bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine and Dobutamine Reduce Myocardial d-Propoxyphene Content in Experimentally Intoxicated Rats
Authors: Pedersen C.B. , Strøm J. , Angelo H.R. , Munksgaard A. , Høgskilde S. , Bredgaard Sørensen M.
Published: December 2008

The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats.

The d-propoxyphene (19 mg kg-1 h-1) was continously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 ?g kg-1 min-1 or 25 ?g kg-1 min-1), dobutamine (25 ?g kg-1 min-1 or 45 ?g kg-1min-1) or normal saline (control). Each group consisted of eight rats.

The myocardial d-propoxyphene content was significantly lower in the two groups given dopamine and in the group given dobutamine 45 ?g kg-1 min-1 than in the control group (P < 0.05).

This finding indicates the benefit of early sympathomimetic intervention with either dopamine or dobutamine in d-propoxyphene intoxication.
Delayed Calcium Channel Blockade with Diltiazem Reduces Paracetamol Hepatotoxicity in Mice
Authors: Deakin Charles D. , Gove Christopher D. , Fagan Elizabeth A. , Tredger J. Michael , Williams Roger
Published: December 2008

1 Diltiazem (30 mg kg-1body weight, intraperitoneally) given to mice 9 h after paracetamol (450 mg kg-1, orally) reduced liver damage, as judged by plasma aspartate aminotransferase activity (median 186, range 6-602 IU I-1, n = 18 vs 466, range 23-3872 IU I-1in 18 saline-treated controls; P < 0.05) with comparable reductions in mortality (14% vs 33%, respectively; NS).

2 Regenerative activity, as judged by mitotic figures in tissue removed at 30 h after paracetamol, was significantly higher in mice treated at 9 h with diltiazem (median 0.83 per high power field vs 0.1 in saline-treated controls; P < 0.05).

3 Diltiazem administered earlier or later than 9 h showed reduced efficacy and in some cases potentiated toxicity, as did nifedipine (40 mg kg-1in divided doses up to 9 h).
Radiation Detriment: Its Quantification and Use in Setting Standards
Authors: Clarke R.H.
Published: December 2008

At the end of 1990 the International Commission on Radiological Protection adopted new recommendations for the control of exposure to ionizing radiation. The main reasons for the revision of existing standards were first, the new estimates of the risks associated with exposure and second, the need to develop a conceptual framework that covered not only occupational exposures but also radon in homes and the consequences of accidents.

This paper addresses these issues and shows how the definition of radiation detriment is used to set new standards in a System of Radiological Protection.
Occupational Mercury Vapour Exposure and Testicular, Pituitary and Thyroid Endocrine Function
Authors: McGregor A.J. , Mason H.J.
Published: December 2008

We have investigated the pituitary-testicular axis in a well-characterized population which was occupationally exposed to mercury vapour. Thyroid stimulating hormone and prolactin were also measured as indices of thyroid and pituitary endocrine function. We found no relation between blood or urine mercury levels or length of occupational exposure with any measurement of endocrine function.

A small, but statistically significant negative correlation between serum sex-hormone binding globulin and the duration of occupational exposure to mercury was found. The physiological significance of this result is unclear.
Complete Heart Block after Flumazenil
Authors: Herd Barbara , Clarke Fiona
Published: December 2008

Flumazenil is a competitive benzodiazepine antagonist. It is indicated for reversal of excess benzodiazepine sedation under certain circumstances, including the reversal of overdosage effects when it is felt best to avoid ventilation, such as in the very old or the very young. We report a case where the use of flumazenil was associated with complete heart block in an elderly patient.
Failure of a 21-Aminosteroid Antioxidant to Ameliorate Cisplatin-Induced Nephrotoxicity
Authors: Holding J.D. , Stell P.M. , Lindup W.E.
Published: December 2008

1 Lazaroid (U74500A), a 21-aminosteroid antioxidant, was administered to rats at a dose of 10 mg kg-1 in an attempt to reduce the toxicity of cisplatin (5 mg kg -1).

2 No protective effect was apparent under the schedule used and, in contrast to other antioxidants and free-radical scavengers, U74500A offers no potential benefit in cisplatin treatment.
Distribution and Elimination of [2-14C]Amino-3, 8-Dimethylimidazo [4, 5-f] quinoxaline in Mice. Analysis by Whole Animal Autoradiography
Authors: Gooderham N.J. , Soames A. , Rice J.C. , Boobis A.R. , Davies D.S.
Published: December 2008

1 2-Amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) is a potent bacterial pro-mutagen and carcinogen, formed when beef is cooked. In mammals, MeIQx is metabolized and activated by liver enzymes, but induces tumours in both hepatic and extrahepatic tissues.

2 Intravenous administration of [14C]MeIQx and whole animal autoradiography has been employed to examine the diposition of MeIQx. Within 10 min, radiolabel was distributed throughout body tissue. Liver levels of radioactivity rapidly rose and remained elevated in comparison to other tissues, throughout the period of study (4 d).

3 At early time points radioactivity accumulated in the stomach, kidney and salivary glands then later in the intestine. Radioactivity was rapidly eliminated from the majority of tissues although did persist in liver and intestines throughout the duration of the study, probably due to covalently bound material. No radioactivity could be detected in the central nervous system, thus neither MeIQx nor its metabolites cross the blood—brain barrier to any significant extent.

4 The rapid elimination of radioactivity from the tissues is in good agreement with the time course of excretion of MeIQx. Irrespective of the route of administration (i.v., i.p., p.o.), a substantial proportion of the labelled material is excreted within 24 h and is present in both urine and faeces in similar quantities.

5 Thus MeIQx is extensively bioavailable, is distributed throughout body tissue and, although the majority is quickly cleared, some remains bound to liver and intestine.
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.
Saturnism Caused by Hand-made Plates: Partial Diagnosis by a Computer-aided Program
Authors: Chassaing B. , Bonini M. , Counord J. , Courtes C. , Nguyen C. , Creppy E.E.
Published: December 2008

A man, aged 41 years, suffering from anaemia and abdominal pains was admitted to the Department of Medicine. Over the previous 2 years he had had several periods in hospital for these symptoms. There was, apparently, no occupational or accidental exposure to toxic substances and a correct diagnosis of the condition had not been possible. The computer-aided program AIDEDIAG II was therefore used to attempt a diagnosis. This approach indicated possible saturnism which was confirmed by metabolic and lead analyses. The lead source was identified as the hand-made food-plates used by the patient for his meals.
Symptomatic Bradycardia Caused by Mianserin at Therapeutic Doses
Authors: Carcone Bernard , Vial Thierry , Chaillet Nicolas , Descotes Jacques
Published: December 2008

An acute episode of symptomatic sinus bradycardia, occurred in a 50-year-old female patient after she had been given a single therapeutic dose of mianserin. Heart rate was corrected by atropine injection. Re-administration of mianserin resulted in the recurrence of bradycardia. Further examination showed no cardiac abnormalities. This case is the first report of conduction defect in a patient given therapeutic doses of mianserin.
Rectal Ulcer with Massive Haemorrhage due to Activated Charcoal Treatment in Oral Organophosphate Poisoning
Authors: Mizutani Taro , Naito Hiroshi , Oohashi Noriyoshi
Published: December 2008

A 42-year-old woman who had ingested a large amount of fenitrothion emulsion was admitted and treated. Treatments consisted of mechanical ventilation, intravenous administration of atropine and pralidoxime and repeated injection of activated charcoal with magnesium sulphate via a nasogastric tube. The patient developed massive rectal bleeding just after she had passed several hard masses of charcoal on the 10th day. Surgical haemostasis of the rectal ulcer was needed to control the haemorrhage.
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.
Effects of Joint Exposures to Selected Peroxisome Proliferators on Hepatic Acyl-CoA Oxidase Activity in Male B6C3F1 Mice
Authors: Ochs J.B. , Baldwin L.A. , Leonard D.A. , Calabrese E.J.
Published: December 2008

The interaction potential of peroxisome proliferators of similar and dissimilar structure was examined in B6C3F1 mice. Mice were fed diets containing varying concentrations of ciprofibrate (Cipro), clofibrate (Clof) or di(2-ethylhexyl)phthalate (DEHP), or combinations of Cipro and Clof or Cipro and DEHP for 4 d. Induction of peroxisomal beta-oxidation, measured by increased acyl-CoA oxidase activity, was used as the endpoint for analysis. An additive response occurred following joint exposure to the structurally related compounds Cipro and Clof, whereas a possible synergistic response occurred at low dose combinations of the structurally dissimilar Cipro and DEHP. These findings represent the first report assessing the in-vivo interaction potential of structurally similar and dissimilar peroxisome proliferators and provides insight into the dose-response nature of joint exposures to certain non-genotoxic carcinogens.
Effect of Lead on the Blood Serum, Liver and Brain Sialoglycoconjugate Levels in Rats
Authors: Patel A.B. , Venkatakrishna-Bhatt H.
Published: December 2008

Rats were exposed to an acute dose of lead (Pb) to study the effect of Pb intoxication on different sialoglycoconjugates in serum, brain and liver. Serum levels of total sialic acid (TSA), perchloric acid (PCA)-soluble sialic acid (PSA), lipid-bound sialic acid (LBSA), free sialic acid (FSA) and α1-acid glycoprotein (α1-AG) were determined. They were also estimated in brain and liver tissues, except for LBSA and FSA. All these constituents were found to be significantly raised in the serum but not in the brain. In the case of the liver, only α1-AG levels were found to be increased significantly, the rest were not altered. The levels of these sialoglycoconjugates in serum might be useful as biomarkers of heavy metal toxicity.
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.
Alcohol in Cerebrospinal Fluid (CSF) and Alcoholism
Authors: Agapejev S. , Vassilieff I. , Curi P.R.
Published: December 2008

Alcohol levels were measured in 15 cerebrospinal fluid (CSF) samples and 14 blood samples from grade III and IV male alcoholic patients with signs of nervous system involvement, and compared with levels detected in 11 CSF samples and 11 blood samples from abstemious patients or patients with grade I or II alcoholism whose CSF had been found to be normal by routine analysis (controls). Among the alcoholic patients, alcohol levels were lower in the CSF than in blood, whereas the opposite was true for the controls. The possible mechanisms underlying this difference are discussed and the need for further study of this topic is emphasized.
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.
Sulphur Derivative of Hexachlorobenzene in Human Urine
Authors: To-Figueras J. , Gómez-Catalán J. , Rodamilans M. , Corbella J.
Published: December 2008

Pentachlorothiophenol, a sulphur derivative of the widespread environmental pollutant hexachlorobenzene (HCB) has been detected and quantified in the urine of a human general population with high body burden of HCB. The sulphur derivative was analysed by GLC-MS as pentachlorothioanisole (PCTA) after hydrolysis and methylation of the respective conjugate and was found in 100% of the samples ( n = 40) with a mean concentration of 1.85 ± 0.98 ng ml-1 (X ± s.d., range 0.58-4.50 ng ml-1). No correlation with urinary pentachlorophenol (PCP) and no sex-related differences were found. The derivative may originate from the biotransformation of HCB stored in tissues and may be a useful maker of HCB metabolism in humans.
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.
Respiratory Symptoms and Ventilatory Capacity in Metal Polishers
Authors: Rastogi S.K. , Gupta B.N. , Husain Tanveer , Mathur N. , Pangtey B.S. , Garg N.
Published: December 2008

To evaluate the long-term effects of metal dusts on the bronchopulmonary system and the synergistic effect of cigarette smoke, a comparative study of spirometric measurements in 104 polishers and 90 unexposed controls was carried out in 25 brass and steelware polishing industries at Moradabad in northern India. The two groups were comparable in terms of age, height, smoking habit and socio-economic status. A total of 58.6% of the polishers had one or more respiratory symptoms, compared to only 25.5% of the controls (P<0.05). Chronic cough was present in 21 polishers (20.2%) as compared to 11.1% of the controls. However, this difference was insignificant. Chronic phlegm was nearly three times as frequent among the polishers as among the controls (17.5% vs 4.4%) (P<0.005). The prevalence of dyspnoea of varying grades was also significantly higher (16.3% as opposed to 4.4%) among the exposed groups. Chronic bronchitis (6.7%) and occupational asthma (4.8%) were found to be confined to polishers. The polishers also experienced acute respiratory symptoms during the work shift. The prevalence of acute respiratory symptoms was recorded for cough in 19 workers (44.1%) followed by dyspnoea in 14 workers (32.5%) and throat irritation in 11 workers (25.5%). Comparison of the mean values of pulmonary function parameters in the polishers and the controls showed significant differences in the smoking and non-smoking groups (P<0.001 ). The polishers exhibited significantly greater acute reductions in various lung functions over the work shift, particularly for forced expiratory flow over the 25-75% portion of the spirogram (FEF25_75%) FEF25% and FEF 50%, than did the controls. Among the exposed group, the acute changes in lung function were found to be significantly larger in the smoking than in the non-smoking polishers. The duration of exposure showed a direct correlation with the acute fall in lung function. Polishers who were exposed to dusts of various metals for more than 10 years showed a significantly greater acute reduction in all the pulmonary functions (P<0.001) thereby indicating that occupational exposure to multimetals in the work environment of the polishing industry had deleterious respiratory effects.
Pesticide-Related Incidents Treated in Finnish Hospitals - A Review of Cases Registered Over a 5-Year Period
Authors: Lamminpää A. , Riihimäki V.
Published: December 2008

Pesticide-related incidents are uncommon in Finland. They comprised 0.11% of all hospitalizations due to poisoning in 1987-88. A search of the nationwide Hospital Discharge Register revealed 78 pesticide-related incidents in a 5-year period. Some 30 different agents were involved, the most frequent being organophosphate and MCPA. Only 36 cases (46%) were judged to be unequivocal or probable pesticide poisonings; 26 (33%) were probably other illnesses because of no or minimal exposure and of the children admitted for follow-up, nine (12%) had potentially marked exposure, but no poisoning developed owing to vigorous early treatment which limited absorption, and seven (9%) cases remained undetermined. According to our analysis, the management of patients with (suspected) pesticide poisoning at hospitals could be further improved if the following procedures were emphasised: decontamination of the skin when appropriate, systematic early estimation of the likely dose involved, analytical verification of pesticide absorption whenever feasible, and consistent collaboration with a toxicological advisory service.
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.
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.
Difenacoum Poisoning as a cause of Haematuria
Authors: Butchery Graham P. , Shearer Martin J. , MacNicoll Alan D. , Kelly Michael J. , Ind Philip W.
Published: December 2008

A man presented with frank haematuria and a grossly prolonged prothrombin time. He was later found to have taken an overdose of difenacoum — a 'superwarfarin' rodenticide. The diagnosis was confirmed by a serum concentration of difenacoum of 0.6 μg ml-1. Overdosage with superwarfarins is discussed and the need for prolonged treatment with vitamin K1 highlighted.
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.
Embryo-Fetal Development Influenced by Lead Exposure in Iron-Deficient Rats
Authors: Singh C. , Saxena D.K. , Murthy R.C. , Chandra S.V.
Published: December 2008

Lead administered (250, 500, 1000 and 2000 ppm Pb as lead nitrate) through drinking water from the 6th to the 14th day of gestation in iron-deficient rats, resulted in a significantly reduced litter size, reduced fetal weight and a reduced crown-rump length, increased resorption and a higher blood-lead uptake in those groups receiving 1000 and 2000 ppm Pb. These animals also had a higher placental lead uptake. However, the level was the same in both groups. Fetal lead uptake remained the same whether or not 2000 ppm lead was given to an iron-deficient or normal iron groups of mothers. This indicates that iron-deficiency renders female rats more susceptible to inducing embryo- and feto-toxicity when given lead through their drinking water.
Fat, Frail and Dying Young: Survival, Body Weight and Pathology of the Charles River Sprague-Dawley-Derived Rat Prior to and Since the Introduction of the VAFR Variant in 1988
Authors: Nohynek G.J. , Longeart L. , Geffray B. , Provost J.P. , Lodola A.
Published: December 2008

Trends in survival and body weight were evaluated in 2140 control Sprague-Dawley-derived [Crl: COBS-CD(SD)BR and Crl: COBS-VAF CD(SD)BR] rats used for 24-month rat carcinogenicity studies between 1979 and 1991, Body weight and survival were remarkably stable in the CD-COBS rats used during 1979-1987: at 24 months, the mean survival in males was 68± 5%, and 60± 5% in females, With the CD-COBS-VAF rat, a variant of the CD-COBS strain used between 1988 and 1991, the survival at 24 months dropped to 41± 3% in males, and 44± 7% in females compared to the CD-COBS. The CD-COBS-VAF rat had a significantly reduced life span ( P<0.001 at 24 months), a significant increase in mean body weight (males at 6 months : 672± 24 g vs. 536± 6 g; females : 359± 7 g vs 308± 3 g; P<0.001 ) and food consumption (males at 6 months : 31.3± 3.3 vs. 25.4± 2.1 g d-1 ; females: 22,0± 2.7 g v. 20.3± 2.0 g d-1 ; P<0.001). CD-COBS-VAF rats which failed to survive up to study termination had individual body weights at 3, 6 and 12 months which were significantly higher (P<0.001 ) than those which survived until 24 months. Our historical data base of control rats (CD-COBS and CD-COBS-VAF) in carcinogenicity studies revealed a significant (males: P<0.001; females: P<0.01) and inverse linear relation between mean 3-month body weight and 24-month survival. When compared to CD-COBS animals, CD-COBS-VAF rats showed an increase in the incidence of pituitary tumours in males, mammary fibroadenomas in females, an increase in the incidence and severity of glomerulonephrosis, and a greater incidence of animals which died without any obvious pathology. It is concluded that, in our Sprague-Dawley substrains, both the individual and the group mean body weights in early adult life appear predictive for the individual and group life expectancy. The decrease in longevity in the CD-COBS-VAF rat is principally due to disease and degeneration processes associated with fast growth and high body weight.
Toxicokinetics of Dimethylacetamide (DMAc) in Rat Isolated Perfused Liver
Authors: Palmen N.G.M. , Evelo C.T.A. , Borm P.J.A. , Henderson P.Th.
Published: December 2008

Dimethylacetamide (DMAc) is a skin-penetrating solvent able to induce hepatic damage after chronic exposure. Previous research has indicated that metabolism may be saturated at its present TLV/TWA (10 ppm). Biological monitoring of monomethylacetamide (MMAc), the primary metabolite of DMAc, might therefore underestimate exposure to DMAC and related health hazards. We used the recirculating perfusion technique in isolated rat liver to evaluate DMAC metabolism. Medium concentrations starting at about 30, 50, 100 and 275 μM, respectively, were tested. Perfusate samples were taken regularly and analysed for DMAc; pharmacokinetic parameters (extraction ratio and clearance) were calculated for each perfusion. Inlet DMAc concentrations were calculated and concentration groups divided in 16, 36, 70, 160, 225 μM. The extraction ratio of the 16 μm group differed significantly from the other concentration groups tested. DMAc metabolism was saturated at a DMAc concentration of 36 μM. Extraction ratios were unaffected when cimetidine, an inhibitor of cytochrome P450 activity, was added to the perfusion medium or when cimetidine-pretreated animals were used. DMAc clearance was 2.20 ml min-1 at a medium concentration of about 36 μM. Extrapolation of the observed (rat) liver clearance to man showed that airborne concentrations of 18 ppm would, under the presumptions used, lead to saturated metabolism of DMAc; however, saturation at even lower concentrations could not be excluded.