bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Poisoning with the β-Blocker Bisoprolol
Authors: Tracqui A. , Kintz P. , Mangin P. , Lenoir B.
Published: December 2008

A case of bisoprolol self-poisoning resulting in full recovery of the patient is described. The peak plasma level of bisoprolol was 541 ng ml-1. Sinus bradycardia was the only symptom observed, suggesting that cardioselectivity and absence of membrane stabilizing activity contribute to reduce the severity of β-blocker intoxication.
Toxicological Findings after Fatal Amitriptyline Self-Poisoning
Authors: Tracqui A. , Kintz P. , Ritter-Lohner S. , Mangin P. , Lugnier A. , Chaumont A.
Published: December 2008

A case of fatal self-poisoning with amitriptyline is reported. Both the drug and its metabolite nortriptyline were quantified in several post-mortem tissues and fluids, including vitreous humor. Results are discussed in the light of the existing literature.
Anticholinesterase Poisoning in Turkey - Clinical, Laboratory and Radiologic Evaluation of 269 cases
Authors: Adnan Öztürk M. , Kelestimur F. , Kurtoglu S. , Güven K. , Arslan D.
Published: December 2008

A retrospective study was conducted on 269 patients with anticholinesterase poisoning who had been admitted to the Internal Medicine and Pediatric Clinics over the past 10 years. Their ages ranged from 17 d to 62 years. In adults, suicide was the most common means of intoxication. Miosis was the most frequent symptom and was seen in 80.66% of the patients. Hyperglycaemia, hypoglycaemia, hypokalaemia, hyperkalaemia, hyperchloraemia, hypochloraemia and hyponatraemia were among the electrolytic and haematologic disorders (hyperglycaemia 48.00%, hypoglycaemia 6.40%). There were also electrocardiographic abnormalities. Asthma, although usually a late complication, was also noted at the beginning of treatment. Mortality rates were 8.98% for children and 9.6% for adults. Since hypoglycaemia was found in all the patients who died, it was accepted as an ominous prognostic sign. We think that anticholinesterase poisoning is an important health problem in our country. It is much less common in developed than semi-developed countries, and a complete understanding of it is essential for the emergency physician.
Vitamin E and Selenium in Gentamicin Nephrotoxicity
Authors: Ademuyiwa O. , Ngaha E.O. , Ubah F.O.
Published: December 2008

1 The sequence of renal cellular membrane damage induced by gentamicin was studied in the rat by using the release of alkaline phosphatase, acid phosphatase, muramidase and protein from renal cells as indices of renal damage.

2 The protective effect of a combination of vitamin E and selenium against renal damage was also investigated.

3 Gentamicin (60 mg kg -1 body weight) was nephrotoxic within 12 h of the first dose.

4 The plasma membrane of the renal tubules is damaged before the lysosomal membrane is affected.

5 A combination of vitamin E (1 mg g-1 body weight) and selenium (4 × 10-3 mg g-1 body weight) attenuates the renal damage induced by gentamicin. Results suggest synergism between vitamin E and selenium in attenuating the renal damage. The possible mechanism of attenuation is discussed.

6 Vitamin E and selenium may have anti-diuretic potential.
Morphine-6-Glucuronide might Mediate the Prolonged Opioid Effect of Morphine in Acute Renal Failure
Authors: Bodd Egil , Jacobsen Dag , Lund Ellen , Ripel Åse , Mørland Jørg , Wiik-Larsen Else
Published: December 2008

1 A 43-year-old male developed acute kidney failure due to ethylene glycol poisoning. He was treated with bicarbonate to combat metabolic acidosis, ethanol as an antimetabolite and haemodialysis to remove the glycol and its toxic metabolites. He was kept on a respirator and sedated with morphine. Peritoneal dialysis was given for 36 d. Following sedation with morphine for 11 d, the patient was given naloxone and then extubated. The antidote had to be continued for 14 d to prevent respiratory depression, until kidney function improved.

2 Only morphine-6-glucuronide (M-6-G) was found in the plasma and CSF at concentrations which might explain the opioid effects observed in the patient during the days after the cessation of morphine treatment. The ratio of the area under the concentration-time curve (AUC) of morphine-3-glucuronide (M-3-G) to M-6-G was 2:1. The elimination half-lives of M-3-G and M-6-G were 55 and 82 h, respectively. The clearance data indicate that most of the glucuronides were eliminated by peritoneal dialysis during renal failure.

3 The data suggest that M-6-G exerts opioid effects and is retained in acute kidney failure. Morphine should therefore not be used preferentially as a sedative/analgesic in pronounced kidney failure.
Pre-embarkment Prognostication for Acute Paraquat Poisoning
Authors: Yamaguchi Hiroshi , Sato Shigehito , Watanabe Seiji , Naito Hiroshi
Published: December 2008

1 In order to assess which laboratory parameters could be related to the prognosis of patients with acute paraquat poisoning, we reviewed the medical records of 160 patients who had ingested paraquat in an attempt at suicide.

2 Serum creatinine and potassium concentrations, arterial blood bicarbonate and base excess levels, arterial blood pH, volume of paraquat ingested and the strength of the urinary paraquat qualitative test (sodium dithionate colour reaction) on admission in the surviving patients were significantly different from those of the patients who died within 48 h of ingestion.

3 The relationship of the quantity Eq1 defined as:

Eq1 = ([K +] × [HCO-3]) / ([Cre] × 0.088) (mEq l-1 )

against the interval of time after ingestion to admission (T) had a significant correlation with prognosis ( P < 0.01). Patients with Eq1 > (1500 - 399 × LogT) had a 90% survival rate, Eq1: (930 - 399 × LogT) < Eq1 ≤ (1500 - 399 × LogT) 38% and Eq1 ≤ (930 - 399 × LogT) 3%, P < 0.01.
Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review
Authors: Woodward K.N.
Published: December 2008

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element.

2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena.

3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship.

4 More studies are needed on the mechanism of renal cystogenesis.
A Histochemical Study of Changes Observed in the Mouse Diaphragm after Organophosphate Poisoning
Authors: Bright J.E. , Inns R.H. , Tuckwell N.J. , Griffiths G.D. , Marrs T.C.
Published: December 2008

A sublethal dose of sarin (GB, isopropyl methylphosphonofluoridate) was administered to mice. The animals were killed up to 28 d after dosing and frozen sections were made of the excised diaghragms which were stained using haematoxylin and eosin and a modified Gomori trichrome method. Muscle fibre degeneration and mononuclear infiltration were seen, notably at 24 h and 3 d. A number of histochemical procedures were carried out, including the GBHA procedure for ionized calcium. Calcium accumulation, seen at 4 h, was the earliest abnormality observed. All changes were rapidly regressing by 5 d and histological appearances were normal by 14 d. It was concluded that sarin produced myopathic changes preceded by calcium accumulation.
Expression of N-Acetyl Transferase in a Human Monocytic Cell-Line, U937
Authors: Kelly S.L. , Sim E.
Published: December 2008

1 N-acetyl transferase (NAT) catalyses the acetylation of arylamine and hydrazine drugs and other xenobiotics. The activity of one isozyme (polymorphic NAT) varies amongst indiviudals but the other (monomorphic NAT) does not.

2 The human monocytic cell-line U937 transcribes the gene for monomorphic N-acetyl transferase.

3 Although the gene for polymorphic N-acetyl transferase is present in these cells, its expression is not detected.

4 It is concluded that U937 cells are a useful model for studying the metabolism of arylamines and hydrazines by human monomorphic N-acetyl transferase.
Fatal Accidental Inhalation of Bromochlorodifluoromethane (Halon 1211)
Authors: Lerman Yehuda , Winkler Eyal , Tirosh Moshe S. , Danon Yehuda , Almog Shlomo
Published: December 2008

Bromochlorodifluoromethane (Halon 1211) is a widely used fire extinguishing agent. Several cases of sudden death in teenagers associated with BCF abuse have been reported. BCF is used as a fire extinguisher in battle tanks. Two young previously healthy male soldiers were accidentally exposed to BCF in a battle tank. The tank driver died, but the gunner survived the event with no medical complications. It is concluded that BCF should be used in confined chambers only after the evacuation of all personnel.
In-Vitro Adsorption Studies of Isoniazid
Authors: Orisakwe O.E. , Akintonwa A.
Published: December 2008

In-vitro experiments were performed to investigate the extent of adsorption of isoniazid to activated charcoal and locally produced activated carbon black (N220) and to explore the effect of varying pH on this adsorption. The results of the study indicated that activated charcoal and activated carbon black adsorbed isoniazid effectively. Adsorption was dependent upon the quantity of charcoal used. With charcoal quantity at 0.5 g, adsorption was virtually completed within 60 min. The mean or composite adsorption capacity of activated charcoal and activated carbon black (?g ml-1 of charcoal) were 325 and 278, respectively. The result of adsorption isotherms indicated no change in binding capacity of the drug from solutions of different pH.
Quantitation of Albumin and Alpha-1-Acid Glycoprotein in Human Cervical Mucus
Authors: Salas Herrera I.G. , Pearson R.M. , Turner P.
Published: December 2008

1 Concentrations of albumin and alpha-1-acid glycoprotein (AGP) in human cervical mucus have been measured by a radial immunodiffusion technique.

2 The cervical mucus samples were obtained from women on combined oral contraceptives (Group A) and from women not taking this medication (Group B). In group A the mean level of albumin was 75.6 (range 22-198) mg 1-1and for AGP 6.5 (range 3-12) mg 1-1. In group B the mean level of albumin was 72.9 (range 22-148) mg 1-1and for AGP 6.6 (range 3-14) mg 1-1.

3 The levels of albumin and AGP in cervical mucus were less than 1% of the concentration in serum and were not affected by combined oral contraceptives.

4 The clinical and toxicological consequences of these observations, in terms of the disposition of drugs and other chemicals in the female genital tract, await elucidation.
Absence of Polymorphism of Sparteine Oxidation in the South African Venda
Authors: Sommers De K. , Moncrieff J. , Avenant J.C.
Published: December 2008

1 This study has found no occurrence of poor metabolism of sparteine within a South African Venda populaton of 97 subjects.

2 On the basis of MR (metabolic ratio) the mean and distribution of the results are very similar to those found in Ghanaians.5,14

3 The distribution is also similar to that for fast metabolizers in Caucasians.14

4 It is concluded that different P450 cytochromes are responsible for immediate oxidation of debrisoquine and sparteine, but that both may be activated by the same P450 reductase.
A Pilot Study on the Urinary Excretion of Porphyrins in Human Populations Chronically Exposed to Arsenic in Mexico
Authors: García-Vargas Gonzalo G. , García-Rangel Adalberto , Aguilar-Romo Manuel , García-Salcedo Javier , del Razo Luz Maria , Ostrosky-Wegman Patricia , Cortinas de Nava Cristina , Cebrián Mariano E.
Published: December 2008

1 The aim of this pilot study was to investigate if the porphyrinuria produced by arsenic in rodents was present in humans chronically exposed to arsenic via drinking water.

2 The concentrations of uroporphyrin, coproporphyrin and total arsenic in urine were compared between 21 individuals exposed to arsenic in their drinking water (0.390 mg 1-1) and 19 controls exposed to 0.012 mg 1-1.

3 Arsenic-exposed individuals had significantly higher total arsenic concentrations in their urine than the control group. No increase in urinary porphyrin excretion was found in exposed individuals. However, an inversion of the coproporphyrin/uroporphyrin (COPRO/ URO) ratio was observed in most exposed individuals. This inversion was caused both, by a decrease in coproporphyrin excretion and an increase in uroporphyrin excretion.

4 No demonstrable correlations between porphyrin excretion, the COPRO/URO ratio and total arsenic concentration in urine were found in exposed individuals.
Efficacy of Tiron for Enhancing the Excretion of Uranium from the Rat
Authors: Stradling G.N. , Gray S.A. , Moody J.C. , Ellender M.
Published: December 2008

Tiron (sodium 4, 5-dihydroxybenzene-1,3-disulphonate) has been suggested as a possible antidote for acute uranium poisoning. In this study, the compound has been administered intraperitoneally to rats in dosages of 30, 300 or 1000 μmol kg-1at 20, 60 and 180 min after the intratracheal instillation of uranyl nitrate. The amounts of uranium deposited in the lungs of rats were equivalent to intakes by workers of about 12 times the permitted daily limit of 2.5 mg. The average body content of uranium at 5 d after exposure were, respectively, about 100%, 78% and 65% of those in untreated animals. It is concluded that the administration of Tiron is of limited practical value for treatment of uranium exposures not greatly in excess of the permitted intake.
Poisoning with Oxybutynin
Authors: Banerjee S. , Routledge P.A. , Pugh S. , Smith P.M.
Published: December 2008

A case of poisoning with 100 mg of oxybutynin in a 34-year-old female is reported. The main features were anticholinergic effects, including stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin and retention of urine. She had a sinus tachycardia which resolved 3 h after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 h. She recovered fully on symptomatic treatment alone.
Recovery of Biochemical Changes Induced by 1, 2-Dichloro propane in Rat Liver and Kidney
Authors: Trevisan Andrea , Troso Ornella , Maso Stefano
Published: December 2008

1 Biochemical changes in male, Wistar rats, treated with different doses of 1,2-dichloropropane (50-500 mg kg-1 body weight), were investigated at the end of a 4-week treatment and after a 4-week recovery period.

2 The behaviour of Phase I and Phase II metabolic steps and of the angiotensin converting enzyme activity of the renal proximal tubule brush border were determined.

3 Phase II is more affected by the solvent than Phase I metabolism, and liver metabolism is more affected than the kidney.

4 Angiotensin converting enzyme activity from the proximal tubule brush border appears to be the most sensitive parameter of kidney involvement during treatment.

5 After a 4-week recovery period all the metabolic indices together with angiotensin converting enzyme activity have returned to normal. Only liver reduced glutathione content shows a slight, but significant, increase for the highest dose (500 mg kg -1 body weight).

6 The results show that the biochemical changes induced in liver and kidney by 1,2-dichloropropane are reversible.
Evidence of Soil-Pica Behaviour and Quantification of Soil Ingested
Authors: Calabrese Edward J. , Stanek Edward J. , Gilbert Charles E.
Published: December 2008

A previously published report1 on soil ingestion in children, revealed evidence that one of the subjects, a 3.5-year-old female, displayed soil-pica behaviour. Soil ingestion estimates for this child ranged from approximately 5 to 7 g d -1 for seven of eight soil tracers employed. The present paper revealed that the soil-pica behaviour occurred only in the second of the two weeks of observation, during which daily soil ingestion rates ranged from 10 to 13 g d-1. Tracer recovery studies displayed acceptable precision (i.e. 100% < ± 30%) for six of the eight tracers during the soil-pica episode (week 2). Evaluation of the weekly soil ingestion values of the remaining 63 subjects indicated no convincing evidence of soil-pica behaviour in this group of children aged 1-4.
Risks of Premature Death and Cancer Predicted by Body Weight in Early Adult Life
Authors: Roe F.J.C. , Lee P.N. , Conybeare G. , Tobin G. , Kelly D. , Prentice D. , Matter B.
Published: December 2008

In a study of 30 months duration, involving 600 male and 600 female Wistar rats fed on 12 different diets/dietary regimes, none of which involved deliberate exposure to any known genotoxic carcinogen, highly significant between-group differences were observed in survival and incidence of various neoplastic and non-neoplastic diseases. A full report of the findings is being prepared. Here we report that, irrespective of diet or dietary regime, there were highly significant correlations of body weight at 29 weeks of age with premature death (P < 0.0001 in both males and females), with development of benign or malignant neoplasm of any site ( P < 0.0001 in males and P < 0.01 in females) and with development of malignant neoplasm at any site ( P < 0.0001 for sexes combined). Numerous kinds of neoplasm contributed to these overall correlations. The most significant were pituitary tumour ( P < 0.0001), mammary gland tumour ( P < 0.0001), squamous or anaplastic carcinoma of the jaw ( P < 0.001), and subcutaneous mesodermal tumours ( P < 0.05). The 20% of rats that were heaviest at 29 weeks were more than twice as likely to die prematurely than the lightest 20% (2.56 times - males, and 2.11 times - females), and almost twice as likely to develop a malignant tumour (1.87 times for the sexes combined). These findings have important implications for the design and interpretation of carcinogenicity tests in rodents and of laboratory and human studies of relationships between diet, ageing-related degenerative diseases, and cancer.
Considerations Regarding the Development of Individual Non-clinical Test Strategies in the European Community
Authors: Günzel P. , Bass R.
Published: December 2008

The wish of pharmaceutical companies to be given the most binding possible preclinical test programmes for a new product, and the tendency of authorities to regulate to a great extent the preclinical testing of new drugs (especially at a multinational level), has led to differing requirements and practices in preclinical testing in different areas of the world.

These differing requirements and practices have of necessity brought in their wake varying scientific criteria, with particular regard to animal protection, ethical standards, as well as imposing apparently unjustified extra financial costs. In order to improve this situation, the development of drug-specific preclinical test strategies is proposed in a drafted E. C. Note for Guidance, which incorporates already existing drug-testing guidelines and method recommendations.

This draft Note for Guidance points to general methods of analysing problems and reaching decisions and thus appears to be worthy of recommendation as practical and desirable. It requires the co-operation of drug producers and supervisory authorities at a high scientific and ethical level. With regard to the state-of-the art and the socio-political background, the fulfilment of these requirements would appear not only to be appropriate but also imperative. To put them into practice would contribute enormously to the improvement of drug development and to de-emotionalization of the public debate. Therefore, comments on these draft guidelines from societies and associations are urgently sought and awaited with keen interest.
Chloracne Caused by Ingestion of Olive Oil Contaminated with PCDDs and PCDFs
Authors: Rodriguez-Pichardo A. , Camacho F. , Rappe C. , Hansson M. , Smith A.G. , Greig J.B.
Published: December 2008

1 All members of a Spanish family (father, mother and six children) developed chloracne.

2 The causative agent was found to be the family's stock of olive oil, which had become contaminated with polychlorinated dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), pentachlorophenol, and hexachlorobenzene.

3 The more highly chlorinated PCDDs, in particular octachlorodibenzo- p-dioxin, were the predominant congeners in the oil.

4 Three members of the family exhibited either an overt or a sub-clinical disturbance of kidney function. The father also had a chronic respiratory problem. These changes could not be unequivocally attributed to the PCDDs.

5 Experimental toxicity of the oil was limited to the development of an hepatic porphyria in mice.

6 A serum sample, taken 5 years after consumption of the oil ceased, contained high levels of the PCDDs and PCDFs. Extrapolation back to ingested dose was used to validate dosage estimates.

7 The use of toxicity equivalence factors (TEFs) provided estimates of cumulative dosage to produce chloracne as 0.13-0.31 μg 2378-TCDD kg-1 (using EPA TEFs) or 6.7-16 μg 2378-TCDD kg-1 (using Nordic/NATO TEFs).

8 This is the first incident in which human toxicity is related primarily to ingestion of PCDDs and for which estimates of dosage can be made.
Effect of Activated Charcoal on the Absorption of Amiodarone
Authors: Kivistö Kari T. , Neuvonen Pertti J.
Published: December 2008

1 The ability of activated charcoal to prevent the absorption of amiodarone was studied in 18 healthy volunteers, divided into three groups of six subjects.

2 All subjects were administered a single dose of 400 mg amiodarone; one group ingested the drug with water only (control) and the second with 25 g of activated charcoal as a water suspension. The subjects in the third group were given 25 g of charcoal immediately after the 1.5 h blood sample.

3 The extent of amiodarone absorption was reduced by about 98% by simultaneously administered charcoal ( P < 0.001); taking charcoal 1.5 h after amiodarone still resulted in a 50% reduction in amiodarone bioavailability ( P < 0.05).

4 These results indicate that activated charcoal should be effective in preventing amiodarone absorption in acute poisoning.
Polycyclic Aromatic Hydrocarbons in Traditional Medicinal Preparations
Authors: Jani J.P. , Raiyani C.V. , Mistry J.S. , Kashyap S.K.
Published: December 2008

Ayurvedic medicinal preparations, commonly known as bhasmas, were analysed for the determination of polycyclic aromatic hydrocarbons (PAH). All the preparations contained PAH. The level of total PAH varied widely (2.32-9.55 ppm) among the preparations tested. Similarly, the benzo(a)pyrene level also varied the highest concentration being 9.7 ppm.
Hyperphosphataemia and Hypocalcaemia Induced by Hypertonic Phosphate Enema - An Experimental Study and Review of the Literature
Authors: Grosskopf Itamar , Graff Eran , Charach Gideon , Binyamin Gideon , Spinrad Sara , Blum Ilana
Published: December 2008

1 The study objective was to determine the hyperphosphataemic and hypocalcaemic effect of hypertonic phosphate enema. The study was conducted in a department of Internal Medicine at a University Medical Center.

2 Fourteen patients were studied. Patients' mean age (± s.d.) was 78.5 ± 9 years. The creatinine clearance was 48.2 ± 17.4 ml min-1 (mean ± s.d.).

3 500 ml (approx. 7 ml kg-1) of Fleet enema (FE - Na2HPO4.7H 2O 224 mmol l-1 and NaH2PO4.H 2O 1160 mmol l-1) were administered to each patient. Blood was drawn before FE administration and ½, 1, 3, 5, 12 and 24 h thereafter. Serum was analysed for levels of inorganic phosphorus and for calcium.

4 The serum inorganic phosphorus level rose from 1.01 ± 0.3 mmol l-1 to 1.4 ± 0.5 mmol l-1 ( P = 0.001) 1 h after FE was administered. Serum calcium decreased from 2.32 ± 0.12 mmol l-1 to 2.12 ± 0.1 mmol l-1 ( P < 0.001) 12 h after FE was administered.

5 We conclude that FE carries a potential risk for acutely ill elderly patients. To avoid untoward effects due to hyperphosphataemia and hypocalcaemia, the phosphate load must be adjusted to the patient's renal function, i.e. enema volume is to be lowered when phosphate concentration is high, so that if renal function is compromised the amount of phosphate absorbed does not exceed renal excretion capacity.
Studies of the Pharmacokinetics and Metabolism of 4-Aminopropiophenone (PAPP) in Rats, Dogs and Cynomolgus Monkeys
Authors: Wood S.G. , Fitzpatrick K. , Bright J.E. , Inns R.H. , Marrs T.C.
Published: December 2008

The pharmacokinetics and metabolism of 4-aminopropiophenone (PAPP), a cyanide antidote, have been studied in rats, dogs and cynomolgus monkeys using14C-PAPP. Radiolabelled material was rapidly excreted in all three species, mainly in urine. In rats, PAPP was metabolized by N-acetylation, while in dogs, ring and aliphatic hydroxylation occurred. In monkeys, both N-acetylation and oxidation took place. In the latter pathway, PAPP was oxidized to p-aminobenzoic acid which underwent amino acid-conjugation to p-aminohippuric acid. In rat blood in vitro, the PAPP metabolites, p-aminobenzoic, p-aminohippuric and N-acetyl- p-aminobenzoic acid were only weak methaemoglobin producers.
The Effect of Repeated Oral Doses of Lornoxicam on Antipyrine Elimination in Normal Human Volunteers
Authors: Ravic M. , Johnston A. , Turner P. , Takacs F. , Rosenow D.E.
Published: December 2008

Treatment with lornoxicam 4 mg twice daily for 14 d did not produce any change in salivary antipyrine elimination in 11 of 12 healthy volunteers. Anomalous results in one subject are presented and discussed.
A Comparison of Spongiosis Induced in the Brain by Hexachlorophene, Cuprizone and Triethyl Tin in the Sprague-Dawley Rat
Authors: Purves D.C. , Garrod I.J. , Dayan A.D.
Published: December 2008

The effect of hexachlorophene (HCP; 2,2'-methylenebis (3,4,6-trichlorophenol), cuprizone (CPZ; bicyclohexone oxaldihydrazone) and triethyl tin (TET; triethyl tin sulphate) in producing vacuoles in the brain of the Sprague-Dawley rat has been quantified by image analysis of the extent of the spongy change in the white matter. The state of the astrocytes was assessed by immunocytochemical staining for glial fibrillary acidic protein (GFAP). HCP and TET caused a dose-related spongiosis, but cuprizone had no significant effect on the brain. With chronic HCP treatment, the spongiosis was accompanied by astrocyte hypertrophy and proliferation, and the extent of the gliotic reaction was related to the dose of HCP. The results demonstrate that HCP can produce and maintain astrocyte proliferation in the rat brain. Such an agent was required for use in an investigation of a putative tumour promoter in the rat.
Fatal Cyanide Poisoning from Cassava-Based Meal
Authors: Akintonwa Alade , Tunwashe O.L.
Published: December 2008

Three patients admitted to the Accident and Emergency Unit of Lagos University Teaching Hospital (LUTH) after eating a cassava based meal 'Gari' died shortly after admission. The patients vomited and complained of abdominal pain immediately after the meal. They were unconscious with renal failure and died of cardiopulmonary arrest. The cyanide levels in the blood and urine averaged 1.12 and 0.54 mg 1-1, respectively. Cassava contains cyanogenic glycosides which slowly release cyanide and this may have been responsible for the death of these patients. There is an urgent need to establish maximum tolerable levels of cyanide in 'Gari' and other cassava food products.
Toxicological Findings after Fatal Fenfluramine Self-poisoning
Authors: Kintz P. , Mangin P.
Published: December 2008

A fatal case involving the suicidal ingestion of fenfluramine is presented. The drug was quantified using gas chromatography. The blood concentration of fenfluramine was 7.46 mg 1-1. Chronic use of fenfluramine was clearly demontrated by the presence of drug in hair at 14.1 ng mg-1.
An Acute Mercuric Mercury Poisoning: Chemical Speciation of Hair Mercury Shows a Peak of Inorganic Mercury Value
Authors: Suzuki T. , Hongo T. , Matsuo N. , Imai H. , Nakazawa M. , Abe T. , Yamamura Y. , Yoshida M. , Aoyama H.
Published: December 2008

A woman ingested a dose of sublimate (approximately 0.9 g) in an attempted suicide. She survived and recovered in response to a combination of therapies including chelate (BAL) therapy, plasma exchange, haemodialysis and peritoneal dialysis.

Serum inorganic mercury concentration, urinary inorganic mercury excretion and hair inorganic and organic mercury and selenium concentrations, along the length from the scalp to the distal part, were measured. Longitudinal analysis of hair, revealed a peak in inorganic mercury corresponding to the time of mercury ingestion. Organic mercury and selenium in the hair had different patterns of longitudinal variation from that of inorganic mercury. The biological half-life (23.5 d) of serum inorganic mercury levels was in good agreement with values previously reported in the literature.
Interindividual Variations in Enzymes Controlling Organophosphate Toxicity in Man
Authors: Mutch Elaine , Blain Peter G. , Williams Faith M.
Published: December 2008

1 Interindividual variations in an unexposed population have been defined for five enzymes involved in organophosphate (OP) toxicity. The enzymes measured were: red blood cell acetylcholinesterase (AChE), lymphocyte neuropathy target esterase (NTE), serum cholinesterase (ChE), serum paraoxonase and serum arylesterase.

2 AChE and arylesterase were normally distributed in the population whilst the distribution of NTE, ChE and paraoxonase deviated significantly from normal.

3 Assay precision and intra-individual variability were measured for each of the enzymes; the effect on interindividual variation was assessed.

4 Variations in enzyme activities between individuals could have profound effects on susceptibility to OP toxicity. Prior determination of these enzymes may be predictive of susceptibility.

5 Lymphocyte NTE has some limitations as an indicator of exposure to neurotoxic OPs.
Biochemical and Histological Alterations in Rats after Acute Nitrogen Dioxide Intoxication
Authors: Meulenbelt J. , van Bree L. , Dormans J.A.M.A. , Boink A.B.T.J. , Sangster B.
Published: December 2008

1 In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication.

2 Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology.

3 After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) 1 the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration.

4 The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, β-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the β-glucuronidase activity showed a 10-fold increase.

5 Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity.

6 Repair was almost complete 7 d following exposure.
The Interactive Effect of Chlorine, Copper and Nitrite on Methaemoglobin Formation in Red Blood Cells of Dorset Sheep
Authors: Langlois Cynthia J. , Calabrese Edward J.
Published: December 2008

Simultaneous exposure to chemicals which can oxidize the haemoglobin of the red blood cell to methaemoglobin is common. Although the effects of some of these agents have been documented individually, little research considers the interactive effects. In-vitro experiments on the treated blood of female Dorset sheep assessed the interactive capacity of chlorite, copper and nitrite to affect methaemoglobin formation. All combinations of doses which produced 2.5, 5, 10% methaemoglobin were tested in all possible combinations (a total of 80), as were the controls. This included data on each chemical alone, each two-way combination and the three-way combination. The response is largely additive (the sum of the individual effects) except for one of the two-way interactions, chlorite/nitrite (P < . 01), which showed antagonism. Chlorite may oxidize nitrite which could explain the less-than-additive response. Overall, the result of combining these agents on methaemoglobin was additive.
Long-Term Anticonvulsant Therapy Worsens Outcome in Paracetamol-Induced Fulminant Hepatic Failure
Authors: Bray Gary P. , Harrison Philip M. , O'Grady John G. , Tredger J. Michael , Williams Roger
Published: December 2008

1 Paracetamol hepatotoxicity has been found to be potentiated by anticonvulsant drugs in animal experiments; isolated case reports in humans sugest that long-term anticonvulsant therapy may also adversely influence outcome following overdose.

2 We compared the clinical course, after paracetamol overdose, of 18 patients on long-term anticonvulsant therapy with corresponding features in two published series of paracetamol-induced fulminant hepatic failure from this unit: 297 patients seen between 1973 and 1985 and a further 99 between October 1986 and April 1988.

3 Mortality in those patients who were taking anticonvulsants, but who did not receive N-acetylcysteine, was higher than in either of these series (93.3% vs 64.6% and vs 57.9%, P< 0.025). Although not statistically significant, there were also trends towards more severe coma (grade 3 or 4: 93.3% vs 75.4%, 1986-88), acidosis (pH less than 7.30: 40% vs 22.6%, 1973-85) and coagulopathy (prothrombin time greater than 100 s: 53.3% vs 33.7%, 1973-85). In the small number of patients given N-acetylcysteine, mortality was similar to that in the 1986-88 series (1/3 vs 15/42).

4 We conclude that chronic use of anticonvulsants enhances clinical features of paracetamol toxicity and discuss possible mechanisms by which this could be mediated.
Chromosomal Aberrations and Sister-Chromatid Exchange Frequencies in Workers Occupationally Exposed to Textile Dyes
Authors: Mohan Kumar R. , Chandrasekar R. , Rani M.V.U.
Published: December 2008

The peripheral lymphocytes of 11 male and seven female workers occupationally exposed to textile dyes were studied for cytogenetic change. A significant increase in the frequency of chromosomal aberrations and sister chromatid exchanges were recorded regardless of the duration of the workers' exposure to the dyes.
The Role of Ecotoxicology in the Assessment of Human Exposure to Chemical Substances
Authors: Calamari D.
Published: December 2008

In the late 1970s new legislation was established in many industrialized countries in order to protect the environment. This has led to the definition of a new branch of science: ecotoxicology. The development of predictive approaches for the hazard assessment of chemical substances has given increased relevance to exposure evaluation. This paper discusses the problems related to the environmental distribution and fate of chemicals and their potential use in the assessment and prediction of exposure of the general population, through air, drinking water and food.

Collaboration between toxicologists and ecotoxicologists is urged to improve our capability to manage chemicals.
A Pattern of Acute Poisoning in Children in Urban Zimbabwe: Ten Years Experience
Authors: Kasilo Ossy M.J. , Nhachi Charles' F.B.
Published: December 2008

1 A retrospective analysis was performed to evaluate the epidemiology of poisoning in children based on admissions to six of Zimbabwe's main urban hospitals over a 10-year period from 1980 to 1989 inclusive.

2 A total of 2873 cases were children aged between 0-15 years. This constituted 47.8% of poisoning cases from all age groups (6018) recorded during the study period.

3 All of the children (0-15 years) had signs and symptoms of poisoning on admission and, depending on their severity, were admitted to a ward or to an intensive care unit. A total of 4.9% (141) died. Most of those who died were suicide cases among the 11-15 year age group and accidental poisonings among the 0-15 year old group.

4 The under 0-5 age group constituted the majority of cases (75.4%) in the 0-15 age group, and most were between 1 and 3 years old. The 6-10 and 11-15 age groups formed 12.6% and 12% of the cases, respectively. The sex distribution showed that 53.1% were male.

5 Most incidences were accidental (93.2%). Suicides and parasuicides accounted for 1.9% and there were only two homicides.

6 The commonest toxic agents were: household products (27.2%), traditional medicines (23.%), venoms from snake bites and insect stings (16%) and therapeutic agents (12.4%). Of the therapeutic agents the most frequently implicated were antipsychotics 18.9%, analgesics 16.8%, anti-infectives 11.7%, anticonvulsants (8.2%) and benzodiazepines (7.7%).

7 The incidence of poisoning could be significantly reduced by health education directed at parents with emphasis on the safe storage of paraffin, drugs and household chemicals. An improvement in living conditions would also offer direct benefits.
Lack of Acipimox-Digoxin Interaction in Patient Volunteers
Authors: Chijioke Chioli Pascal , Pearson Richard Martin , Benedetti Strolin
Published: December 2008

1 A study was carried out to find out if digoxin and acipimox interact.

2 Six elderly patients on digoxin were each given acipimox 150 mg three daily for a week, after informed consent. Digoxin and acipimox plasma concentrations and urinary excretion were measured after the first dose of acipimox and after a week of treatment.

3 Data were fitted to a one-compartment oral absorption model. Areas under the plasma concentration-time curve, plasma and renal clearances, and elimination half-life were computed.

4 There was no significant difference in digoxin plasma concentrations and kinetic parameters before and after acipimox administration. Acipimox kinetics were not affected by the concomitant ingestion of digoxin.

5 The patients' clinical condition remained stable during the study.

6 Thus there was no evidence for an adverse interaction between digoxin and acipimox in human subjects under the conditions of this study.
Clinical Course, Therapy, Outcome and Analytical Data in Amitriptyline and Combined Amitriptyline/Chlordiazepoxide Overdose
Authors: Köppel C. , Wiegreffe A. , Tenczer J.
Published: December 2008

A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2), treated at our Intensive Care Unit or reported to our Poison Information Center between 1985-1990, were evaluated with respect to clinical course, symptoms and outcome, as well as efficacy of therapy. The mean amount of AT was considerably higher in group 1 compared to group 2 (13 mg kg-1vs 7.7 mg kg-1). The most frequent symptoms in both groups were impaired consciousness, anticholinergic symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency necessitated respirator therapy in 63 of the patients. Two patients in group 1 and one patient in group 2 did not survive.

Therapy included primary detoxification by gastric lavage and repeated administration of activated charcoal. In four of eight patients with cardiac conduction disturbances, hypertonic sodium bicarbonate led to a significant reduction in QRS duration and AV interval. Physostigmine was effective in eight of 14 patients with pronounced anticholinergic symptoms. No effect was observed in the other six patients. Haemoperfusion, which was performed in five patients, led to rapid improvement of coma after initiation of therapy in four patients. The clinical efficacy of haemoperfusion in AT overdose despite the high volume of distribution of AT deserves further investigation.

The rather high average overdose of AT implies that large package sizes of AT were available to the patients. A major step towards prevention of serious AT overdose would be the prescription of package sizes containing a total amount of less than 500 mg AT.

Different analytical methods (enzyme immunoassay, fluorescence polarization immunoassay, and gas chromatography/mass spectrometry) for rapid detection of AT and its metabolites in plasma and urine were evaluated. Commercially available immunoassays like EMIT and ADX were highly reliable and sensitive in the detection of AT overdose. Five previously unknown metabolites or derivatives of AT could be detected in cases of AT overdose with the aid of a gas chromatography/mass spectrometry screening procedure.
Podophyllotoxin Intoxication: Toxic Effect of Bajiaolian in Herbal Therapeutics
Authors: Kao Wei-Fong , Hung Dong-Zong , Tsai Wei-Jen , Lin Kon-Ping , Deng Jou-Fang
Published: December 2008

Bajiaolian ( Dysosma pleianthum), one species in the Mayapple family, has been widely used as a general remedy and for the treatment of snake bite, weakness, condyloma accuminata, lymphadenopathy and tumours in China for thousands of years. However, the textbooks of traditional Chinese medicine mention little about the toxicity of Bajiaolian. Within 1 year, the authors saw five people who manifested nausea, vomiting, diarrhoea, abdominal pain, thrombocytopenia, leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistant peripheral tingling or numbness after drinking infusions made with Bajiaolian. The herb was recommended by either traditional Chinese medical doctors or herbal pharmacies for postpartum recovery and treatment of a neck mass, hepatoma, lumbago and dysmenorrhoea. Podophyllotoxin is one of the main ingredients of the Bajiaolian root. The clinical manifestations observed in our patients were consistent with podophyllum intoxication. Podophyllotoxin intoxication usually results from the accidental ingestion or topical application of podophyllum resin. However, these cases of Bajiaolian intoxication were iatrogenic and results from 'therapeutic doses' of Bajiaolian cited in the textbooks of traditional Chinese medicine.
Long-Term Study of Brain Lesions Following Soman, in Comparison to DFP and Metrazol Poisoning
Authors: Kadar T. , Cohen G. , Sahar R. , Alkalai D. , Shapira S.
Published: December 2008

The long-term histopathological effects of acute lethal (95 μg kg-1) and sublethal (56 μg kg-1) doses of soman were studied in rats and were compared to lesions caused by equipotent doses of either another cholinesterase (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant, metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose administration of all the compounds, yet only soman induced brain lesions. Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced some histological changes without any clinical signs of intoxication.

Soman-induced brain lesions were assessed quantitatively using a computerized image analyser. The analysis was carried out for up to 3 months following administration, and a dynamic pattern of pathology was shown. The cortical thickness and area of CA1 and CA3 cells declined significantly as early as 1 week post-exposure. No pathological findings were detected following DFP and metrazol administration. It is therefore suggested that brain lesions are not common for all ChE inhibitors and that convulsions per se are not the only factor leading to brain damage following the administration of soman. The degenerative process (found also with the sublethal dose of soman) might be due to a secondary effect, unrelated to soman's clinical toxicity, but leading to long-term brain injuries.
Diquat-Induced Intestinal Secretion in the Anaesthetized Rat
Authors: Rawlings John M. , Foster John R. , Heylings Jon R.
Published: December 2008

1 Diquat (1,1'-ethylene-2,2'-bipyridilium) is a non-selective desiccant herbicide which, when administered orally to mammalian species, causes significant secretion of fluid into the lumen of the gastrointestinal tract. In order to characterize this secretory response in more detail the effect of sublethal doses of diquat dibromide (DQBr2) on intestinal secretion was investigated in vivo in the jejunum of anaesthetized rats.

2 Ligated segments of jejunum (10 cm) which were prepared in groups of up to five animals were filled with 500 μl of isosmotic DQBr2 solutions with concentrations ranging from 1-100 mM and maintained in the anaesthetized rat for 1, 2 or 3 h; in control experiments a solution of 100 mM NaBr was used.

3 It was found that while all of the fluid instilled into the segments was absorbed in the control experiments, there was both a dose- and time-dependent secretory response to DQBr2. Maximal fluid secretion occurred after treatment with 50 mM DQBr2 for 3 h.

4 Histological assessment of the jejunum revealed an increase in cell exfoliation and evidence of luminal distension after incubation with DQBr2. However, no structural damage to the mucosa could be seen to account for the fluid secretion.

5 The model described provides a quantitative means of evaluating intestinal secretion and may be used for elucidating the mechanism by which diquat alters fluid transport processes.
Clinical Experience in the Therapy of Bites from Exotic Snakes in Berlin
Authors: Köppel C. , Martens F.
Published: December 2008

Since there are nearly no indigenous poisonous snakes in Germany, snake bites by poisonous snakes are rare. Most serious snake bites reported to poison information centres or treated at hospitals are caused by exotic snakes that are kept in private households. Only few types of antivenom are stored in emergency depots in Germany including polyvalent antivenoms from commercial sources. Since experience with the treatment of poisonous snake bites is limited, the records of the Intensive Care Unit and the Poison Information Centre of the Universitätsklinikum Rudolf Virchow from 1980-1991 were evaluated. During this period, 51 snake bites were reported. Eleven patients who had been bitten by exotic poisonous snakes were treated in intensive care. In eight of the cases, ethanol (blood levels on admission 1.2-4.2 g-1) had played an important role in the cause of the bite. A moderate to severe local inflammation at the site of the bite followed by oedema and necrosis was typical. One patient developed respiratory failure, probably because of the neurotoxic effects of the snake venom and a compartment syndrome necessitating fasciotomy. Haemolysis was observed in four patients and coagulopathy in six patients. All patients received polyvalent antivenom within 2-12 h of the snake bite. Despite serious coagulopathy in two of the patients and respiratory arrest in one, all survived without sequelae.
Medical Charcoal for a Child's Poisoning at Home: Availability and Success of Administration in Finland
Authors: Lamminpää A. , Vilska J. , Hoppu K.
Published: December 2008

In a prospective study, 174 families were interviewed over the telephone to find out whether the treatment of their child's poisoning with medical charcoal was successfully completed. The majority (103; 59.2%) of the families had no charcoal at home. The mean delay in administration for those who had to obtain charcoal was 41.6 min; significantly longer than the 24.5 min taken for those who had charcoal at home (P<0.001 ). The treatment succeeded in all but five of the 102 patients given charcoal at home. Thus for mild poisoning in young children, the administration of activated charcoal at home, under the guidance of a Poison Information Centre, could be a rapid and safe first-aid treatment. Presently the widespread unavailability of charcoal in the home in Finland causes an unnecessary delay in treatment that could be of clinical importance.