proteins in the distal sciatic nerve could be related to neurophysiological deficits in the peripheral nerves. 3 This study indicates that the biochemical changes observed are consistent with the clinical and pathological findings of n-hexane neuropathy. These nerve-specific marker proteins can be used to assess solvent-related peripheral neurotoxicity.
Aspects of Orthodox Medicines (Therapeutic Drugs) Poisoning in Urban Zimbabwe
Authors: Nhachi C.F.B. , Habane T. , Satumba P. , Kasilo O.M.J. 
Published: December 2008

1 A retrospective study (extending over 10 years, 1980 to 1989 inclusively) of hospital admission cases, due to therapeutic drug poisoning was carried out at the six main hospitals of Zimbabwe's four cities. 2 The four cities have a total population of approximately 4 million. 3 A total of 1061 cases were recorded and analysed. This constituted 16.7% of all poisoning admission cases (i.e. the fourth biggest cause of poisoning after traditional medicines, household chemicals and snake/insect venom). 4 Of the 1061 cases, 31 % were aged 21-30 years, 21.9% were aged 11-20 years, 14.9% were aged under 5 years and 12.8% were aged 31-40 years. Those aged over 80 years accounted for only 0.6% of the cases. 5 The major groups of drugs implicated were: the analgesics, 22% of the total; sedatives and hypnotics, 13.2%; antipsychotics, 11.6%; antimalarials, 9.3%; antidepressants, 9.0%; antimicrobials, 7.5%; and alcohol, 7.1 %. The other drugs each accounted for the less than 7%; the least used group were the gastrointestinal drugs which formed only 0.6% of the total. Poisoning due to drug abuse was cited at 1.3%. Overdose, either accidental or in the course of treatment, accounted for 63.5% of the cases. 6 The mortality rate was 3.9% and most of the deaths were suicides. 7 Treatment consisted mainly of the administration of ipecacuanha in those under 5 years old age and supportive therapy in adults. A few cases were given an antidote if it was specifically indicated.
Failure of Oral Activated Charcoal to Accelerate the Elimination of Amiodarone and Chloroquine
Authors: Laine Kari , Kivistö Kari T. , Neuvonen Pertti J. 
Published: December 2008

1 The effect of activated charcoal on the elimination of amiodarone and chloroquine was studied in the rat. 2 The study consisted of two separate experiments. Amiodarone and chloroquine were injected subcutaneously at doses of 200 mg kg-1 and 100 mg kg-1, respectively. Six rats in both experiments were put on a charcoal-containing diet 48 h after drug administration, while the control groups remained on a normal diet. 3 Treatment with repeated oral activated charcoal had no effect on the true elimination of amiodarone and chloroquine. 4 These results suggest that, after the distribution of amiodarone and chloroquine into peripheral compartments, their rate of elimination cannot be significantly accelerated with multiple oral doses of activated charcoal.
Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases
Authors: Rochdi M. , Sabouraud A. , Baud F.J. , Bismuth C. , Scherrmann J.M. 
Published: December 2008

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases.Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups.2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1.3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g-1); it was also found in the brain (125 ng g-1).4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.
Intrapleural Administration of Fibres Induces Mesothelioma in Rats in the same Relative Order of Hazard as Occurs in Man after Exposure
Authors: Carthew P. , Hill R.J. , Edwards R.E. , Lee P.N. 
Published: December 2008

1 The dose—response data for the induction of mesothelioma, in rats, by the intrapleural administration of the fibrous zeolite, erionite, has been compared to the published data for the crocidolite and chrysotile forms of asbestos. Erionite is more than two orders of magnitude more carcinogenic than either of the two forms of asbestos examined. 2 The relative sensitivity of the intrapleural and intraperitoneal routes of injection were also examined. The sensitivity of the intraperitoneal over the intrapleural route of administration was considerably greater for all the forms of asbestos examined but not for erionite. 3 The relationship for different fibres, between the number of fibres required to give animals mesothelioma, at the 50% or 10% observable tumour effect level (OTEL) was examined, and a ranking of relative carcinogenicity was made. 4 This showed that the data derived from the dose responses obtained by the intrapleural administration of fibres to rats ranked the relative carcinogenicity of erionite, crocidolite and chrysotile in accord with the known clinical mesothelioma induction in man after exposure to these fibres. Examination of the carcinogenicity ranking from data derived from intraperitoneal injections of fibres was not in accord with the known clinical mesothelioma induction in man for the various asbestos types examined.