bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between dose in vivo of ethylene oxide and exposure to ethene studied in exposed workers
Authors: Granath F. , Rohlén O. , Göransson C. , Hansson L. , Magnusson A-L. , Törnqvist M.
Published: December 2008

1 In vivo doses of ethylene oxide, arising from ethene exposure, in plastic industry workers were estimated through hemoglobin adducts. The ethene exposure was assessed through person-worn monitors. The metabolic conversion of ethene to ethylene oxide was estimated from the exposure dose/ in vivo dose ratio.

2 Two studies were done: In the first study hemoglobin adducts were determined in samples collected on one occasion in exposed groups and exposure doses were estimated by using exposure data from the hygienic surveillance program. The second study applies a newly developed study design with repeated blood sampling in a few persons combined with a complete personal exposure monitoring during the study period. This makes it possible to relate adduct formation with individual short-time exposure doses, which in theory should overcome the problems with exposure history dependence of the adduct level in a single blood sample. The results of the second study shows that it is possible, through the proposed method, to utilize occupational exposure situations for this kind of studies even if the exposure pattern is irregular and highly variable. Both studies show a metabolic conversion of ethene to ethylene oxide of only 0.5%, which is unexpectedly low.

3 The cancer risk associated with the ethene exposure in the highly exposed group (3.6 p.p.m. 40 h/week) is estimated by applying the radiation-dose-equivalence approach. The result of this evaluation leads to a risk corresponding to a radiation dose of 4 mSv/year which is about a factor 3 below the current dose limit for radiological work recommended by ICRP.
Changes in cholinesterase activities after daunorubicin administration to rabbits
Authors: Geršl V. , Bajgar J. , Krs O. , Hrdina R. , Palička V. , Mazurová Y.
Published: December 2008

1 Acetyl- and butyrylcholinesterase (AChE, BuChE) activities were studied in rabbits with experimentally induced daunorubicin cardiomyopathy.

2 A significant decrease of the plasma BuChE in the daunorubicin group was observed.

3 In the daunorubicin group, AChE activity in the heart was significantly decreased only in the interventricu lar septum.

4 BuChE activity was significantly decreased in the cardiac septum and ventricles and in the liver following daunorubicin treatment.

5 Changes in cholinesterase activities are probably caused by an effect of daunorubicin oon protein synthesis during the development of certain types of cardiomyopathy.
Toxicity following accidental ingestion of Aconitum containing Chinese remedy
Authors: Kolev ST , Leman P. , Kite GC , Stevenson PC , Shaw D. , Murray Vsg
Published: December 2008

Various species of Aconitum are commonly used in traditional Chinese medicine. These plants are known to contain highly potent cardiotoxins. A 22 year old Chinese male accidentally ingested a herbal liniment prepared from Aconitum with near fatal results. His ventricular tachyarrhythmias responded to standard treatment in cluding the use of i.v. magnesium.
Pulmonary aspiration following Dettol poisoning: the scope for prevention
Authors: Chan Thomas YK , Critchley Julian AJH
Published: December 2008

1 After ingestion, Dettol liquid (4.8% chloroxylenol, pine oil, isopropyl, alcohol), a common household disin fectant, can cause central nervous system depression and corrosion of the oral mucosa, larynx and the gastrointestinal tract. The main risk from Dettol poisoning is pulmonary aspiration, leading to pneu monia, adult respiratory distress syndrome (ARDS) and/or sudden cardiorespiratory arrest.

2 To determine to what extent pulmonary aspiration in Dettol poisoning could be prevented, 13 patients treated in a general teaching hospital in Hong Kong were studied. Their clinical details were compared with those of control Dettol poisoning cases without pulmonary aspiration in order to identify possible risk factors for this complication.

3 At presentation, evidence of pulmonary aspiration was present in eight of the 13 patients prior to gastric emptying, but the use of gastric lavage without adequate protection of the airways could have aggravated the problem in three. In two other patients, evidence of aspiration was only present after gastric lavage was performed. The consequences of pulmon ary aspiration were pneumonia ( n=10), ARDS ( n=2), acute exacerbation of asthma or chronic obstructive airway disease (n=2) and sudden cardiorespiratory arrest ( n=1). Three patients with aspiration pneumo nia ( n=2), ARDS ( n=1) and/or sudden cardiorespira tory arrest ( n=1) died.

4 Compared with the controls, the median amount of Dettol ingested was considerably larger (400 vs 150 ml), vomiting (100% vs 72.6%) and drowsiness/ confusion (69.2% vs 19.4%) occurred more often.

5 Amongst the 13 patients with Dettol poisoning and pulmonary aspiration, gastric lavage using the naso gastric tube technique without adequate production of the airways had been responsible for the occurrence or worsening of aspiration in two and three patients, respectively. Thus, gastric lavage particularly when using a nasogastric tube appeared to carry more harm than benefits in patients with Dettol poisoning. If the procedure is considered necessary, say because of the concomitant ingestion of the other poisons, the air ways must first be well protected and the orophar yngeal aspiration and lavage technique using a wide bore Jacques tube is recommended.

6 Comparison with a control group has identified other risk factors for pulmonary aspiration: the amount of Dettol ingested, the occurrence of vomiting, drowsi ness or confusion.
Factors affecting hospital admission and length of stay of poisoned patients in the North East of England
Authors: Thomas Shl , Lewis S. , Bevan L. , Bhattacharyya S. , Bramble MG , Chew K. , Connolly J. , Dorani B. , Han KH , Horner JE , Rodgers A. , Sen B. , Tesfayohannes B. , Wynne H. , Bateman DN
Published: December 2008

1 Poisoning is a common reason for presentation to hospital and hospital admission but there is no agreed policy for managing these patients. This study exam ined the management of patients presenting with poisoning and the factors affecting the probability of hospital admission and prolonged stay.

2 Data on all cases of poisoning presenting to six Accident and Emergency departments in the North East of England over 12 weeks in 1994 was collected prospectively from A&E notes. Length of stay and outcome were recorded from hospital computer records.

3 Overall, 73% of patients were admitted to a medical ward. Probability of admission was not independently affected by age or gender but was increased in those with intentional poisoning (Odds Ratio (OR) 3.3 [95% CI 1.8, 6.1]), a history of self harm (OR 1.7, [1.0, 2.9]) or potentially hazardous poisoning (OR 3.7 [2.1, 6.6]). There were significant variations between hospitals (50 - 80%) which could not be attributed to case mix.

4 Prolonged stay ( > 2 nights) was more common in patients over 65 years (OR 6.8 [2.9, 16.1]), those with intentional poisoning (OR 2.7 [1.1, 6.6]) and those with potentially hazardous poisoning (OR 2.6 [1.4, 4.9]). Mean hospital stay was 1.5 days and varied signifi cantly between hospitals from 0.8 to 2.1 days and this was independent of case mix.

5 There are appreciable variations in the management of poisoning between hospitals which are not explained by patient characteristics. Savings would occur if rates of admission and duration of stay were reduced by those hospitals where admission is more frequent or hospital stay is longer. However, the impact of this on long term morbidity is unknown.
Airway epithelial damage induced by sulfur mustard in uinea pigs, effects of glucocorticoids
Authors: Calvet JH , Coste A. , Levame M. , Harf A. , Macquin-Mavier I. , Escudier E.
Published: December 2008

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a signifi cant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclu sion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observa tions and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.
Effects of multiple doses of organophosphates on evoked potentials in mouse diaphragm
Authors: Kelly Sean S , de Blaquière Gail E , Williams Faith M , Blain Peter G
Published: December 2008

1 Male albino mice were injected s.c. with an organopho sphate (mipafox, ecothiopate or paraoxon). Treat ments were either a single injection or multiple daily injections with lower doses for 5 or 8 days. At 3 h after injection the activity of brain and diaphragm acet ylcholinesterase and of brain neuropathy target esterase (NTE) was measured. Also measured in the diaphragm at 3 h post dose was the duration of spontaneous miniature endplate potentials (eMEPPs), recorded extracellularly.

2 At 7 and 28 days after dosing action potentials and evoked endplate potentials, produced by stimulating the phrenic nerve at 30 Hz, were recorded in diaphragm muscle. The amplitudes, time-course and latencies of these potentials were measured and the variability of latencies (jitter) was calculated.

3 Single doses of mipafox (20 mg/kg), ecothiopate (0.192 mg/kg) or paraoxon (0.415 mg/kg) in the mouse produced ca. 70% inhibition of diaphragm acetylcho linesterase at 3 h after dosing. All three OPs produced a prolongation of the half-decay times of eMEPPs.

4 All three OPs in the above single doses produced increased muscle action potential (postjunctional) jitter but only mipafox produced an increase in endplate potential (prejunctional) jitter. Mipafox in a slightly reduced single dose (17.5 mg/kg) had no effect on prejunctional or postjunctional jitter.

5 Multiple dosing with mipafox (8 mg/kg daily for 5 days) increased both postjunctional and prejunctional jitter at both 7 and 28 days after the end of dosing. After multiple dosing with mipafox (5 mg/kg daily for 5 days) postjunctional (but not prejunctional) jitter was increased. Multiple doses of paraoxon (0.166 mg/kg daily for 5 days) or ecothiopate (0.76 mg/kg daily for 5 days) increased prejunctional and postjunctional jitter.

6 Depending on the dosing regime, all three OPs tested were capable of increasing both prejunctional and postjunctional jitter. Neither ecothiopate nor paraox on inhibited NTE, so this prejunctional effect is not likely to be related to 'classical' OP-induced delayed neuropathy. The prejunctional effects may be related to long-term inhibition of acetylcholinesterase and the triggering mechanism for increase in prejunctional jitter may involve a relationship between the inhibi tion of acetylcholinesterase and the time for which it is inhibited. The differences between the time-courses of increases in prejunctional and postjunctional jitter and the differential effects of the different multiple dosing regimes indicate that it is likely that the triggering relationship between enzyme inhibition and time is different for prejunctional and postjunc tional effects.
Evidence of crack use by anhydroecgonine methylester identification
Authors: Kintz Pascal , Sengler Catherine , Cirimele Vincent , Mangin Patrice
Published: December 2008

A method using gas chromatography coupled to mass spectrometry for the determination of cocaine (COC) pyrolysis product, anhydroecgonine methylester (AEME), in plasma, saliva, urine, sweat and hair is described. The same procedure allows the simultaneous determination of COC, benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE). After suitable sample preparation (desorption of the sweat patch, acid hydrolysis of the hair) the target drugs were extracted using a 3-steps liquid- liquid extraction (pH 8.4) in presence of deuterated internal standards in chloroform-isopropanol- n-heptane (50 : 17 : 33, v/v). Derivatization was achieved using BSTFA+1% TMCS. Ions for AEME monitoring were m/z 82,166,152 and 181. Artifact formation from COC or EME of AEME during the injection was less than 0.5%. AEME was never detected in blood sample although the corresponding urine tested positive. Urine concentra tions, in about 90 positive AEME samples, were in the range 5 to 1477 ng/ml. In one case of crack overdose, AEME in sweat was 53 ng/patch with a COC concentration of 1231 ng/patch. AEME in saliva ranged from 5 to 18 ng/ml in the same case. Finally, AEME was identified in 32 hair specimens of crack abusers including fetal hair, with concentrations in the range 0.20 to 21.56 ng/mg. These results suggest that AEME can be a useful marker for the detection of COC smoking in clinical and forensic cases.
Effect of repeated treatment with pyridostigmine on acetylcholinesterase in mouse muscles
Authors: Lintern MC , Smith ME , Ferry CB
Published: December 2008

1 Pyridostigmine bromide was administered subcuta neously (0.4 μmoles/kg) in mice twice a day for 3 weeks. The activities of the predominant (G1, G4 and A12) molecular forms of acetylcholinesterase were determined in diaphragm, extensor digitorum longus (EDL) and soleus muscles.

2 After the treatment the G4 and A12 forms were reduced in diaphragm, but increased in EDL and soleus. One week later all forms were elevated in all three muscles. At 2 weeks the activity had returned to normal in diaphragm but not in EDL and soleus.

3 A single dose of pyridostigmine was administered in mice which had been pretreated for 3 weeks and left untreated for 2 weeks, and in control mice.

4 In the controls there was no significant effect on the enzyme activities in diaphragm up to 5 days, but there were decreases in EDL, and increases in soleus. In the pretreated group all three forms were increased in diaphragm, especially the A12 form. In soleus and EDL there was a prolonged decrease in all forms, although in the soleus the A12 activity remained above normal.

5 Repeated treatment with pyridostigmine caused de layed changes in functional acetylcholinesterase. Furthermore the treatment had altered the sensitivity of the muscles to the drug.
Epidemiology of poisoning in the New Territories South of Hong Kong
Authors: Chan Thomas YK , Chan Albert YW , Pang CW
Published: December 2008

Little is known about the incidence and pattern of poisonings in Hong Kong. Hence, adults (subjects aged ≥ 15 years) and children (subjects aged ≤ 14 years) hospitalized in the Princess Margaret Hospital in 1994 with ICD codes of 960-977 (medicinal poisonings) or 980 - 989 (non-medicinal poisonings) were studied. This is the main general hospital with a 24-hour emergency department for the 0.68 million people living in the New Territories South. Sex and age specific rates per 100 000 population were calculated. The incidence of poisoning in 1994 was 113.5/100 000. The incidence was higher in males than in females (130.0 vs 96.4/100 000). Poisoning was more common in adults than in children (128.8 vs 44.9/100 000). Subjects with medicinal poisonings were predominantly young females and hypnotics/sedatives were the main agents involved. In contrast, males aged 35-64 years predominated in non-medicinal poisonings, which were mostly related to alcohol. In children, medicinal poisonings were more common than non- medicinal poisonings (24.9 vs 20.2/100 000). All of the nine deaths were adults.
No linkage of the cytochrome P-450IIE1 (CYP2E1) C1/C2 polymorphism to schizophrenia
Authors: Iwahashi K. , Nakamura K. , Furukawa A. , Okuyama E. , Miyatake R. , Ichikawa Y. , Suwaki H.
Published: December 2008

We investigated, using PCR-SSCP analysis, the relation ship between schizophrenia and the polymorphism of d- benzphetamine N-demethylase (cytochrome P-450j or CYP2E1), which metabolizes psychotropic substances such as d-benzphetamine and alcohols. Among 41 patients with schizophrenia, no statistically significant change in the frequency of the mutant (C2) allele relative to in controls was found, and no novel structural mutation in the CYP2E1 gene, which would be expected to alter the CYP2E1 protein, was found. This could be explained by no linkage of the CYP2E1 gene (mutations in the exon 1- 9, and C1/C2 polymorphism) to schizophrenia.
Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats
Authors: Lailey Alison F
Published: December 2008

1 Perfluoroisobutene, a pyrolysis product of polytetra fluoroethene may cause pulmonary oedema and death when inhaled. Oral N-acetylcysteine has shown protection against inhalation of perfluoroisobutene and in this study we have tried to elucidate the mechanism by which protection is mediated.

2 Protection against the lethal effects of inhaled per fluoroisobutene has been shown when N-acetylcys teine has been orally administered 4, 6 or 8 h before gas exposure.

3 Plasma levels of cysteine, glutathione and N-acetylcys teine were increased for up to 7 h following oral administration of Nac.

4 N-acetylcysteine was not detected in the bronchio alveolar lavage fluid following oral administration.

5 Duration of protection in vivo has been related to the duration of increased thiol levels in the plasma.
Presence of methenamine/glutathione mixtures reduces the cytotoxic effect of sulphur mustard on cultured SVK-14 human keratinocytes in vitro
Authors: Smith CN , Lindsay CD , Upshall DG
Published: December 2008

1 The basal epidermal keratinocytes of the skin are a main target for the vesicating agent, sulphur mustard (SM). A human keratinocyte cell line (SVK-14) has been used to model the effects of SM on the basal epidermal keratinocytes and subsequently to test the efficacy of potential prophylactic compounds in reducing the SM-induced cytotoxicity.

2 The cultures were pretreated with mixtures of methe namine (HMT) and glutathione (GSH) for 1 h prior to exposure to 10 μM SM. The viability of the cultures was then assessed using neutral red (NR) dye uptake and crystal violet DNA staining assays at 24 h intervals post exposure.

3 Pretreatment led to a 1.9 fold increase in culture viability (NR assay) compared to those exposed to SM only, and a 2.3 fold increase in cell number (crystal violet assay). Photomicrography showed that pre treatment preserved the morphology of the cultured cells and maintained their mitotic activity whereas those exposed to SM only show non-proliterative cultures with extensive cellular damage.

4 The results of this study show that it is possible to protect mitotically active cultures from the effects of SM, however the measures must be in place prior to SM exposure.
Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat
Authors: Sadani Geeta R , Soman Chitralekha S , Deodhar Kedar K , Nadkarni Ganeshsunder D
Published: December 2008

1 Ricin is known to have diverse effects on the cells of different organs like liver, kidney, pancreas, intestines and parathyroid.

2 Acute decrease in serum thyroid hormone levels 24 h after ricin administration (1.5 μg/100 g) led us to suspect the toxic action of ricin on the thyroid.

3 We monitored the lipid peroxidation (LP) and anti oxidant status of the thyroid tissue to determine the role, if any, played by reactive oxygen species (ROS) in this pathology.

4 An increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease in catalase

points to the imbalance in the antioxidant defence involving hydrogen peroxide and its univalent reduc tion product, the hydroxyl radical.

5 Thyroid histopathology shows destruction of thyroid follicles and necrosis, which may be due to ROS and may partly explain the 50% reduction in circulating thyroid hormones seen after ricin administration.
Evaluating chemical risks: results of a survey of the British Toxicology Society
Authors: Slovic Paul , Malmfors Torbjörn , Mertz CK , Neil Nancy , Purchase Iain FH
Published: December 2008

1 Members of the British Toxicology Society partici pated in a survey to determine their attitudes, beliefs, and perceptions regarding risks from chemicals. Similar surveys had previously been conducted with toxicologists and members of the general public in the United States and Canada. Data from 312 completed questionnaires were analyzed.

2 In general, the British toxicologists judged risks to be quite low for most hazards, with the exception of cigarette smoking and asbestos. They tended to have quite favorable attitudes toward the use of chemicals and were confident about the adequacy of chemical regulations.

3 As in previous studies of toxicologists, women expressed higher perceptions of risk than did men and had consistently stronger anti-chemical attitudes.

4 Toxicologists working in industry had more favorable attitudes towards chemicals and their use than did those working in academic settings.

5 When asked to evaluate technical summaries of various animal studies there was considerable dis agreement among the respondents about the toxicity of the chemicals involved.

6 In general, British toxicologists were equivocal about the reliability of animal studies in predicting human effects (particularly carcinogenicity) probably be cause of the belief that animal studies overestimate risk. However, they were rather confident that human health risks could be assessed reasonably accurately.
Effects of oxygen pressure and medium volume on the toxicity of paraquat in rat and human type II pneumocytes
Authors: Hoet Peter HM , Demedts Maurits , Nemery Benoit
Published: December 2008

The herbicide, paraquat is highly toxic for mammals, with the lungs being the main target organ, because of the active accumulation of the compound in this organ. The cellular toxicity of paraquat has been shown to be an O2-driven process and hyperoxia is known to increase the lethality of paraquat. In this study we have examined the effect of various O2 concentrations on the toxicity of paraquat in rat and human type II pneumocytes in culture, and we have tested whether the thickness of the liquid layer above the cells would influence the toxicity of paraquat. Type II pneumocytes were isolated from rat or human lung tissue using trypsin digestion, Percoll density gradient centrifu gation and differential attachment. Adherent cells (day 2) were incubated for 20 h in different volumes of culture medium (thickness of liquid layer), whether or not in the presence of paraquat, in the presence of different O2 tensions. The viability of the cells was assessed by the release of LDH in the culture medium. In both rat and human type II pneumocytes the toxicity of paraquat was independent of the thickness of the liquid layer (2.5 to 10 mm height). The toxicity of paraquat in rat type II pneumocytes decreased from a TC50 value of 28 μM paraquat at 21% O2 to 107 μM at 10% O2 and increased to 12 μM and 8 μM at 60% and 85% O2, respectively. For human type II pneumocytes the TC50 values were 7 μM; 25 μM and > 1000 μM paraquat at 60%, 21% and 10% O2, respectively. In this study we have shown that the diffusion of O2 through a liquid layer does not limit the toxicity of paraquat and that, as in vivo, increasing O2 partial pressure enhances the toxicity of paraquat.
Effects of high-level exposure to lead on NK cell activity and T-lymphocyte functions in workers
Authors: Yücesoy Berran , Turhan Aslihan , Mirshahidi Saied , Üre Murat , Imir Turgut , Karakaya Asuman
Published: December 2008

1 NK and T cell functions were measured in peripheral blood lymphocytes of workers occupationally exposed to lead.

2 No differences were found in these functions even in those workers with higher levels of blood and urine lead and urinary δ-ALA than the currently accepted biological limit values as compared to controls.

3 We conclude that high chronic exposure to lead is not associated with an impairment or either T- or NK cell functions in man.
Defective neutrophil function in workers occupationally exposed to hexachlorobenzene
Authors: Queiroz Mls , Bincoletto C. , Perlingeiro Rcr , Souza CA , Toledo H.
Published: December 2008

In this work we have studied the respiratory burst and chemotaxis of polymorphonuclear leukocytes from 51 workers exposed to chlorinated compounds, which were compared with those of non-exposed, age- and sex- matched invididuals. These two neutrophil functions were significantly reduced as compared to controls. No correlation was observed between the length of exposure, hexachlorobenzene (HCB) blood concentrations and neu trophil chemotaxis or the extent of nitroblue tetrazolium reduction.
Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer
Authors: Harrison DJ , Cantlay AM , Rae F. , Lamb D. , Smith Cad
Published: December 2008

1 Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been associated with a number of apparently unrelated cancers, including lung cancer. Emphysema is a common lung disease often found concomitant with lung cancer. Both emphysema and lung cancer may result from chemical and oxidative damage caused by reactive species present in cigarette smoke or released from neutrophils recruited follow ing cigarette smoke induced injury. GSTM1 may protect against such damage through detoxification of cigarette smoke components. Polymorphism of this gene may thus influence susceptibility not just to lung cancer, but to other forms of lung disease.

2 Resection specimens from a group of 168 lung cancer patients were assessed for the presence of macro scopic centriacinar and panacinar emphysema. DNA was extracted from archival material and genotyped for the GSTM1 polymorphism using the polymerase chain reaction. A control group of 384 anonymous blood donations was used to determine the frequency of the GSTM1 gene deletion in a random control population. Reverse transcription on lung tissue was performed to investigate mRNA expression of GSTM1 and GSTM4.

3 In 57 lung cancer cases with no emphysema there was no association with homozygous deletion of the GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111 patients with emphysema and lung cancer there was an increase in the frequency of deletion (65%, P=0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases there was evidence of both centriacinar and panacinar emphy sema. The frequency of GSTM1 deletion was 70% (Odds ratio 2.11, 0.97 - 3.25). Both GSTM1 and GSTM4 mRNAs were expressed in lung tissue.

4 These findings suggest that GSTM1 has a general but rather small protective effect against toxicological injury in the lung which is not specific to cancer. This is of relevance in considering the health effects of exposure to a wide range of reactive chemicals in the environment.
Kinetic analysis of the intestinal iron absorption process in situ. The potential of vascularly autoperfused intestinal loops
Authors: Hunder G. , Osterloh K. , Schümann K.
Published: December 2008

1 Blood sampling from mesenteric venules during absorption in situ is a useful tool to analyse intestinal absorption kinetics and prehepatic metabolism in different sections of the rat small intestine. By use of a micromanipulator, the method can be applied to the duodenum. This part of the small intestine shows the strongest adaptation of non-haem iron absorption to the demand for iron.

2 Iron absorption kinetics was linear in duodenal and jejunal segments. In iron-deficient animals, intestinal iron absorption capacity was increased in the duode num, while simultaneously determined galactose absorption showed no change.

3 In situ perfusion and cannulation of mesenteric venules in duodenal segments are described. The use of a micromanipulator permits varying the blood volume collected by changing the vertical angle between the cannula and the mesenteric vessel.

4 Intestinal iron absorption rates remained close to constant when blood flow rates were varied by a factor of about ten. Plasma concentrations of absorbed iron vs mesenteric blood flow rates followed a hyperbolic function, as the plasma concentration of absorbed iron in mesenteric venules increased to the same extent as the blood flow decreased.

5 As the plasma transferrin concentration did not change over the experimental period, the concentra tion of absorbed iron in the mesenteric plasma exceeded the iron-binding capacity of plasma trans ferrin at low blood flow rates. This observation shows that enhancement of intestinal iron absorption does not require a corresponding increase in plasma iron- binding capacity in the intestinal tissue.

6 Vascularly perfused gut loops were also used to measure prehepatic metabolism, which may influence organotropism of carcinogenic metabolites. Therefore, this type of preparation is likely to find a variety of toxicological applications.
Influence of solubility and permeant size on absorption and metabolism of xenobiotics in rabbit skin
Authors: Bast Gabriele E
Published: December 2008

1 In order to obtain an understanding of the risks associated with dermal uptake of xenobiotics it is necessary to investigate the principles governing percutaneous absorption and metabolism. The sin gle-pass perfused rabbit ear served as a convenient model for the simultaneous study of absorption and metabolism of a variety of substances.

We found:

2 When substances are applied in a lipophilic vehicle the permeation coefficient K P is notably decreased when the distribution coefficient (n-octanol/perfusion buffer (pH 7.4)) Poct. exceeds 2000. KP also decreases with increasing molecular weight.

3 Substances which are in the ionized state at pH 7.4 may have a higher permeation coefficient than would be expected from Poct. or by molecular weight.

4 The partition of a drug from the stratum corneum to the epidermal enzymes controls the extent of its metabo lism. However, substances with increased solubility at physiological pH are metabolized to a lesser extent than expected from their absorption rate.
Primary aromatic amines: their N-oxidative bioactivation
Authors: Hlavica P. , Golly I. , Lehnerer M. , Schulze J.
Published: December 2008

There exists a diversity of pathways in mammalian cells serving to activate primary aromatic amines.

1 N-Oxidative mixed-function turnover usually involves participation of the cytochrome P450 superfamily, while catalysis by the flavin-containing monooxy genases is restricted to a few amines capable of forming imine tautomers. Surprisingly, haemoglobin metabo lizes cytotoxic and carcinogenic arylamines via a monooxygenase-like mechanism, but peroxygenase activity is also operative.

2 In extrahepatic tissues that exhibit only a low level of monooxygenases, peroxidative transformations, as are brought about by prostaglandin H synthase, myeloperoxidase or lactoperoxidase, predominate in amine activation. Non-mammalian peroxidases fre quently used as model systems include horseradish peroxidase and chloroperoxidase.

3 Non-enzymatic, light-induced conversion of aromatic amines to free radical or N-oxy products proceeds either via direct photolysis of the nitrogenous com pounds or through attack by lipid-derived reactive intermediates generated during irradiation.

4 The interplay of the various tissue-specific processes of arylamine activation serves to explain differences in susceptibility toward the biological actions of primary aromatic amines.
Biomonitoring exposure to environmental tobacco smoke (ETS): A critical reappraisal
Authors: Scherer G. , Richter E.
Published: December 2008

1 The most frequently used biomarkers for exposure to environmental tobacco smoke (ETS) are cotinine and thiocyanate in body fluids, carboxyhaemoglobin in red blood cells (COHb) and carbon monoxide in the expired air. Although not ideal, cotinine in blood, saliva or urine is an established biomarker for ETS exposure within the past 1-3 days. Comparison with cotinine concentrations in cigarette smokers reveals that passive smokers take up less than 1/100 of the nicotine dose of smokers.

2 Biomonitoring data available for the ETS-related exposure to genotoxic substances comprise uptake of benzene, polycyclic aromatic hydrocarbons (PAH), aromatic amines, tobacco-specific nitrosamines (TSNA), electrophilic compounds giving rise to ur inary thioethers, mutagens causing urinary mutagenic activity and the formation of various DNA adducts. With the exception of TSNA, these biomarkers are related to chemicals occurring ubiquitously in the environment and in the food. As a consequence, the background levels in unexposed nonsmokers are high compared to the observed increases (if any) associated with ETS exposure.

3 Some markers of biological effects, which, by defini tion, are non-specific with regard to the underlying exposure, have also been investigated in relation to ETS exposure. These markers comprise cytogenetic effects, aryl hydrocarbon hydroxylase (AHH) induc tion, urinary hydroxyproline excretion and various factors indicative of cardiovascular risks. The avail able data suggest that passive smoking is associated with a small induction of placental AHH and also with effects on cardiovascular risk markers. The latter findings in particular may be confounded by other risk factors, which have been observed to be more frequent in passive smokers than in unexposed nonsmokers.
Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimer's Disease
Authors: Martin F. , Corrigan FM , Donard Ofx , Kelly J. , Besson Jao , Horrobin DF
Published: December 2008

As blood tin concentrations are elevated in Alzheimer's disease and as some low molecular weight organotin compounds are neurotoxic, we have attempted to detect organotins in brain in Alzheimer's Disease. First we measured the concentration of trimethyltin (TMT) in the brains of rats which had been exposed to memory- impairing concentrations of TMT and, as the method of linking hydride generation, cryogenic trapping, gas chromatographic separation and atomic absorption spec trophotometric detection permitted the measurements of organotin compounds when the total tin was greater than 0.2 nanograms, we applied these techniques to human brain tissue, some of which showed neuropathological evidence of Alzheimer's Disease. No low molecular weight organotin compounds were detected in the human brain tissue, but it is possible that tin may be complexed with large organic molecules, the hydrides of which would not be volatile, but which could be identified by liquid chromatography.
Chelation in metal intoxication LI: Efficacy of amphipathic dithiocarbamates in mobilization of lead in the rat
Authors: Tandon SK , Singh S. , Prasad S.
Published: December 2008

N-benzyl-D-glucamine dithiocarbamate (BG.DTC) and its analog, N-(4-methoxybenzyl)-D-glucamine dithiocarba mate (MeO-BG.DTC) which are effective chelators of cadmium were investigated for their efficacy to induce excretion of lead, to reduce tissue burden of lead and to reverse certain lead sensitive biochemical alterations in lead pre-exposed rats. These were quite effective in reducing hepatic and renal but not brain lead levels as reflected by the enhanced urinary and fecal excretion of lead and in partially restoring lead inhibited blood delta- aminolevulinic acid dehydratase activity. The introduc tion of a methoxy group at para-position of benzyl ring, unlike in case of cadmium, did not improve the lead chelating ability of the compound. The treatment with BG.DTC and MeO-BG. DTC caused depletion of endogen ous essential elements such as zinc, copper and calcium as evidenced by their enhanced excretion and decreased tissue contents which were more marked in animals treated with the latter.
Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats
Authors: Kassa J. , Fusek J.
Published: December 2008

1 The effect of pharmacological pretreatment (pyridos tigmine, benactyzine and trihexyphenidyle), desig nated Panpal, and antidotal treatment (the oxime HI- 6 plus benactyzine) in soman poisoning was investi gated in a rat model with on-line monitoring of respiratory and circulatory parameters.

2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activ ity in diaphragm and various brain parts.

3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acet ylcholinesterase activity in all brain parts studied.

4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreat ment or antidotal treatment alone.

5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman- poisoned rats without significant reactivation of brain acetylcholinesterase.
Environmental exposure to polycyclic aromatic hydrocarbons in Czech Republic
Authors: Vyskocil Adolf , Fiala Zdenek , Fialova Dana , Krajak Vladimir , Viau Claude
Published: December 2008

1 Objectives of this study were (1) to compare concentra tions of individual polycyclic aromatic hydrocarbons (PAH) in air of polluted and nonpolluted area of Czech Republic during winter and summer periods and (2) to verify if urinary 1-hydroxypyrene (1-OHP), as sup posed practical biological marker, permits the assess ment of spacial and temporal variations in environmental PAH exposure.

2 The study population consisted of three groups: (1) a group of 22 physical exercise students who regularly train outside, from the university situated in a polluted town, spending 14 days in winter and 14 days in summer in 'non-polluted' mountains; (2) a control group of 22 residents from the town and (3) a control group of 18 residents from the mountains.

3 The total PAH concentrations (sum of 13 individual PAH) were 19.3 and 104.6 ng/m3 in town and in mountains, respectively, during summer and 86.6 and 261 ng/m3 during winter.

4 Median 1-OHP levels ranged between 0.03 and 0.13 μmol/mol creatinine for controls and between 0.04 and 0.12 μmol/mol creatinine for students. No relationship was found between pyrene levels in air and group means of urinary 1-OHP. Our results show that other factors (probably PAH in food) contribute in masking air pollution influence on urinary 1-OHP levels in subjects non-occupationally exposed to PAH.
An unusual poisoning with the unusual pesticide amitraz
Authors: Jorens Philippe G , Zandijk Eric , Belmans Luc , Schepens Paul JC , Bossaert Leo L
Published: December 2008

Amitraz, 1,5 di-(2,4-dimethylphenyl)-3-methyl-1,3,5-tria za-penta-1,4-diene, a formamidine pesticide, is used worldwide. It causes side-effects in animals that resemble those caused by pure α2-adrenergic agonist drugs such as clonidine. Data on poisonings in humans are scanty. We report on a case of human poisoning with amitraz with typical signs of α2-adrenoreceptor stimulation.
Monoisopropylglutathione ester protects A549 cells from the cytotoxic effects of sulphur mustard
Authors: Lindsay Christopher D , Hambrook Joy L , Lailey Alison F
Published: December 2008

1 The A549 cell line was used to assess the toxicity of sulphur mustard (HD), using gentian violet (GV) and neutral red (NR) dyes as indicators of cell viability. It was found that exposure to concentrations in excess of 40 ?M HD resulted in a rapid onset of toxicity.

2 The ability of monoisopropylglutathione ester (MIPE) to protect A549 cells against the effects of a 100 ?M challenge dose ofHD was determined using the NR and GV assays. It was found that MIPE (8 mM) could protect cells against the effects ofHD though MIPE had to be present at the time of HD challenge. Cultures protected with MIPE were two times more viable than HD exposed cells 48 h after HD challenge when using the GV and NR assays to assess viability. Observations by phase contrast microscopy of NR and GV stained cultures confirmed these findings. Addition of MIPE after previously exposing the A549 cultures to HD (for up to 5 min) maintained cell viability at 72% compared to 37% for unprotected cultures, after which time viability fell significantly so that at 10 min there was no difference in viability between the MIPE treated and untreated cultures.

3 Pretreating A549 cultures with MIPE for 1 h followed by its removal prior to HD challenge did not maintain cell viability. Treatment of cultures with HD for 1 h followed by addition of MIPE did not maintain the viability of the cultures, thus the window within which it was possible for MIPE to rescue cell cultures from the effects of HD was of short duration.

4 High performance liquid chromatography was used to determine the biochemical basis of the actions of MIPE. It was found that whilst intracellular levels of cysteine were increased up to 40-fold following treatment of A549 cell cultures with MIPE, levels of reduced glutathione did not rise. The lack of protection seen in cultures pretreated with MIPE for 1 h prior to HD exposure suggests that raising intracellular cysteine levels was not an effective strategy for protecting cells from the effects of HD. The protection observed is probably due to extra cellular inactivation of HD by MIPE.
Vipera palaestinae snake envenomations: experience in children
Authors: Paret G. , Ben-Abraham R. , Ezra D. , Shrem D. , Eshel G. , Vardi A. , Winkler E. , Barzilay Z.
Published: December 2008

In Israel, Vipera palaestinae (V. palaestinae) is the most common venomous snake, accounting for 100 - 300 reported cases of envenomation every year. However, V. palaestinae snakebites in children have not been exten sively investigated. The demographic features, treatment and outcome of V. palaestinae envenomation in 37 children treated in two medical centers over a 9 year period were retrospectively reviewed. The victims age ranged from 2-18 years with a mean age of 8.9 years. Twenty-nine children were males and eight were females. Twenty-one patients resided in rural areas, and 16 children were living in urban areas. Twenty-three (63%) of the patients were bitten on the lower limb; Twelve (33%) on the upper limb, and two on the head or neck (4%). Using a grading scale of one to three from minimal to severe envenomation, 15 (40.5%), 15 (40.5%) and 7 (19%) patients had mild, moderate and severe envenomation, respec tively. Major complications of envenomation that were manifested after arrival consisted of compartment syn drome (two patients) and respiratory dysfunction (two patients).

Specific monovalent antiserum for the treatment of V. palaestinae bite was given to 16 children (43%) of whom, four patients were in the severe group, seven and five in the moderate and mild groups respectively. No patient suffered a significant infection, tissue loss, permanent disability or death. We conclude that early ICU admission along with close monitoring and antivenom therapy is important in reducing morbidity and mortality in children systemically envenomed by V. palaestinae.
Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats
Authors: Nagymajtényi L. , Schulz H. , Dési I.
Published: December 2008

1 Three consecutive generations of Wistar rats were orally treated by gavage with 3.5, 7.0 or 14.0 mg/kg cadmium (in form of cadmium chloride diluted in distilled water) over the period of pregnancy, lactation and 8 weeks after weaning.

2 Behavioural (open field behaviour) and electrophysio logical (spontaneous and evoked cortical activity, etc.) parameters of male rats from each generation were investigated at the age of 12 weeks.

3 The main behavioural outcomes were change in vertical exploration activity (rearing) and increased exploration of an open field centre. The spontaneous and evoked electrophysiological variables showed dose- and generation-dependent changes (increased frequencies in the electrocorticogram, lengthened latency and duration of evoked potentials, etc.) signalling a change in neural functions.

4 The data show that low-level, multigeneration expo sure to inorganic cadmium can affect functions of the nervous system. This suggests that cadmium exposed human populations may be at risk of developing nervous system disorders.
Effects of quercetin on drug metabolizing enzymes and oxidation of 2', 7-dichlorofluorescin in HepG2 cells
Authors: Musonda CA , Helsby N. , Chipman JK
Published: December 2008

1 The effects of quercetin on drug metabolising enzymes and oxygen radicals were studied in human HepG2 cells.

2 Cytotoxicity of quercetin in HepG2 cells was seen at 50 μM and above as evaluated by lactate dehydrogen ase (LDH) leakage, neutral red (NR) uptake, and 3-(4,5- dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bro mide (MTT) reduction.

3 Quercetin inhibited activity of human cytochrome P- 450 towards ethoxycoumarin and ethylresorufin at relatively low substrate concentrations (0.1 μM and above).

4 In comparison to induction by the positive control (β- naphthoflavone; 1.0 μM), quercetin did not signifi cantly induce the metabolism of ethoxycoumarin or glutathione-S-transferase (GST) protein or activity.

5 Response elements for human CYP1A1, GSTλa, xenobiotic response element (XRE), fos, HSP70, CRE, p53, NFκB and DNA damage (GADD) in HepG2 cells were not activated by quercetin.

6 Quercetin exhibited antioxidant activity in HepG2 cells as evidenced by its ability to inhibit the oxidation of the fluorochrome dichlorofluorescin.

7 The results indicate a range of potential beneficial effects of quercetin with respect to the influence on carcinogen-metabolising enzymes, scavenging of re active oxygen species and a lack of stress response in HepG2 cells.
Haemoperfusion treatment in pigs experimentally intoxicated by paraquat
Authors: Yang TS , Chang YL , Yen CK
Published: December 2008

1 Because of their similarity in renal morphology and physiology to humans, domestic pigs (gilts, 70 kg) were bolus treated by intramuscular injection of 74,17, and 6 mg kg-1and by oral loading (70 mg kg-1n=4) of paraquat. The concentration peak of plasma paraquat was reached at 1.5 - 2.5 h. Renal clearance of paraquat rose to its maximum at 5 - 6 h after intoxication and then sharply decreased indicating renal failure. All the intoxicated pigs died.

2 An additional 10 gilts were also orally treated with 70 mg kg-1paraquat but received haemoperfusion from 2 h post intoxication for either 2 h (n=6) or 6 h (n=4). The 2 h haemoperfusion resulted in a 5.1% toxin removal but failed to save any of six poisoned pigs. Prolonged 6 h haemoperfusion successfully rescued three out of four intoxicated pigs.

3 The plasma paraquat concentrations of the three surviving pigs were above 2 mg l-1at 10 h post intoxication. This level is not only similar to those of untreated animals that died later, but also well beyond the suggested limit for survival of poisoned patients.

4 Pigs proved to be a good animal model for studies in paraquat poisoning and/or haemoperfusion. It is also suggested that early haemoperfusion is effective in treating paraquat poisoning even in very severe cases due to its possible detoxicating effect in addition to toxin removal.