bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety Warnings and First Aid Instructions on Consumer and Pharmaceutical Products in Nigeria: are they Adequate?
Authors: Orisakwe Orish Ebere
Published: December 2008

An investigation into the adequacy of safety warnings and first aid instruction on 357 consumer and pharmaceutical product labels was carried out. The results show that 23% of the products carried correct and appropriate information while 34% had neither warning nor first aid instructions. About 15% had copiously written instructions and/or warnings and 15% showed partially correct instructions. Only about 4% of the products described warning signs and gave directions for the full treatment of poisoning and 3% recommended calling a health professional in the case of poisoning.
Mobilization and Distribution of Beryllium Over the Course of Chelation Therapy with Some Polyaminocarboxylic Acids in the Rat
Authors: Mathur Seema , Flora S.J.S. , Mathur R. , Das Gupta S.
Published: December 2008

The efficacy of three common polyaminocarboxylic acids in the treatment of experimental beryllium intoxication was investigated in male rats. N-(2-hydroxyethyl) ethylene diamine triacetic acid (HEDTA) was more effective than calcium disodium ethylenediamine tetraacetic acid (CaNa2EDTA) in reducing the beryllium concentration of the blood, kidneys and spleen and reducing beryllium-induced inhibition of hepatic alkaline phosphatase activity. HEDTA was also most effective in reducing histopathological lesions in the liver and spleen. Compared to these two chelators, the third amino chelator, calcium trisodium diethylene triaminepenta acetic acid (CaNa3DTPA) produced severe deleterious effects in the liver and systemic toxicity. The results suggest that HEDTA is a promising chelator for beryllium toxicity while DTPA enhances the toxic manifestation of beryllium.
Protection against Cyanide Poisoning by the Co-administration of Sodium Nitrite and Hydroxylamine in Rats
Authors: Bhattacharya R. , Jeevaratnam K. , Raza S.K. , Das Gupta S.
Published: December 2008

1 The protectiveness of combined treatment with sodium nitrite (SN) and hydroxylamine (HA) in cyanide intoxication was investigated in male rats.

2 Pretreatment with equimolar dose of SN or HA produced a significant protection against cyanide poisoning as shown by the protection index (LD50 of cyanide in protected rats/LD50 of cyanide in saline-treated rats).

3 The co-administration of SN and HA as a split dose produced an optimal and sustained methaemoglobinaemia.

4 Pretreatment with combined SN and HA administration at different time intervals offered sustained protection against cyanide and resultant cytochrome oxidase inhibition.

5 Adjunction of sodium thiosulphate (STS) in the SN + HA regimen further augmented the protection against cyanide poisoning.

6 The results suggest that pretreatment with SN + HA co-administration could significantly reduce the toxic manifestation of cyanide.
Camelford Water Poisoning Accident; Serial Neuropsychological Assessments and Further Observations on Bone Aluminium
Authors: McMillan T.M. , Freemont A.J. , Herxheimer A. , Denton J. , Taylor A.P. , Pazianas M. , Cummin A.R.C. , Eastwood J.B.
Published: December 2008

The serial cognitive assessment of ten individuals made between 8 and 26 months after the water at Camelford in Cornwall was accidentally contaminated with aluminium sulphate, showed consistent evidence of impairment of information processing and memory. There was no obvious relationship between these impairments and measurements of anxiety and depression.

Serial bone biopsies in two individuals showed that the aluminium which was present 6 and 7 months after the accident had disappeared by 19 months. In the eight individuals biopsied 12-17 months after the accident the bone showed no stainable aluminium.

Thus, aluminium deposited in the bone of normal individuals can disappear within 18 months. After an accident such as that at Camelford important evidence of toxicity is likely to be missed if an investigation is delayed. The abnormal neuropsychological findings indicate cognitive impairment, but whether this was caused by an acute episode of brain damage, or other causes such as the psychological effects of stress resulting from the accident, is uncertain.
Identification of Epithelial Cells in Bronchoalveolar Lavage
Authors: Finotto Susetta , Rado Vanda , Dal Vecchio Aldo , Milani Gianfranco , Fabbri Leonardo M. , Maestrelli Piero
Published: December 2008

1 Damage to the bronchial epithelium occurs after the inhalation of toxic substances and allergens, and through virus infections and it may lead to increased desquamation of epithelial cells in bronchoalveolar lavage (BAL).

2 In this study we compared two methods of staining the epithelial cells of BAL, the conventional cytochemical May Grunwald-Giemsa stain (MGG) and an immunocytochemical technique using a monoclonal antibody anti-human cytokeratin (CK) detected with APAAP immuno-alkaline phosphatase. BAL was obtained from 13 subjects and the epithelial cells were cytocentrifuged either immediately after collection (fraction A) or after washing (fraction B).

3 Higher percentages of epithelial cells were identified in fraction A with CK (20.0 ± 5.1 %) than in fraction A with MGG (11.2 ± 2.3%), which recognized only ciliated epithelial cells. In fact a proportion of CK-positive cells (34%) in fraction A were not ciliated. Underestimation of epithelial cells by MGG compared to CK was more pronounced in fraction B (8.0 ± 2.9% and 22.9 ± 3.0%, respectively) as there was a relative loss of ciliated CK+ cells after washings.

4 These results suggest that immunocytochemical staining with an anti-cytokeratin monoclonal antibody is more sensitive than using the MGG stain in detecting epithelial cells in BAL.
Poisoning due to Insect and Scorpion Stings/Bites
Authors: Nhachi Charles F.B. , Kasilo Ossy M.J.
Published: December 2008

1 A retrospective study, 1980 to 1989 inclusive, of hospital admission cases due to insect and scorpion stings or bites was carried out in the six main central hospitals of Zimbabwe's four main cities.

2 A total of 92 cases were recorded and analysed. This constituted 1.5% of all hospital admissions for poisoning which were analysed during that time.

3 Of the 92 cases the highest number of victims were seen in the 2-to-5-year age group (29.3%), followed by the 6-to-10-year age group (23.9%). In other age groups the incidence of poisoning was distributed approximately evenly with the 41 to 50 and the over 60-year age groups having the least number of victims, (2.2%).

4 The main groups of insects associated with poisoning were bees, 44.6%; wasps, 8.7%; and spiders 8.7%. A further 32.6% of the insect stings were not specified. Scorpion stings accounted for 5.4% of incidences.

5 No fatalities occurred.

6 Treatment consisted mainly of the administration of promethazine, as an antihistamine in 35% of the cases, steroids (16.5% of the cases), perhaps for their anti-allergic effects, and paracetamol, a mild analgesic, (14.7% of the cases). Interestingly, 22.6% of the cases were given an antibiotic (14.1 % of which were penicillins). Adrenaline was administered in only 1.7% of the cases.

7 The majority of the recorded cases, 49.4%, were hospitalized for at least a day and the average duration of hospitalization was 6.4 days.
Short-Term Effect of Various Doses of Cyclosporin A on Plasma Lipoproteins and its Distribution in Blood: An Experimental Study
Authors: Andrade R.J. , Lucena M.I. , Gonzalez-Correa J.A. , Garcia-Arias C. , Gonzalez-Santos P.
Published: December 2008

Hyperlipidaemia commonly develops in both transplant recipients and experimental animals receiving cyclosporin A (CsA). However, the threshold of CsA induced-changes on lipoproteins and the role of parenteral vehicle (cremophor) has not been defined.

Male Wistar rats were classified into five groups of six animals each and received CsA in cremophor vehicle at doses of 5, 10 or 20 mg kg-1 d-1, s.c., vehicle alone or saline for 7 d. Blood was obtained 24 h after the last dose and plasma was analysed. Plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein subfractions (HDL-2, HDL-3) were isolated by sequential ultracentrifugation and their content of cholesterol, triglyceride and phospholipid was determined. Whole blood and trough plasma CsA levels were measured by monoclonal radioimmunoassay.

Plasma lipids did not differ significantly among the five groups. At a dose of 20 mg kg-1 d-1 of CsA VLDL cholesterol rose significantly (P<0.05). Administration of either CsA or cremophor vehicle increased HDL-2 phospholipids (P<0.05) and decreased HDL-3 cholesterol. There was not a linear relationship between whole blood and plasma CsA levels and increasing CsA doses.

Short-term treatment with low doses of CsA have little influence on lipid profile in the rat. Changes on lipoprotein composition can be attributed mainly to cremophor vehicle, conceivably due to its ethanol content.
The Effects on Rat Thyroid Function of an Hepatic Microsomal Enzyme Inducer
Authors: Johnson S. , McKillop D. , Miller J. , Smith I.K.
Published: December 2008

1 Following daily administration to male albino rats for 2 weeks, β-naphthoflavone (25 and 60 mg kg-1, i.p.) and phenobarbitone (100 mg kg-1, p.o.) produced their characteristic patterns of induction of P450-related enzyme activities. β-naphthoflavone also induced p-nitrophenol glucuronidation by 160% over controls, while phenobarbitone produced only a 45% induction of this conjugation activity.

2 β-Naphthoflavone produced significant reductions in plasma thyroxine (T4) concentrations on days 4 and 16 and also decreased tri-iodothyronine (T3) on day 4. Thyroid-stimulating hormone (TSH) was significantly increased on day 16 by the higher dose of β-naphthoflavone. Thyroid weight was significantly increased at both dose levels on day 16 and liver weight was significantly increased on both days 4 and 16. No histopathological changes were seen in the liver or pituitary, but 30% of the animals showed minimal to mild follicular epithelial hypertrophy of the thyroid gland.

3 Phenobarbitone had no effect on T4concentrations, but significantly decreased T3on day 4. TSH increased by 60% on day 16, but was not statistically significant compared with controls. Thyroid weight was significantly increased on day 16 and liver weight was significantly increased on days 4 and 16. Mild to moderate thyroid follicular epithelial hypertrophy and moderate hepatocyte hypertrophy occurred in all animals. No histopathological changes were seen in the pituitary.

4 The early changes in T4and/or T3were probably due to increased hepatic clearance by induction of thyroxine glucuronidation with both compounds. Thyroid hypertrophy would be expected to follow as a result of activation of the hypothalamic-pituitary-thyroid axis. Data for the two compounds suggest some variation in the precise mechanism of action, which has not yet been fully elucidated.
An investigation of Urinary Creatine Excretion as a Potential Marker for Testicular Damage
Authors: Nahas Kamil , le Net Jean-Loic , Provost Jean P. , Tomaszewski Konrad E.
Published: December 2008

1 This study assessed urinary creatine excretion as a marker for testicular atrophy.

2 Male rats received a single i.p. dose of 2-methoxyethanol at 0, 250 or 750 mg kg-1 and were sacrificed 2 d later. Urinary creatine and creatinine excretion were measured on days 0, 1 and 2.

3 Decreased testicular weights and histopathological assessment revealed dose-related testicular damage.

4 On day 1, at both doses of 2-methoxyethanol, urinary creatine levels increased and creatinine levels decreased, resulting in a dose-related increase in the creatine/creatinine ratio. On day 2, the creatine/creatinine ratio was elevated relative to controls, but was less marked than on day 1.

5 The study confirmed that creatine excretion is a potential marker for acute testicular damage.
Effect of Flumazenil in a Model of Acute Alcohol Intoxication in Rats
Authors: Lheureux P. , Fontaine J. , Askenasi R.
Published: December 2008

The ability of high doses of flumazenil to antagonize ethanol-induced sedation was assessed via ethanol-induced loss of the righting reflex (LRR) in rats. Ethanol (3.5-5 g kg-1i,p) produces a dose-dependent increase in the proportion of animals presenting a LRR response. Flumazenil (0.1 to 1 mg kg-1i.p) was ineffective in preventing the suppression of the righting reflex and even aggravated it for ethanol dosages of 3.5 and 4.0 g kg-1. These data support the view that flumazenil has no effective 'anti-ethanol' properties. Conversely, the prolongation of mean sleep time provoked by the antidote could be related to the suppression of a putative endogenous inverse-agonist activity at the benzodiazepine receptor, which could be implicated in the mechanism of the acute tolerance to ethanol.
Modelling Dermal Pharmacokinetics Using in vitro Data. Part II. Fluazifop-butyl in Man
Authors: Auton T.R. , Ramsey J.D. , Woollen B.H.
Published: December 2008

In a previous paper it was demonstrated that dermal absorption of the herbicide fluazifop-butyl in the rat could be modelled by combining a knowledge of the pharmacokinetics following intravenous and oral dosing with in vitro measurements of dermal absorption. This paper demonstrates the validation of a similar model for the dermal absorption of fluazifop-butyl in man. Pharmacokinetic parameters derived from an oral dosing study are combined in a mathematical model with in vitro measurements of dermal absorption of fluazifop-butyl. Model predictions of the rate and extent of dermal absorption of fluazifop-butyl are compared with the results of dermal absorption studies in human volunteers. Good agreement is found between the model predictions and the experimental measurements. These results have implications for improved risk assessment. The model provides a tool for risk assessment based on both internal dose (e.g. peak plasma concentration, plasma area under the curve) as well as total absorbed dose. However, further work is required to evaluate whether the same techniques are applicable to a wider range of compounds.
Removal of Inhaled Plutonium and Americium from the Rat by Administration Of ZnDTPA in Drinking Water
Authors: Stradling G.N. , Gray S.A. , Ellender M. , Pearce M. , Wilson I. , Moody J.C. , Hodgson A.
Published: December 2008

This study has examined the efficacy of ZnDTPA administered in drinking water for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates; the dosage used was 95 μmol kg-1d-1. The continuous administration of ZnDTPA over a 14 d interval, commencing 1 h after exposure, reduced the lung and total body contents of 238 Pu to, respectively, 11 % and 18% of those in untreated rats; the corresponding values for 241Am were 11 % and 14%. After the continuous administration of 95 μmol kg-1 from 4 d to 28 d post exposure, the lung and total body contents of 238Pu were, respectively, 5% and 16% of those in controls; the corresponding values for 241Am were 7% and 19%. Further reductions in the actinide contents of body tissues were found when treatment was extended to 52 d or 76 d. These regimens were as effective as twice weekly injections of 30 μmol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 μmol kg -1 d-1 for 72 d, some pathological changes to the gastrointestinal tract were observed but these were considered to be reparable. It was concluded that further work is required to evaluate the toxicity of the ligand and to establish the optimal treatment regimen.
Effect of Fentanyl, Ketamine and Thalamonal on some Biochemical Parameters in Ethanol-Treated and Untreated Dogs
Authors: Gvozdenović Lj.V. , Popović M.R. , Jakovljević V.S. , Lukić V.
Published: December 2008

The effects of fentanyl, ketamine and thalamonal on some biochemical parameters of ethanol-treated and untreated dogs, were studied. The study was carried out on mongrel dogs. The animals were divided into two main groups: one which had free access to food and to 12% (v/v) ethanol, instead of water, and a control group which had food and water ad libitum. The animals in both groups were exposed to the action of anaesthetics for 3 h. The results show that, under the given experimental conditions, the anaesthetics did not significantly change the investigated parameters of blood and liver, either in ethanol-treated or untreated dogs. However, the action of ethanol caused remarkable changes in almost all the investigated parameters. An increased content of cytochrome P450 caused by the action of ethanol suggests possible changes in the metabolism of anaesthetics, which should be of concern to anaesthetists when dealing with patients potentially intoxicated with ethanol.
Chromosomal Aberrations Induced by Methyl Parathion in Human Peripheral Lymphocytes of Alcoholics and Smokers
Authors: Sunil Kumar K.B. , Ankathil Raveendran , Devi K.S.
Published: December 2008

1 Two different concentrations (0.08 and 0.16 μg ml-1) of methyl parathion (MP), a broad-spectrum insecticide, were tested on peripheral lymphocytes of healthy non-smoking non-alcoholics (CN), chronic smokers (SM) and alcoholics with smoking habit (ALSM).

2 SM and ALSM revealed a significant increase in chromosome aberration frequencies in peripheral lymphocytes compared to the CN group.

3 MP did not induce chromosomal aberrations in vitro in the CN group at either of the concentrations tested.

4 In SM and ALSM , MP induced a significant increase in chromosomal aberrations in vitro in peripheral lymphocytes at a concentration of 0.16 μg ml-1.

5 The results indicate that the damage induced by MP in peripheral lymphocytes is potentiated by smoking and alcohol intake.
A Scale to Assess Severity in Organophosphorus Intoxication: POP Scale
Authors: Senanayake Nimal , de Silva H.J. , Karalliedde Lakshman
Published: December 2008

We have developed a clinical scale to assess severity of organophosphorus (OP) intoxication. Five common clinical manifestations of OP poisoning have been selected as parameters, each to be assessed on a 3 point scale varying from 0-2. Poisoning can then be graded as mild (score 0-3), moderate (score 4-7) or severe (score 8-11) when the patient first presents. The scale was validated using two consecutive series of 173 patients with OP poisoning. Correlations between the scores obtained on admission and three outcome variables, namely, death, the need for ventilatory support and the dose of atropine required in the first 24 hours after admission were significant. We believe that this scale would assist in grading severity of OP intoxication at first contact and help in predicting possible outcome.
Biochemical Changes Associated with Muscle Fibre Necrosis after Experimental Organophosphate Poisoning
Authors: Vanneste Yves , Lison Dominique
Published: December 2008

1 This study was initiated to ascertain the possibility of biochemically monitoring the rhabdomyonecrosis that occurs after organophosphate poisoning. The evolution of different parameters has been assessed in the rat 6, 16, 24 and 48 h following 0.67 x LD50 of soman.

2 Acetylcholinesterase (AChE) was inhibited to 60% of the control value in the diaphragm at 6 and 16 h and serum ChE levels inhibited to an average of 30% of the control value. At 24 h, total blood, brain and diaphragm AChE were inhibited by 40, 69 and 38%, respectively.

3 Rhabdomyonecrosis lesions occurred in the diaphragm after 24 h and were accompanied by a concurrent increase in urinary creatine excretion rate (300% of the control) and serum total creatine phosphokinase activity (280% of the control). Calcium-activated neutral protease and phosphorylase a activities were elevated in the muscle at the same time.

4 These biochemical markers will prove useful for investigating the possible relationships between the different neuromuscular syndromes occurring in the course of an OP poisoning and potential therapeutic or protective pharmacological measures.
Plasma Lipid Profile in Rats with Gentamicin-Induced Nephrotoxicity
Authors: Abdel-Gayoum A.A. , Ali B.H. , Ghawarsha K. , Bashir A.A.
Published: December 2008

1 Administration of gentamicin to rats at doses of 20, 40 or 80 mg kg-1d-1for 6 days induced nephrotoxicity exhibited by elevated plasma creatinine concentration and a decrease in alkaline phosphatase activity in rat kidney cortex.

2 Gentamicin treatment produced significant elevation in plasma total cholesterol amounting to 70% at the 80 mg kg-1dose. At this dose, the combined cholesterol fractions of low density and very low density lipoproteins increased by more than two-fold.

3 Gentamicin treatment also caused significant increase in plasma triglyceride concentration, while plasma phospholipid levels showed dose-dependent reductions.

4 In another experiment recovery of the aforementioned parameters was assessed 7 and 14 days after the withdrawal of gentamicin, administered at a dose of 40 mg kg-1d-1for 6 days. After 7 days from drug discontinuation, both plasma creatinine and total cholesterol concentrations returned to the control levels, while triglyceride concentration was still significantly higher than control 14 days after stoppage of treatment.

5 Plasma phospholipid concentration and the activity of cortical alkaline phosphatase were still significantly lower than control 14 days after cessation of the treatment.
Studies on the Mechanism of 4-Aminophenol-induced Toxicity to Renal Proximal Tubules
Authors: Lock Edward A. , Cross Theresa J. , Schnellmann Rick G.
Published: December 2008

4-Aminophenol (PAP) is known to cause nephrotoxicity in the rat where it produces selective necrosis to renal proximal tubules. The aim of this work was to investigate the toxicity of PAP and its known nephrotoxic metabolite 4-amino-3-S-glutathionylphenol using a well defined suspension of rabbit renal proximal tubules. PAP at a concentration of 0.5 mM and 1 mM caused proximal tubule cell death (measured by lactate dehydrogenase release) in a time-dependent manner over a 4-h exposure. In contrast, 4-amino-3-S-glutathionylphenol at 1 mM produced no proximal tubule cell death over a similar 4-h exposure. At 2 h, 1 mM PAP inhibited proximal tubule respiration by 30% and decreased cellular adenosine triphosphate (ATP) levels by 60%. These events preceded cell death. The addition of PAP to proximal tubules led to a rapid depletion of cellular glutathione, exposure to 0.5 mM causing a 50% depletion within 1 h. The cytochrome P-450 inhibitors SKF525A (1 mM) and metyrapone (1 mM), the iron chelator deferoxamine (1 mM) and the antioxidant N,N'-phenyl-1,4-phenyienediamine (2 μM) had no effect on PAP-induced cell death. However ascorbic acid (0.1 mM), afforded a marked protection against the depletion of cellular glutathione and completely protected against the cell death produced by 1 mM-PAP. These results indicate that oxidation of PAP to generate a metabolite that can react with glutathione is an important step in the toxicity, while mitochondria appear to be a critical target for the reactive intermediate formed.
Malaoxon-Induced Brain Phosphoinositide Turnover and Changes in Brain Calcium Levels by Female Gender in Pregnant and Non-Pregnant Convulsing and Non-Convulsing Rats
Authors: Hirvonen M.-R. , Savolainen K.M.
Published: December 2008

Alterations in malaoxon-(MO)-induced brain regional phosphoinositide (PI) turnover and in brain calcium levels were studied in female non-pregnant and pregnant rats, and in their offspring. The adult rats were followed for 1 or 4 h after MO for tonic-clonic convulsions. A dose of 8.2 mg kg-1of MO caused similar convulsions in 74% of the pregnant rats as we have reported in young male rats with a dose of 39.2 mg kg-1,1However, convulsions did not occur in non-pregnant female rats. Inositol and inositol monophosphate levels were similar in all control rats. MO decreased brain inositol both in pregnant and non-pregnant female rats, and in the cerebellum of the offspring. In contrast to the findings in male rats, MO only randomly increased brain inositol-1-phosphate in female rats, or in their offspring. However, cerebral inositol-4-phosphate levels were similarly increased both in the non-pregnant and the pregnant rats irrespectively of convulsions. MO did not elevate cerebral Ca2+in female rats or their offspring, in contrast to the male rats.1The present results suggest that female rats are more sensitive than male rats to MO-induced PI signalling, and during pregnancy, also to MO-induced overt convulsions, but not to changes in cerebral Ca2+.
The Role of In Vitro Experiments in Animal Welfare
Authors: Rasmussen Eva Selzer
Published: December 2008

The prospects of replacing animal experiments with other types of toxicological studies are considered, and the use of human data and in vitro experiments are discussed. Ongoing validation studies of in vitro methods for evaluation of acute toxicity, local irritation, target organ toxicity, tumour promotion and teratogenicity are presented.
Toxicological Testing in the European Community
Authors: van der Venne Marie-Thérèse , Berlin Alexander
Published: December 2008

This paper provides a brief overview and guide to the development of European Community regulatory policy in relation to toxicology.
A Five Year Review of Fatal Self-Ingested Overdoses Involving Amitriptyline in Edinburgh 1983-'87
Authors: Bolster Margot , Curran Julie , Busuttil Anthony
Published: December 2008

One hundred and twelve cases of fatal self-ingested overdoses were investigated in the Forensic Medicine Unit of the Department of Pathology of the University of Edinburgh in the period 1983-'87 (inclusive). Of these, 24 cases involved amitriptyline as either the sole agent or in combination with another drug, the most common of which was ethanol. The mean age of the latter group was 43 years with a marked female preponderance. The social history was documented with six out of the 24 cases living alone and five out of the 24 cases divorced. The number previously referred for psychiatric treatment and the number of cases where over 100 tablets of the drug had been prescribed at any one time (where known) was recorded: eight out of 24 cases. The fact that amitriptyline was by far the commonest of the tricyclic antidepressants to be encountered in a fatal overdose situation raises the important question of the prescribing of amitriptyline as a first line therapy in mental depression.
The Teratogenic Metabolites of Vitamin A in Women Following Supplements and Liver
Authors: Buss N.E. , Tembe E.A. , Prendergast B.D. , Renwick A.G. , George C.F.
Published: December 2008

1 Ten healthy female volunteers were given 5 doses of retinol as the palmitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg as fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection.

2 Plasma concentrations of retinyl palmitate were higher after 50 mg retinol given as an oral supplement compared with 50 mg as liver; there was no significant difference between the 150 mg doses. Plasma concentrations of retinol showed only small increases.

3 The peak plasma concentrations (Cmax) of all- trans-retinoic acid, the principal teratogenic metabolite of retinol, and the area under the concentration-time curve (AUC) were up to 20-times higher after supplements compared to the same dose as liver. Plasma concentrations of all- trans-4-oxo-retinoic acid, 13- cis-retinoic acid and 13- cis-4-oxo-retinoic acid showed smaller differences between supplements and liver.

4 Intra-muscular administration of 30 mg retinol gave retinyl palmitate concentrations similar to those found after the oral doses but did not increase circulating concentrations of the acid metabolites.

5 Based on the formation of all- trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the consumption of liver based on the reported teratogenicity of vitamin A supplements should be reconsidered.
An Immunological Study on Workers Occupationally Exposed to Cadmium
Authors: Karakaya A. , Yücesoy B. , Sardas O.S.
Published: December 2008

1 To assess the quantitative relation between exposure to airborne cadmium and various markers of immune function, 37 male workers were examined and compared with unexposed controls.

2 Blood cadmium concentrations were signficantly , higher in the exposed workers than in the unexposed, as was urine cadmium.

3 No differences in the serum immunoglobulin (IgG, IgM and IgA) levels between two popularions were observed, There was also no significant correlation between blood cadmium concentrations and serum immunoglobulin levels of both exposed and control groups, It has been found also that while monocyte counts signficantly increased, lymphocyte, neutrophil and oesinophil counts remained unchanged.
Influence of Protein Malnutrition on Teratogenicity of Acetylsalicylic Acid in Rats
Authors: Hamed M.R. , Al-Assy Y.S. , Ezzeldin E.
Published: December 2008

The effect of protein malnutrition (PM) on the embryotoxicity and teratogenicity of aspirin in rats has been studied. Protein malnourishment was produced from Days 7 to 21 of gestation by limiting the casein content of the diet to 5% in comparison to 20% for the normal animals. Six dose levels of aspirin (50-175 mg kg-1) were administered p.o. from Days 8 to 11 of pregnancy. Aspirin from 75 mg kg-1 d-1 induced growth retardation, embryolethality and teratogenicity, as shown by external, skeletal and visceral malformations. All these effects were potentiated by protein malnutrition.
Deaths from Pesticide Poisoning in England and Wales: 1945-1989
Authors: Casey P. , Vale J.A.
Published: December 2008

1 Data on deaths from pesticide poisoning occurring in England and Wales between 1945 and 1989 (no data are available for 1954) have been collated; pesticides were responsible for only 1012 (1.1 %) of the 87,385 deaths from poisoning (excluding those due to carbon monoxide) occurring over this 44 year period. At least 73% of all pesticide fatalities were due to suicide and overall there was a predominance of males (male:female ratio 2.4:1). No deaths from pesticide poisoning in children under 10 years have been reported since 1974 although almost 50% of suspected pesticide poisoning incidents involve this age group.

2 Herbicides were responsible for 787 (78%) fatal poisonings, 110 (11%) were caused by insecticides, 69 (6.8%) by rodenticides, 30 (3.0%) by wood preservatives and 16 (1.6%) by other pesticides.

3 The herbicide, paraquat, was responsible for 570 of 1012 (56%) deaths and, although there has been a progressive decline in the annual number of deaths from paraquat poisoning since 1982, paraquat remains the most common cause of fatal pesticide poisoning in England and Wales.

4 Sodium chlorate caused 113 (11.2%) deaths, most of these fatalities occurring between 1965 and 1983; only one death has been recorded since 1984. The phenoxyacetate herbicides resulted in 50 deaths; 2,4-D was implicated most commonly, Sixty-eight deaths were due to organophosphorus insecticides; demeton-S-methyl, malathion and mevinphos were involved most frequently. Only eight deaths resulted from organochlorine insecticides and two of these also involved an organophosphorus insecticide.

5 Although pesticide poisoning is an uncommon cause of admission to hospital in England and Wales, the mortality remains high at least in adult cases due to the suicidal ingestion of paraquat.
Lindane Haematotoxicity Confirmed by In vitro Tests on Human and Rat Progenitors
Authors: Parent-Massin D. , Thouvenot D. , Rio B. , Riche C.
Published: December 2008

Blood dyscrasias such as aplastic anaemia and leukopenia are described following the use of lindane for agricultural purposes or against ectoparasites in animal and human health. In order to determine the involvement of lindane in these effects, an in vitro model of haematotoxicity evaluation has been used.

Culture of haematopoietic progenitors, Colony Forming Unit-Granulocyte and Macrophage (CFU-GM), have been performed in the presence of lindane with increasing concentrations.

Results showed that lindane was cytotoxic for human progenitors. They were one thousand times more sensitive to the lindane than rat CFU-GM.

This cytotoxicity was observed with lindane concentrations similar to those measured in human blood in cases of acute intoxication and in fat tissues of exposed populations.
Vitamin C in CC14 Hepatotoxicity-A Preliminary Report
Authors: Ademuyiwa O. , Adesanya O. , Ajuwon O.R.
Published: December 2008

1 The hepatotoxic effect of CC14 was studied in the rat by using 3 well established liver function tests (plasma glucose, bilirubin and proteins) as indices of hepatic integrity.

2 The protective effect of vitamin C against this hepatotoxicity was also investigated.

3 CC 14 (8 ml kg-1body weight) caused a decrease in the levels of plasma conjugated bilirubin, glucose and protein.

4 Vitamin C (2 g kg-1body weight) prevented liver damage induced by CC14. The possible mechanisms of protection are highlighted.
Comparison of Ketorolac Tromethamine with Other Injectable Nonsteroidal Anti-Inflammatory Drugs for Pain-on-Injection and Muscle Damage in the Rat
Authors: Chellman Gary J. , Lollini Lance O. , Dorr Albert E. , DePass Linval R.
Published: December 2008

The local tolerance of ketorolac tromethamine (Toradol®, Syntex) was compared with that of four other injectable nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium, piroxicam, ketoprofen, and metamizol magnesium) in the rat paw-lick/muscle irritation assay as described previously,1 All drugs were tested at concentrations approved for clinical use. After subplantar (footpad) injection, ketorolac produced virtually no pain-on-injection as assessed by the number of paw-lick/lift responses during a 15 min observation period. The other NSAIDs produced slight to moderate paw-lick/lift responses. Redness and swelling at the injection site were less severe for ketorolac than for the other NSAIDs, After intramuscular (i.m.) injection, all of the. NSAIDs produced some degree of muscle damage, as assessed histopathologically 24 h after injection. The lesions, consisting primarily of muscle degeneration, were less severe for ketorolac than for the other NSAIDs. Ketorolac and metamizol produced the smallest elevations in serum creatine kinase, as measured 2 h after i.m. dosing, not significantly different from isotonic saline. Overall, ketorolac was better tolerated in the assay than the other injectable NSAIDs, thereby suggesting the possibility of improved local tolerance on clinical use.
Calcium Channel Blockin Drug Overdose: an Australian Series
Authors: Howarth D.M. , Dawson A.H. , Smith A.J. , Buckley N. , Whyte I.M.
Published: December 2008

1 A descriptive case study of calcium channel-blocking drug (CCB) overdoses in the Hunter Region of NSW was performed to analyse the in-hospital morbidity and mortality of CCB drug overdoses in an Australian population.

2 The patients were admitted to major hospitals within the Hunter Region and treated initially with gastrointestinal decontamination, including the use of oral activated charcoal. Further management was required in most cases and included intravenous calcium, atropine and inotropic support.

3 Of the 15 CCB overdoses, four patients died. Non-cardiogenic pulmonary oedema occurred in two other cases. Cardiac conduction defects occurred in 11 cases.

4 Atropine was found to be effective only after intravenous calcium had been administered.

5 Overdose with slow-release verapamil required prolonged treatment with intravenous calcium salts.

6 Overdose with verapamil or diltiazem in doses greater than 300 mg carries a significant risk of death and potentially life threatening arrhythmias occur with lower doses.

7 Recommended initial management includes early, effective gastrointestinal decontamination. High dose intravenous calcium salts should be given to reverse hypotension and bradycardia. Atropine and inotropic support are frequently required.
In Vivo Inhibition of Serum Dopamine-β-Hydroxylase by CaNa2 EDTA injection
Authors: De Paris Paola , Caroldi Stefano
Published: December 2008

1 In humans CaNa2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper.

2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning.

3 injection of CaNa2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours.

4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme.

5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed.

6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum.

7 As CaNa2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation.
Biochemical Renal Changes in Workers Exposed to Soluble Nickel Compounds
Authors: Vyskočil Adolf , Senft Václav , Viau Claude , Cížková Milena , Kohout Josef
Published: December 2008

1 Biochemical markers of kidney damage were examined in 14 male and 12 female workers highly exposed to soluble nickel compounds in a chemical plant. The results were compared to those obtained in 12 male and 12 female matched controls.

2 The concentration of nickel in urine of male and female workers averaged 5.0 and 10.3 μg g-1 creatinine, respectively. The mean duration of exposure in male and female workers was 25 and 15 years.

3 No difference was found in the mean urinary excretion of lactate dehydrogenase, albumin and transferrin in both sexes, total proteins, β2microglobulin (β2-m) and retinol-binding protein (RBP) in males and lysozyme in females. Lysozyme and N-acetyl-β-D-glucosaminidase (NAG) were increased in male and total proteins, β2-m, NAG and RBP in female exposed workers. Significant correlations between urinary concentrations of nickel on one side and that of β2-m in women (r = 0.462, P = 0.022) and men ( r = 0.41, P = 0.018) and of NAG in men ( r = 0.405, P = 0.019) on the other side were found in exposed subjects.

4 Results indicate adverse effects of soluble nickel compounds on the kidney tubular function. In agreement with literature data it seems that those effects occur only at high exposure levels.
Fulminant Hepatitis following Exposure to Dichlorohydrin — Report of Two Cases
Authors: Shiozaki Tadahiko , Mizobata Yasumitsu , Sugimoto Hisashi , Yoshioka Toshiharu , Sugimoto Tsuyoshi
Published: December 2008

A 34-year-old man suffered from fulminant hepatitis after cleaning a tank in which there were traces of dichlorohydrin. In spite of daily plasma exchanges, he died 10 days after exposure. A 27-year-old man with much lighter exposure showed only slight liver dysfunction. This is the first report of lethal injury following exposure to dichlorohydrin.
Unusual Manifestations after Malathion Poisoning
Authors: Dive A. , Mahieu P. , Van Binst R. , Hassoun A. , Lison D. , De Bisschop H. , Nemery B. , Lauwerys R.
Published: December 2008

We report a case of organophosphate poisoning with a commercial preparation of malathion (deliberate ingestion of Malathane Garden Spray: malathion 15% in isopropyl alcohol) in which the initial cholinergic crisis was followed by cardiac, pulmonary, neurological and renal manifestations. They occurred when erythrocyte and plasma cholinesterases were reactivating. A chemical analysis of the pesticide preparation revealed, apart from malathion itself, the presence of isopropylmalathion and O,O,S-trimethylphosphorothioate.

Although pure malathion is regarded as one of the safest organophosphate insecticides, this observation underlines the possibility of severe complications after exposure to a preparation which has been stored for a long period of time.
lmmunotoxicological Investigation of SCMF, a New Pyrethroid Pesticide in Mice
Authors: Siroki Olga , Institoris L. , Tatar E. , Desi I.
Published: December 2008

The toxicity of a new pyrethroid pesticide Supercypermethrin Forte (SCMF) was studied in male CFLP mice using classic toxicological (body weight, organ weights) and haematological (white blood cell count, haematocrit, nucleated cell content of femoral bone marrow) methods and immune function tests (PFC assay, DTH reaction).

Four weeks of oral treatment in a 5 days per week system at doses of 1/10, 1/20, or 1/40 x LD50did not cause evaluable changes in the measured parameters. When single calculated LD20, LD10, or LD5doses of SCMF were administered on different days before termination to different groups of mice the two higher doses caused a time- and dose-dependent decrease in the splenic PCF number, Apart from some temporary toxic signs and an increase of haematocrit at the top dose the other examined parameters did not show evaluable changes.

Under these experimental conditions toxic changes appeared only at the high dose range and, of those applied, the PFC assay proved to be the most sensitive method for detecting the toxicity of SCMF.
Deaths from Substance Overdose in the Lothian and Borders Region of Scotland (1983-1991)
Authors: Obafunwa J.O. , Busuttil A.
Published: December 2008

1 A retrospective analysis of 352 consecutive cases of fatal substance overdose that occurred in the Lothian and Borders region of Scotland (LBRS) between 1983 and 1992 (inclusive) is presented. All these cases were subjected to a full forensic autopsy with histological and toxicological studies.

2 The overall male:female ratio is 1,2:1. Males significantly predominate (1.9 :1) in the 21-30 year age group, but females significantly predominate (0.7-0.9:1) above the age of 50 years (P<0.001). A significant progressive alteration in the sex ratio is noted: from 0.7:1 in 1988 to 2.4:1 in 1992 (P<0.001).

3 Analgesics account for 43.2% of all overdose deaths with narcotic analgesics representing 32.4%. Dextropropoxyphene is the commonest (38.2%) narcotic analgesic and fatal overdoses on it have been increasing since 1989; methadone deaths also showed an increase. Death from heroin overdose fell sharply in 1985.

4 Antidepressants account for 20.2% of deaths (tricyclics representing 19.3%): Amitriptyline is the commonest (75.0%) tricyclic and its use, particularly by female suicides, has been increasing since 1989. Barbiturate poisoning has declined considerably since 1986.

5 Temazepam comprises 65.4% of all benzodiazepines overdose deaths; two-thirds of fatal benzodiazepine abuse involve males.

6 This study once more emphasises that physicians, and especially general practitioners, must prescribe cautiously for their patients. Control through legislation of the sale of non-narcotic analgesics is worth serious consideration.
Establishment of Human Tissue Banks
Authors: Bardsley James S.
Published: December 2008

Mounting interest in Europe over the incorporation of the human biological model in the laboratory has been fuelled by scientific advances and the much improved accessibility to human tissue. The collection of tissue is complicated by a host of ethical considerations and lack of public awareness of the benefits of donation to research and education. In the United States, the International Institute for the Advancement of Medicine (IIAM) has been successful in networking the cooperation of organ banks, tissue banks and hospitals, to collect otherwise discarded anatomical gifts with consent from the donor or donor's next of kin for medical research applications. IIAM is a non-profit, non-transplant anatomic bank that is provisionally licensed in the state of New York- one of the first states to implement comprehensive licensing procedures. Over the last year, IIAM has been serving a growing number of investigators in Europe with both fresh and frozen preparations. However, the various logistical problems in transAtlantic transportation and economic considerations warrant the exploration of establishing a satellite bank in Europe that would entail a more efficient and cost effective service to this region. This permanent facility would have access to IIAM's frozen inventory of tissue and tissue-derived protein samples, and would serve to facilitate the provision of fresh tissue, cells and slices to European researchers requiring such materials for their studies.
Comparison of Popliteal Lymph Node Responses in Various Strains of Rats
Authors: Patriarca C. , Verdier F. , Brouland J.P. , Vial T. , Descotes J.
Published: December 2008

Outbred (namely Wistar and Sprague-Dawley) and inbred (Wistar-Furth, Lewis, Fisher 344 and Brown-Norway) strains of rats were screened for their responses to reference compounds in the popliteal lymph node (PLN) assay. Streptozotocin and diphenylhydantoin gave positive responses as evidenced by increased weight and cellularity indices in all strains used whereas procainamide, isoniazid and barbital consistently gave negative responses. Although these findings overall are in agreement with previous investigations involving these compounds, the lack of marked interstrain differences in PLN responses argues against a strong immunogenetically controlled mechanism as could be assumed in presumably auto-immune reactions. The question is raised whether drug-induced side-effects predicted by the PLN assay are basically non-autoimmune as suggested by clinical and immunological findings in man.
Critical Review and Meta-Analysis of Serial Agitated Dilutions in Experimental Toxicology
Authors: Linde Klaus , Jonas Wayne B. , Melchart Dieter , Worku Felege , Wagner Hildebert , Eitel Florian
Published: December 2008

1 We conducted an overview and quantitative meta-analysis of all experimental literature on the protective effects of serial agitated dilutions (SADs) of toxin preparations.

2 Articles were systematically collected and evaluated for scientific quality using pre-defined methodological criteria and then independently analysed for validity.

3 We found 105 publications exploring the effects of SAD preparations in toxicological systems.

4 The quality of evidence in these studies was low with only 43% achieving one half of the maximum possible quality score and only 31 % reported in a fashion that permitted reevaluation of the data.

5 Very few studies were independently replicated using comparable models.

6 Among the high quality studies, positive effects were reported 50% more often than negative effects.

7 Four of 5 outcomes meeting quality and comparability criteria for meta-analysis showed positive effects from SAD preparations.

8 Average percent protection over controls in these preparations was 19.7 (95%Cl 6.2-33.2).

9 Further research with special attention to methodological detail and independent replicafion should be done.
The Climate and the Occurrence of Carbon Monoxide Poisoning in Taiwan
Authors: Hung Dong-Zong , Deng Jou-Fang , Yang Chen-Chieh , Jen Li-Yu
Published: December 2008

Taiwan is an island situated in the subtropics. The lowest average temperature is around 15°C (59°F) during winter). Despite the mild climate, carbon monoxide intoxication still occurs frequently, especially during the winter. We studied which meteorological factor(s) affected the occurrence of carbon monoxide poisoning in Taiwan. Retrospective data over a period from December 1, 1986, to December 31, 1991, from patients who reported with carbon monoxide poisoning to the Poison Control Center, together with meteorological data were analysed. We found that a lower daily average temperature, especially while a special regional circulation pattern, called a 'cold front' or 'cold surge' (during winter) covers the Taiwan area, is strongly related to the occurrence of CO poisoning.