bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient particulate matter induces relaxation of rat aortic rings in vitro
Authors: Knaapen A M , den Hartog G J , Bast A , Borm P JA
Published: April 2003

Epidemiological studies have shown an association between ambient levels of particulate matter (PM) and increased mortality from cardiovascular diseases. However, the underlying mechanisms are still not clear. We hypothesised that PM, when translocated after inhalation, could affect vascular smooth muscle function. Therefore, total suspended particulate matter (TSP) was sampled and investigated for its ability to affect aortic muscle contraction. Both TSP and TSP supernatant (TSP-sup) induced a concentration-dependent relaxation of phenylephrine (PE)-precontracted aortic rings. Relaxation induced by 100 jg/ml TSP was 51.5 t 3.1% of total contraction. At 60 and 100 Hg/ ml, relaxation induced by TSP was significantly higher compared to TSP-sup. Ultrafine TiO2, used as a model to investigate the role of ultrafine particles, did not show an effect. Soluble iron, present in TSP suspensions, seems not to be involved, as chelating with deferoxamine did not affect TSP-induced relaxation. However, TSP effects were inhibited by Trolox, suggesting a role of oxidants. Nudation of aortic rings showed that effects of TSP were only partly endothelium-dependent, while preincubation with LNAME increased TSP-induced relaxation. From these data, we conclude that both the particle core and soluble components of TSP can affect the smooth muscle function, leading to changes in the vascular contractile response.
Activation of human neutrophils by chiordane: induction of superoxide production and phagocytosis but not chemotaxis or apoptosis
Authors: Gauthier M , Girard D
Published: April 2003

We have recently reported that human neutrophils are important targets of different xenobiotics, including chemicals of environmental concern. In the present study, we found that chlordane was not toxic for human neutrophils incubated for up to 24 h with concentrations ranging from 0.1 to 50 pg/nl. Chlordane was found to induce neutrophil superoxide production (Oz–) in a concentration–dependent fashion and its potency to induce this response was found to be similar to phorbol 12-myristate 13-acetate (PMA), a classical neutrophil agonist. The use of different transduction signal inhibitors (genistein, pertussis toxin, staurosporine, and calphostin C) indicates that, as for PMA, chlordane induces 02 production via protein kinase C (PKC). In this respect, staurosporine and calphostin C were found to inhibit chlordane–and PMAinduced 02 production by 65% and 72%, and by 83% and 85%o, respectively. Chlordane was also found to significantly enhance neutrophil phagocytosis of opsonized sheep red blood cells (SRBCs). Despite these effects, chlordane did not alter neutrophil apoptosis as assessed by cytology (Diff-Quick staining) and by flow cytometry (CD-16 expression). In addition, chlordane did notalterneutrophil chemotaxis (48–well Boyden chamber). Cells were, however, responsive as they were activated by the well–characterized interleukin (IL)–8 chemokine. We conclude that chlordane can activate 02 production by a PKC-dependent mechanism and induce phagocytosis without altering chemotaxis and apoptosis. Chlordane must be added to a growing list of environmental contaminants that share some pro–inflammatory properties.
Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress
Authors: Balkan J , Dogğru-Abbasoğlul S , Kanbaglil ö , Çevikbas U , Aykaç-Toker G , Uysal M
Published: April 2003

Thioacetamide (TAA) administration (0.3 g/l of tap water for a period of 3 months) to rats resulted in hepatic cirrhosis as assessed by biochemical and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA) and diene conjugates (DCs) and a decrease in the levels of glutathione (GSH), vitamin E, vitamin C and the activities of glutathione peroxidase (GSH-Px) in the liver of rats. Superoxide dismutase (SOD) activities were unchanged. Taurine (2% w/w, added to the chow diet) was administered together with TAA (0.3 g/l of drinking water) for 3 months. Taurine was found to decrease TAA-induced hepatic lipid peroxidation and to increase TAA-depleted vitamin E levels and GSH-Px activities. Histopathological findings also suggested that taurine has an inhibitive effect on TAA-induced hepatic cirrhosis. These results indicate that taurine treatment has a protective effect against TAAinduced liver cirrhosis by decreasing oxidative stress.
Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone
Authors: Beelen A P , Yeo K-TJ , Lewis L D
Published: April 2003

We report a patient who ingested a 2000-mg overdose of quetiapine fumarate (Seroquel3™5). Her maintenance medications also included risperidone, venlafaxine, topiramate, and clonazepam. On presentation, she was drowsy, but had no other significant CNS signs and no cardiac symptoms or abnormal physical signs. Approximately 2 h after the quetiapine ingestion, an electrocardiogram (ECG) showed normal sinus rhythm at 95 beats/min with a corrected QT (QTc) interval of 537 ms (upper limit of normal = 440 ms). Plasma quetiapine concentration at that time was 1800 ng/ml. Continuous ECG monitoring for the subsequent 18 h did not reveal any episode of ventricular tachycardia. A 12-lead ECG 18 h post-overdose was normal with a QTc interval of 401 ms and the corresponding plasma quetiapine concentra-tion was 160 ng/ml. She made an uneventful medical recovery from the toxic ingestion. This case suggests that when patients overdose on quetiapine while taking therapeutic doses of risperidone, such overdoses, even if not massive, can cause considerable QTc interval prolongation. We recommend that quetiapine overdose patients undergo continuous ECG monitoring for 12-18 h post-ingestion.
Dtermination of coumarin metabolism in Turkish population
Authors: Çok I , Kocabaş N Aygüin , Cholerton S , Karakayal A E , Şardaş S
Published: April 2003

Cytochrome P450 2A6 is an important human hepatic P450 which activates precarcinogens and oxidizes some drug constituents such as coumarin, halothane, and the major nicotine C-oxidase. Genetic polymorphism exists in the CYP2A6 gene. CYP2A6*1 (wild type)is responsible for the 7-hydroxylation of coumarin. The point mutation (T to A) in codon 160 leads to a single amino acid substitution (Leu to His) and the resulting protein, CYP2A*2 is unable to 7-hydroxylate coumarin. Gene conversion in exons 3, 6, and 8 between the CYP2A6 and the CYP2A7 genes creates another variant, CYP2A6*3. In this study, healthy male and female Turkish volunteers (n = 50) were administered 2 mg coumarin, and urine samples were analyzed for their content of the coumarin metabolite, 7-hydroxycoumarin (70HC), by high-performance liquid chromatography (HPLC). Genetic polymorphism for CYP2A6 was detected by using two-step polymerase chain reaction (PCR) to identify CYP2A6*1, CYP2A6*2, and CYP2A6*3 in 13 of these subjects. The percentage of the dose excreted of total 70HC in relation to CYP2A6 genotype and excretion of nicotine/cotinine was also evaluated to demonstrate the role of CYP2A6 in nicotine metabolism. The majority of Turkish subjects (68%) excreted less than 60% of the 2-mg dose as coumarin metabolite. The allelic frequencies were detected as 0.88 for CYP2A6*1 allele; 0.12 for CYP2A6*3 allele in 13 individuals. No heterozygous and homozygous individuals were identified for the CYP2A6*2 allelic variant. Phenotyping and genotyping for drug metabolizing enzymes are of great importance in studies correlating precarcinogen activation or drug metabolism to the CYP2A6 genotype in smoking behavior when populations are investigated.
The management of Elephant's Ear poisoning
Authors: Tagwireyi D , Ball D E
Published: April 2003

The Araceae family of plants is the major cause of symptomatic plant ingestions in some developed countries (Dieffenbachia and Philodendron) and in Zimbabwe (Elephant's Ear), especially in children. A retrospective case series was carried out to evaluate the management of poisoning due to Elephant's Ear at the largest referral hospital in Zimbabwe for the period January 1995-December 1999. The study revealed inappropriate use of antibiotics, atropine, and antihistamines in the treatment of Elephant's Ear poisoning. This article also reviews the management of poisoning due to the Araceae family of plants as exemplified by Elephant's Ear. There is a need to educate health care workers on the clinical management of Elephant's Ear poisoning especially in developing countries where there are limited resources.
Study of the toxicological effect of mitomycin C in mice: alteration on the biodistribution of radiopharmaceuticals used for renal eva uations
Authors: Gomes M L , de mattos D Mm , de souza freitas R , Bezerral R Jac , Bernardo-Filho M
Published: April 2003

Mitomycin C (MMC) has been used as a component of many chemotherapeutic regimens and some toxic effects of this substance have been reported. As it has been reported that the toxicological effect of a drug can alter the biodistribution of radiopharmaceuticals and because patients on chemotherapeutic treatment can be submitted to a nuclear medicine procedure, we investigated whether MMC could affect the uptake of various technetium - 99m (99mTc) radiopharmaceuticals used for renal evaluations. The purpose of this study was to suggest a model to evaluate the toxic effect of substances in specific organs. Three doses of MMC (0.45 mg) were administered to mice (N= 15). One hour after the last dose, 99mTc radiopharmaceuticals, 99mTc-diethylene-triaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA) or 99mTc-glucoheptonic acid (99mTc-GHA), with activity of 7.4 MBq, were also administered in the treated group and in the control group (N= 15). After another 0.5 h, the animals were sacrificed. The organs were isolated, the 99mTc radiopharmaceutical uptake in the organs quantified in a well counter and the percentages of radioactivity (%ATI) calculated. The results have shown that: (i) with 99mTc-DTPA, the%ATI increased in the pancreas, ovary, uterus, stomach, kidney, spleen, thymus, heart, lung, liver, thyroid and bone; (ii) with 99mTc-DMSA, the%YATI decreased in all the organs except for the brain; and (iii) with 99mTc-GHA, the%ATI increased in the liver and decreased in the stomach, thymus, heart and thyroid. The effects of this chemotherapeutic drug on the biodistribution of these radiopharmaceuticals were statistically significant (Wilcoxon test, p<0.05) and could be explained by the metabolization and/or therapeutic action of MMC. Studies with other radiopharmaceuticals are in progress.
Effect of dimethyl sulfoxide on gentamicin-induced nephrotoxicity in rats
Authors: Ali B H , Mousa H M
Published: April 2003

Nephrotoxicity of gentamicin (GM) has been suggested to be mediated by the generation of reduced oxygen metabolites. The present study investigated the possible protective role of the free radical scavenger dimethyl sulfoxide (DMSO) on some indices of GM nephrotoxicity in rats. The antibiotic was injected intramuscularly (i.m.) at a dose of loo mg/kg for six consecutive days, either with or without treatment with DMSO (12.5%, 25% or 50% in saline) at an intraperitoneal (i.p.) dose of 2 ml/kg 4 days before GM, and concomitantly with GM treatment thereafter. DMSO (25% in saline) was also given as above to rats treated with GM at i.m. doses of 25, 50 or 100 mg/kg for six consecutive days. GM caused dose-dependent significant increases in the concentrations of urea and creatinine in plasma, and in thiobarbituric acid reactive substances (TBARS) level in the kidney cortex and also caused significant decreases in the concentrations of reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In GM-treated rats, DMSO dose-dependently lowered the elevated plasma urea and creatinine concentrations, and the rise in cortical TBARS. It also restored the levels of GSH and SOD activity to near normal. DMSO (25%) was effective in completely preventing the development of signs of nephrotoxicity of G (50 mg/kg). Treatment of the rats with DMSO alone, at any of the above doses, did not alter significantly any of the renal or hepatic function tests studied, and did not appear to adversely affect the kidney or liver histology. However, the efficacy and safety of DMSO require further studies. It is suggested that DMSO has potential protective effect against GM nephrotoxicity in rats.
Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells
Authors: Cheng J-S , Wang J-L , Lo Y-K , Chou K-J , Lee K-C , Liu C-P , Chang H-T , Jan C-R
Published: April 2003

This study investigated the effect of the anti-anginal drug, fendiline, on intracellular free Ca2+ levels ([Ca2+]i)inHA/ 22 human hepatoma cells by using fura-2 as a fluorescent Ca2+ dye. Fendiline (1-100 μM) increased [Ca2+]i with an EC50 of 25 μM. Removal of extracellular Ca2+ reduced the [Ca2+]i signals by 51-5%. Fendiline (10 μM)-induced Ca2+release was abolished by pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with 2 μM 1-(6-((17β 3 methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H pyrrole-2,5-dione (U73122) did not alter 10 μM fendilineinducedCa2+ release.Severalothercalmodulinantagonists, such as phenoxybenzamine (100-200 μM), trifluoperazine (5-50 μM),andfluphenazine N-chloroethane(2-100 μM), hadno effect on[Ca2+]i. Together, it wasfound that fendiline increased [Ca2+]i in human hepatoma cells by discharging Ca2+ from the endoplasmic reticulum in an inositol 1,4,5 trisphosphate-independent manner and by inducing Ca2+entry. This effect of fendiline does not appear to be via antagonism of calmodulin.
Lipid peroxidation as a possible secondary mechanism of sterigmatocystin toxicity
Authors: Sivakumar V , Thanislass J , Niranjali S , Devaraj H
Published: April 2003

Sterigmatocystin (Stg), a major secondary metabolite of Aspergillus versicolor and A. nidulans, is the precursor of aflatoxin B1 In this study, male albino rats were treated with Stg-contaminated diet for 30 days, resulting in reduced levels of glutathione, ascorbic acid, and tocopherol. The activity of catalase in liver was reduced, whereas an increase in the activities of superoxide dismutase and glutathione peroxidase was observed. The levels of cytochrome P450, cytochrome b 5, cyto-chrome b 5 reductase, cytochrome c reductase, hydroxyl radical, and hydrogen peroxide formation significantly increased in the Stg-treated rat liver microsomes. Hepatic parenchymal cell injury, necrosis, and Kupffer cells proliferation were noticed in histological sections of liver from animals treated with Stg. Overall results suggest that generation of free radicals imposes depletion of antioxidants. This led to enhanced lipid peroxidation. The observed elevation of hepatic thiobarbituric acid reactive substances appears to originate mainly from the damaged Kupffer cells. As a result, elevated levels of serum marker enzymes were also observed.
Effect of spironolactone on cisplatininduced nephrotoxicity in rabbits
Authors: Ahmida M HS , Abdel-Gayoum A A , El-Fakhri M M
Published: April 2003

The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day 1), oral doses of spironolactone (20.0 mg kg 1) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P<0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+ cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spiro nolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spiro nolactone significantly (P<0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit.
Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: Prevention by superoxide dismutase+catalase and vitamins E and C
Authors: Anane R , Creppy E E
Published: April 2003

Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialde hyde (MDA) produced inside the cells. The MDA–thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts. Human & Experimental Toxicology (2001) 20, 477–481.
Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets
Authors: Ciaravino V , McCullough T , Dayan A D
Published: April 2003

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.
Effects of cadmium on gap junctional intercellular communication in WB-F344 rat liver epithelial cells
Authors: Jeong S-H , Cho M-H , Cho J-H
Published: April 2003

Cadmium has been associated with a number of tumors but its role in tumor promotion has not been elucidated clearly or the results obtained from various studies have been conflicting. This study was designed to investigate the effects of cadmium on the gap junctional intercellular communication (GJIC), number of gap junctions per cell, and cell proliferation in WB-F344 rat liver epithelial cells from the viewpoint of tumor promotion. GJIC was monitored by counting the cells stained with Lucifer yellow CH dye, using the scrape-loading and dye-transfer method. The numbers of gap junctions per cell were visually quantitated after an indirect immunostaining for gap junction protein using an antibody to connexin 43. Cell proliferation was assayed by direct counting of the living cells using the trypan blue dye exclusion method. In the time course study, cells treated with 200 μM CdCl2 showed rapid and nearly complete inhibition of GJIC (approximately 14% of the control) and a decrease in the number of gap junctions per cell (approximately 21% of the control) at 30 min, and the decrease continued up to 4 h without any changes in the cell viability. Treatment with CdCl2 7.4-200 μM) for 4 h resulted in the decrease of GJIC and gap junction numbers per cell in a dose-response pattern without changes in the cell viability. In the long-term (14 days) exposure studies at doses of 0.01-7.4 μM CdCl2, an increase in cell proliferation was observed at low doses of 0.03-2.5 μM CdCl2, with GJIC also decreasing. These data demonstrate that cadmium inhibits GJIC, reduces the number of gap junctions per cell, and induces cell proliferation while decreasing the function of the gap junction.
Captopril inhibits the pulmonary toxicity of paraquat in rats
Authors: Candan F , Alagözlü H
Published: April 2003

Paraquat (PQ) is a herbicide that is very toxic to all living organisms. It generates free radicals and leads to acute or chronic lung injury. Free radicals are often associated with fibrogenesis, which occurs in various disease states. The purpose of this study was to determine whether captopril prevents paraquat toxicity in lung tissue. Paraquat alone increased the level of lipid peroxidation (LPO) and the activity of superoxide dismutase (SOD) after 4, 12, 24 and 72 h of administration. Also, the level of hydroxyproline showed an increase after 24 h of paraquat administration. However, paraquat also decreased the level of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). Captopril (50 mg/kg i.p.) and paraquat were simultaneously injected (40 mg/kg i.p.), and the captopril injection 1 h after paraquat ameliorated the biochemical toxicity induced by paraquat. This was evidenced by a significant reduction in LPO and balancing the endogenous anti-oxidant capacity by normalizing the activities of SOD and GSH-Px and the GSH content in the lung tissue. Moreover, captopril injection prevented the increase of hydroxypro-line content as an index of lung fibrosis. From these results, the beneficial effects of captopril on paraquat toxicity appear to be through enhancement of the endogenous anti-oxidant system preventing the lung fibrosis.
Diepoxybutane and mitomycin C toxicity is associated with the induction of oxidative DNA damage in sea urchin embryos
Authors: Pagano G , Degan P , De Biase A , Iaccarino M , Warnau M
Published: April 2003

Diepoxybutane (DEB)-and mitomycin C (MMC)-associated toxicity was investigated in embryos from the sea urchin (SU) species Sphaerechinus granularis. DEB-and MMC-induced toxicity resulted in S. granularis embryos and larvae at concentrations ranging 10 5 to 10 4 M DEB, and 3 10 3International Atomic Energy Agency, Quai 6 to 3 10 5 M MMC, in terms of larval malformations, developmental arrest and mortality. The formation of DNA oxidative damage, 8-hydroxy-20-deoxyguanosine (8-OHdG) was measured in DEB-and in MMC-exposed embryos (at gastrula stage). A dose-dependent increase in 8-OHdG levels was observed that was significantly correlated with DEB-and MMC-induced developmental defects. The results lend further support to the body of evidence associating both DEB and MMC toxicity with oxidative stress, including DNA oxidative damage. Human & Experimental Toxicology (2001) 20, 651–655.
Human biokinetics of injected bismuth-207
Authors: Newton D , Talbot R J , Priest N D
Published: April 2003

A healthy male volunteer received an intravenous injection of 207Bi as citrate. Levels of the tracer in blood and in excretion samples, and its retention and distribution within the body, were investigated by appropriate radioactivity measurements. Levels in blood fell very rapidly, with only 1% of the injection remaining at 7 h and only ca. 0.1% at 18 days. There was rapid initial excretion, with 55% lost during the first 47 h, principally in urine; however, longer-term losses were much slower and 0.6% remained in the body at 924 days, when the contemporary rate of loss implied a half-life of 1.9 years. Integration of the retention pattern suggested that steady exposure to bismuth compounds could lead ultimately to a body content of 24 times the daily systemic uptake. The largest organ deposit was in the liver, which after 3 days contained ca. 60% of the contemporary whole body content, consistent with reports of hepatotoxicity. These findings differ markedly from the metabolic model for bismuth proposed by the International Commission on Radiological Protection, which envisages a terminal half-life in the body of only 5 days and kidney as the site of highest deposition.
Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats
Authors: Selmanoğlu G , Barlas N , Songür S , Koçskaya E A
Published: April 2003

Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.
Organochlorine pesticide residues in human milk in the United Kingdom 1997–8
Authors: Harris C A , O'Hagan S , Merson G HJ
Published: April 2003

1 The concentrations of a range of organochlorine pesticide residues have been determined in 168 samples of human milk collected between January 1997 and May 1998 in the UK. 2 Of the 18 residues sought, only p,p′-DTT, p,p′-DDE, dieldrin, HCB, β-HCH and γ-HCH were detected. 3 The continuing trend of a reduction in the concentrations of these pesticide residues in human milk samples and in the percentage of human milk samples containing residues was seen. 4 Correlations between the concentrations of p,p′-DDE, dieldrin, HCB, β-HCH and γ-HCH and age were seen. 5 When compared to studies carried out in Europe over a similar time period, residues in this present study were shown to occur at similar or lower concentrations.
Organotin compounds decrease in vitro survival, proliferation and differentiation of normal human B lymphocytes
Authors: De Santiago A , Aguilar-Santelises M
Published: April 2003

Organotin compounds (OTC) are organometallic compounds with vast industrial and agriculture applications that give rise to ubiquitous environmental contamination. OTC are immunotoxic, but most studies have been performed in rodents and almost exclusively focused on T cell immunity. Humans can be exposed to OTC by inhalation, absorption, and consumption of contaminated food and water. To analyse the effects of OTC in human immune tissue, we isolated B cells from tonsils and exposed them to five OTC at various concentrations, during in vitro culture. Non-stimulated B cells were killed by 100 nM of all tested OTC after 8 h in vitro culture, under sub-optimal conditions, except TET. OTC also decreased the proliferation of tonsillar B lymphocytes stimulated with Staphylococcus aureus Cowan 1 (SAC) and IL-2, when present at 100 nM and higher concentrations. IgM secretion was reduced in stimulated cell cultures exposed to 100 nM dibutyltin chloride (DBT). Accordingly, increased phosphatidylserine exposure demonstrated that 100 nM TPT and DBT induced B cells to die by apoptosis. These data indicate that human B cells are diminished in their capacity to survive, proliferate and differentiate in the presence of OTC in vitro.
Delayed transient loss of consciousness in acute carbon monoxide intoxication
Authors: Benaissa M L , Lapostolle F , Borron S W , Baud F J
Published: April 2003

In acute carbon monoxide intoxication the presence of altered consciousness, ranging from transient loss of consciousness to coma, represents a poor prognostic factor and modifies the approach to therapy. Transient loss of consciousness is, as a rule, contemporaneous to the exposure, generally occurring at the scene of the intoxication. We report an unusual case of delayed transient loss of consciousness, occurring in the absence of any other evident aetiology, in one member of an orchestra composed of 110 members after a mass carbon monoxide poisoning.
Human volunteer studies; a consumer products company view
Authors: Roggeband R , Scailteur V , Basketter D A
Published: April 2003

The term ‘contact dermatitis’ refers to a range of adverse effects whose causation is quite varied. Manufacturers of consumer products have an important responsibility to minimise the extent to which their products cause such skin reactions. In meeting this responsibility, use may be made of humans, e.g. in studies related to skin irritation, to try to ensure the highest possible safety standards are achieved. The purpose of this short review paper is to outline the principles that must be followed before initiating studies with human volunteers. In addition, these principles are considered in the context of European legislation on chemicals and preparations.
Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress
Authors: Ahmed S , Rahman A , Saleem M , Athar M , Sultana S
Published: April 2003

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 mmol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P50.05) and liver (**P50.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P50.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.
Detoxification of organophosphates by A-esterases in human serum
Authors: Sams C , Mason H J
Published: April 2003

1 In vitro detoxification of the organophosphate (OP) insecticides paraoxon, chlorpyrifos-oxon and malaoxon has been investigated in human serum.

2 Specific A-esterase activity to each OP substrate was measured in the serum of 100 individuals using established spectrophotometric methods for paraoxonase and chlorpyrifos-oxonase and a novel assay for malaoxonase activity.

3 Dose-effect inhibition of serum cholinesterase by the three OPs was measured in pooled human serum. Inhibition of calcium dependent A-esterases by addition of EDTA resulted in increased inhibition of cholinesterase at a given OP concentration.

4 Data from both the direct spectrophotometric measurement of A-esterase activity and inhibition of serum cholinesterase in the presence and absence of Aesterase activity indicated that human serum Aesterase catalysed detoxification of chlorpyrifosoxon4 paraoxon4 malaoxon. Our data also confirms the wide variation in potency to inhibit cholinesterase between the three OPs.

5 Malaoxonase activity in human serum does not appear to be polymorphic, however, there is large interindividual variation as has been previously found for other A-esterases.

6 This study has demonstrated two approaches to investigate the inter-individual variation towards specific OPs and the relative ability of human serum A-esterase to detoxify specific OP compounds.
Rapid lethal intoxication caused by the herbicide glyphosate-trimesium (Touchdown)
Authors: Sørensen F W , Gregersen M
Published: April 2003

Two cases of rapid lethal intoxication with the herbicide glyphosate-trimesium (Touchdown) are presented. A 6-year-old boy who accidentally ingested a mouthful of glyphosate-trimesium died within minutes. The same happened to a 34-year-old woman who intentionally ingested approximately 150 ml of glyphosate-trimesium. The post-mortem examination revealed gastric content and oedema of the mucus membranes of the airways, erosion of the mucus membranes of the gastrointestinal tract, pulmonary oedema, cerebral oedema, and dilated right atrium and ventricle of the heart. The speed of which death occurs is much more rapid than lethal intoxications with the herbicide glyphosate (isoprophylamine), also known as ‘Roundup’. It is suggested that the lethal mechanism between the two herbicides may be different. The component, trimethylsulfonium, of the glyphosatetrimesium may facilitate the absorption after oral ingestion. This difference can be crucial in the treatment of human intoxication. We propose that containers with glyphosate-trimesium must be labelled because of the apparent effect of lethal intoxication.
Effects of muscle relaxants on EEG, ABR and EMG in rabbits
Authors: Saito T , Yamamoto I , Huang X-L , Yukawa N , Osawa M , Takeichi S
Published: April 2003

The effects of baclofen and pancuronium bromide on evoked electromyogram (EMG), cortical electroencephalogram (EEG) and auditory brainstem responses (ABR) were studied in pentobarbital anesthetized normal rabbits. Evoked EMG was measured in the gastrocnemius muscle by electrical stimulation of the sciatic nerve. Intravenous injection of baclofen decreased EEG and arterial blood pressure and light reflex, however, it had no significant influence on EMG or ABR at doses of 10 and 20 mg/kg/h. Pancuronium bromide immediately inhibited respiration, decreased EEG and EMG, however, it had no significant influence on arterial blood pressure, ABR, or light reflex, at doses of 0.4 and 1.0 mg/kg/h in anesthetized rabbits. ABR waves were observed until just before cardiac arrest with both of the muscle relaxants. It is suggested that ABR are not influenced by central or peripheral muscle relaxants, or by pentobarbital.
Longterm treatment of psoriasis using fumaric acid preparations can be associated with severe proximal tubular damage
Authors: Raschka C , Koch H J
Published: April 2003

Fumaric acid preparations are used as longterm and effective treatment of psoriasis. Apart from gastrointestinal, dermatological and hematological side-effects, transient renal damage was observed during treatment with fumaric acid. The case of a 38 year old woman who was treated with fumaric acid (420 mg bid) for 5 years before she complained of fatigue and weakness. According to clinical laboratory she had developed severe proximal tubular damage. Hypophosphatemia, glycosuria and proteinuria persisted although medication was stopped immediately.
Passive smoking, sudden infant death syndrome (SIDS) and childhood infections
Authors: Dybing Erik , Sanner Tore
Published: April 2003

1 A number of cohort and case-control studies have shown clear, dose-related associations between maternal smoking and infant death. The strongest relationships were found when the mother smoked during pregnancy as well as postnatally. Maternal smoking during pregnancy increases the risk for SIDS in most studies, whereas it appears that maternal smoking only postnatally also leads to an increase in risk. In addition, smoking only by the father appears to increase the risk for SIDS, but this is not seen in all studies. 2 Exposure of children to environmental tobacco smoke (ETS) increases the risk of having night cough and respiratory infections (bronchitis, bronchiolitis, pneumonia), especially during the first 2 years of life. An increased risk is also seen in studies not distinguishing between upper and lower respiratory diagnoses. Longterm breastfeeding may have a protective effect on ETS-increased risk of lower respiratory tract illness. One study of older children reports that ETS combined with allergy increased the risk of acute respiratory tract infections above that due to ETS alone. 3 The number of new episodes and duration of otitis media with effusion in young children is positively correlated with ETS exposure. Especially infants with lower birth weights had a high risk of recurrent otitis media during the first year of life when the mother was a heavy smoker. 4 Passive smoking has been reported as a risk factor in meningococcal disease and tuberculosis in young children.
Passive smoke exposure in infants and children with respiratory tract diseases
Authors: Kohler Elke , Sollichl Veronika , Schuster Renate , Thal Wilhelm
Published: April 2003

1 The adverse effect of passive smoke exposure on the respiratory tract, particularly in infants and children, is not an issue of dispute. It was the objective of this study to analyse the extent and the intensity of passive smoke exposure in infants and children with respiratory tract diseases, and compare the information obtained with parents' subjective assessment. At the time of admission to the hospital, the parents of 295 infants and children (aged 1 month to 11 years) were questioned by the physician as to the smoking habits in the families' homes. An HPLC method was employed to determine simultaneously nicotine, cotinine and trans-3'-hydroxycotinine in the children' urine. 2 The sum of the nicotine metabolites turned out to be a sensitive marker in determining passive smoke exposure. Measurements revealed passive smoke exposure in 66% of the children, the frequency in younger children being significantly (P < 0.001) higher than in children over 5 years (84% vs 52%). The average concentration of nicotine metabolites in younger passive smokers was significantly (P<0.00i) higher when compared to the older ones (193 nmol/l vs 86 nmolIl). Forty-nine per cent of the parents assessed that their children had experienced passive smoke exposure, and another 10% emphasised that they only smoked in the absence of their child. In children with cystic fibrosis and bronchial asthma, the number of passive smokers as assessed by their parents were lower by 65% and 29% respectively when compared to the findings obtained from measurements. In children without respiratory diseases, the difference was as little as 18%. 3 Parents when questioned in conjunction with an illness of their children, tended to understate, or even with-hold the truth about, passive smoke exposure. There-fore, reliable information on passive smoke exposure of patients can only be obtained through objective measurements.
Passive smoking among adolescents in Estonia
Authors: Piirna Kersti
Published: April 2003

1 The objective ofthis study was to assess prevalence and patterns of passive smoking in Estonia and to describe how environmental tobacco smoke is likely to initiate the desire in adolescents to start active smoking. 2 A population sample of 2170 students within the age groups of 13-14,15-16 and 17-18 of school grades 8, 10 and 12, respectively, at Tallinn High Schools participated in this study. The data w,ere collected using questionnaires which mainly consisted of structured multiple-choice and a few open questions. 3 Every fourth adolescent in Tallinn was either an occasional or a habitual smoker. 4 Nearly half (48%) of the respondents had no daily exposure to cigarette smoke. Almost one third (31%) was exposed daily for less than 1 h, 15% for 1-5 h and 6% for over 5 h a day. 5 The number of adolescent smokers was higher than non-smokers among those daily inhaling tobacco sidestream smoke. 6 In conclusion, environment gives considerable impact to the development of smoking habits among adolescents. Passive smoking as an inducing factor is associated with higher prevalence of smoking among the adolescents studied.
The association between preand postnatal tobacco smoke exposure and allergic sensitization during early childhood
Authors: Kulig Michael , Luck Werner , Wahn Ulrich ,   Multicentre Allergy Study Group, Germany
Published: April 2003

Aim of our study was to investigate the effect of preand postnatal passive tobacco smoke exposure on the incidence of allergic sensitization.

Patients and methods Specific sensitization to food, outdoor and indoor allergens was determined in 342 children at the age of 1, 2 and 3 years. Parents were asked about their smoking habit at the birth of their children, at 18 months and 3 years of age.

Results Multivariate regression analysis indicated, that during the first 3 years of life, preand postnatally exposed children had a significantly higher risk for sensitization to food allergens compared to children never exposed to tobacco smoke exposure on specific sensitization could bedemonstrated.

Conclusion During early childhood both preand postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization to food allergens.
Cotinine in meconium indicates risk for early respiratory tract infections
Authors: Nuesslein T G , Beckers D , Rieger C H L
Published: April 2003

1 In order to identifypotential risks for lower respiratory tract symptoms during early infancy, the concentration of cotinine was measured in meconium of 91 newborns as a parameter of prenatal exposure to tobacco, and a questionnaire was performed with parents at birth. Infants were followed up for the first year of life by monthly telephone interviews. 2 Lower respiratory tract infections during the first 6 months of life were associated with a high concentration of cotinine in meconium (cotinine higher than median vs lower than median; odds ratio 4.9, 95% confidence interval 1.2 to 20.3), while none of the other variables tested including selfreport of parental, prenatal or postnatal tobacco consumption, parents history of atopy, maternal age, presence of siblings, socio-economic status, duration of gestation, birth weight, gender, and duration of breast feeding were identified as independent risks. The occurrence of a lower respiratory tract infection during the first 6 months of life was predicted correctly in 77% of the infants by a cotinine excretion in meconium exceeding the group median. 3 In conclusion, quantification of cotinine in meconium is preferred to historical parameters as an estimate of the risk for early respiratory tract infections.
Assessment of the exposure of children to environmental tobacco smoke (ETS) by different methods
Authors: Scherer Gerhard , Meger-Kossien Irmtrud , Riedel Kirsten , Renner Thomas , Meger Michael
Published: April 2003

1 In order to elucidate the role of exposure to environ-mental tobacco smoke (ETS) in various acute and chronic illnesses in children, it is important to assess the degree of exposure by suitable methods. For this purpose, we determined the exposure to ETS in 39 children (4-15 years) and 43 adults (16+ years) by questionnaires, personal diffusion samplers for nicotine, and cotinine measurements in saliva and urine. In addition, the influence of the smoking status and the location of the home (urban or suburban) on the benzene exposure of the children was investigated. 2 On average, the 24 children living in homes with at least one smoker were exposed to ETS for 3.1 h/d. This is significantly longer (P<0.001) than the daily exposure time of the 15 children from nonsmoking homes (0.3 h/d). The nicotine concentrations on the personal samplers worn over 7 days were 0.615 and 0.046 tghn3 for children from smoking and nonsmoking homes, respectively (P <0.001). Average salivary cotinine levels were 1.95 ng/ml in children from smoking homes and 0.11 ng/ml in children from nonsmoking homes (P<0.01). The corresponding urinary cotinine levels were 29.4 and 4.5 ng/mg creatinine (P<0.001). There was no difference in the extent of ETS exposure between children and adults from smoking households. Adults from nonsmoking homes tended to have higher ETS exposure than children from nonsmoking homes. 3 Exposure to benzene, which was determined by means of personal samplers, measurements of benzene in exhaled air and of the urinary benzene metabolite trans, trans-muconic acid, was not significantly related to the smoking status of the home but primarily dependent on the location of the home.