bluuebunny/crossref_metadata_2025 huggingface dataset:
Disinfection of Water Containing Natural Organic Matter by Using Ozone-Initiated Radical Reactions
Authors: Cho Min , Chung Hyenmi , Yoon Jeyong
Published: April 2003

Ozone is widely used to disinfect drinking water and wastewater due to its strong biocidal oxidizing properties. Recently, it was reported that hydroxyl radicals (
·
OH), resulting from ozone decomposition, play a significant role in microbial inactivation when
Bacillus subtilis
endospores were used as the test microorganisms in pH controlled distilled water. However, it is not yet known how natural organic matter (NOM), which is ubiquitous in sources of drinking water, affects this process of disinfection by ozone-initiated radical reactions. Two types of water matrix were considered for this study. One is water containing humic acid, which is commercially available. The other is water from the Han River. This study reported that hydroxyl radicals, initiated by the ozone chain reaction, were significantly effective at
B. subtilis
endospore inactivation in water containing NOM, as well as in pH-controlled distilled water. The type of NOM and the pH have a considerable effect on the percentage of disinfection by hydroxyl radicals, which ranged from 20 to 50%. In addition, the theoretical
C̅T
value of hydroxyl radicals for 2-log
B. subtilis
removal was estimated to be about 2.4 × 10
4
times smaller than that of ozone, assuming that there is no synergistic activity between ozone and hydroxyl radicals.
Cloning of a Gene Encoding an Alt a 1 Isoallergen Differentially Expressed by the Necrotrophic Fungus
Alternaria brassicicola
during
Arabidopsis
Infection
Authors: Cramer Robert A. , Lawrence Christopher B.
Published: April 2003

Alternaria
species are considered some of the most important fungi responsible for allergenic morbidity in humans. The
Alternaria
protein that elicits the most intense allergic reaction in humans is Alt a 1, yet no biological function has been identified for this protein. In this study, suppression subtractive hybridization and virtual Northern blots were used to identify and characterize an Alt a 1 homolog in the phytopathogenic fungus
Alternaria brassicicola
. RNA was extracted from
A. brassicicola
spores germinated in water and on leaf surfaces of the
Arabidopsis
ecotype Landsberg for 24 h and used to create cDNA by PCR. Double-stranded cDNA was then used in suppression subtractive hybridization to identify differentially expressed genes. mRNA transcript levels were assessed by virtual Northern blotting. A sequence with significant homology (90% amino acid, 92% cDNA) to the Alt a 1 subunit from
Alternaria alternata
was identified. Virtual Northern blots demonstrated that this homolog, designated Alt b 1 precursor, was highly up-regulated during the infection process of
A. brassicicola
on
Arabidopsis
. The full-length cDNA sequence of Alt b 1 was 815 bp, with an open reading frame of 477 bp. In this preliminary study, we identified a homolog of the major
Alternaria
allergen precursor, Alt a 1, in
A. brassicicola
, designated Alt b 1. This isoallergen is differentially expressed during fungal pathogenesis on
Arabidopsis
, suggesting a possible biological role in pathogenesis.
Production of Diarrheal Enterotoxins and Other Potential Virulence Factors by Veterinary Isolates of
Bacillus
Species Associated with Nongastrointestinal Infections
Authors: Rowan Neil J. , Caldow George , Gemmell Curtis G. , Hunter Iain S.
Published: April 2003

With the exceptions of
Bacillus cereus
and
Bacillus anthracis
,
Bacillus
species are generally perceived to be inconsequential. However, the relevance of other
Bacillus
species as food poisoning organisms and etiological agents in nongastrointestinal infections is being increasingly recognized. Eleven
Bacillus
species isolated from veterinary samples associated with severe nongastrointestinal infections were assessed for the presence and expression of diarrheagenic enterotoxins and other potential virulence factors. PCR studies revealed the presence of DNA sequences encoding hemolysin BL (HBL) enterotoxin complex and
B. cereus
enterotoxin T (BceT) in five
B. cereus
strains and in
Bacillus
coagulans
NB11. Enterotoxin HBL was also harbored by
Bacillus
polymyxa
NB6. After 18 h of growth in brain heart infusion broth, all seven
Bacillus
isolates carrying genes encoding enterotoxin HBL produced this toxin. Cell-free supernatant fluids from all 11
Bacillus
isolates demonstrated cytotoxicity toward human HEp-2 cells; only one
Bacillus
licheniformis
strain adhered to this test cell line, and none of the
Bacillus
isolates were invasive. This study constitutes the first demonstration that
Bacillus
spp. associated with serious nongastrointestinal infections in animals may harbor and express diarrheagenic enterotoxins traditionally linked to toxigenic
B. cereus
.
Direct Profiling of Environmental Microbial Populations by Thermal Dissociation Analysis of Native rRNAs Hybridized to Oligonucleotide Microarrays
Authors: El Fantroussi Said , Urakawa Hidetoshi , Bernhard Anne E. , Kelly John J. , Noble Peter A. , Smidt H. , Yershov G. M. , Stahl David A.
Published: April 2003

Oligonucleotide microarrays were used to profile directly extracted rRNA from environmental microbial populations without PCR amplification. In our initial inspection of two distinct estuarine study sites, the hybridization patterns were reproducible and varied between estuarine sediments of differing salinities. The determination of a thermal dissociation curve (i.e., melting profile) for each probe-target duplex provided information on hybridization specificity, which is essential for confirming adequate discrimination between target and nontarget sequences.
Inhibitory effects of the medicinal herb, Thonningia san gunea, on liver drug metabolizing enzymes of rats
Authors: Gyamfi M A , Hokama N , Oppong-Boachie K , Aniya Y
Published: April 2003

In this study we examined the effect of the aqueous extract of Thonningia sanguinea (T.S.) on 7-ethoxyresorufin 0- deethylase (EROD, CYPlAl), 7-pentoxyresorufin-dealkylase (PROD, CYP2B1/2), 7-methoxyresorufin 0- demethylase (MROD, CYP1A2), aniline hydroxylase (aniline, CYP2E1), p-nitrophenol hydroxylase (PNPH, CYP2E1) and erythromycin N-demethylase (ERDM, CYP3A1) in rat liver in vitro and in vivo. Although T.S. extract increased ERDM activity in induced rat liver microsomes, it showed a dose-dependent inhibitory effectin vitro on other P450 monooxygenase activities particularly EROD and PROD, which are mediated primarily by CYPlAl and CYP2B1/2, respectively. PROD, EROD and MROD activities were also decreased by 18%, 19% and 40%, respectively, in hepatic microsomes prepared from rats treated with T.S. extract for 3 days. Kinetic analysis of CYP activity of 3-methylchloranthrene-induced microsomes demonstrated that T.S. inhibited EROD and MROD activities by a noncompetitive and competitive mechanism, respectively. The analysis of alterations produced by T.S. on PROD kinetic parameters in phenobarbital-induced microsomes suggested that the inhibition is noncompetitive. Pretreatment of rats with T.S. prolonged pentobarbital and phenobarbital sleeping time; however, plasma phenobarbital concentration determined on awakening showed no significant difference between control and T.S.-treated rats. T.S. was also found to be a potent inhibitor of the liver cytosolic glutathione S-transferase. These data suggest that selective modulation of CYP isoenzymes by T.S. might con-tribute to protection of the liver from xenobiotic-induced intoxication or to alteration of the action of drug (s) conco-mitantly administered besides its antioxidative properties.
Dose-dependent toxicity of diphenhydramine overdose
Authors: Radovanovic D , Meier P J , Guirguis M , Lorent J-P , Kupferschmidt H
Published: April 2003

Background: Diphenhydramine (DPHM) overdose is a frequent cause of acute poisoning. Although its clinical features are well known, information about the dose dependent toxicity of DPHM is still scarce. The objective of this study was to investigate the dose-dependent toxicity of DPHM in patients with acute DPHM poisoning.

Methods: We have analyzed retrospectively all well-documented cases with DPHM monointoxications reported by physicians to the Swiss Toxicological Information Centre (STIC) between January 1984 and April 1996. In addition, a prospective study focusing on ingested DPHM doses and severity of symptoms was performed between May 1996 and December 1998.

Results: The retrospective and prospective studies included 232 and 50 patients with DPHM monointoxications, respectively. In both studies, mild symptoms (somnolence, anticholinergic signs, tachycardia, nausea/vomiting) occurred in 55-64%, moderate symptoms (isolated and spontaneously resolving agitation, confusion, hallucinations and ECG disturbances) in 22-27% and severe symptoms (delirium/psychosis, seizures, coma) in 14-18% of patients. Moderate symptoms occurred above ingested doses of 0.3 g DPHM. For severe symptoms the critical dose limit was 1.0 g DPHM. Although the frequency of delirium/psychosis remained constant or even decreased, coma and seizures were significantly (p<0.05) more frequent in the >1.5-g compared with the 1.0-to 1.5-g-dose group.

Conclusions: These data demonstrate a clear dose-dependent acute toxicity of DPHM. They indicate that only patients with DPHM ingestions above 1.0 g are at risk for the development of severe symptoms and, therefore, should be hospitalized. Thus, the results contribute to the data basis required for a cost effective management of patients with DPHM overdose.
Isoniazid – and rifampicin–induced oxidative hepatic injury – protection by N–acetylcysteine
Authors: Attri S , Rana S V , Vaiphei K , Sodhi C P , Katyal R , Goel R C , Nain C K , Singh K
Published: April 2003

The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid-(INH) and rifampicin-(RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg-1 day-1 each and the hepatoprotective dose of NAC was 100 mg kgday-. All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg-1 day-1) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.
Non-fatal ethylene dibromide ingestion
Authors: Singh S , Gupta A , Sharma S , Sud A , Wanchu A , Bambery P
Published: April 2003

Ethylene dibromide (1,2-dibromoethane) is widely used to fumigate grain and fruit in India. However, acute poisoning due to it has rarely been reported in the literature and most of these patients had an fatal outcome. We describe the suicide attempt of a young male who ingested an ampoule (3 ml) of it, developed acute hepatic and renal failure, metabolic acidosis and coagulopathy but survived following supportive measures.
Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system
Authors: O'Brien P J , Slaughter M R , Swain A , Birmingham J M , Greenhill R W , Elcock F , Bugelski P J
Published: April 2003

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion.

We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes.

Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobar-bituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury.

Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r = 0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r = 0.77) and G6PD (130%/110%/190%, r = 0.78).

Both MDA (r = 0.68) and G6PD (r = 0.71) correlated with hepatic ALT, which decreased 27%o/43%/48%, respectively.

Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.
Cholinergic and noncholinergic brain biomarkers of insecticide exposure and effects
Authors: Gupta R C , Goad J T , Milatovic D , Dettbarn W-D
Published: April 2003

The objective of this investigation was to determine the distribution of cholinergic and noncholinergic biomarkers in discrete brain regions (cortex, stem, striatum, hippocampus, and cerebellum) of rats treated with dimethyl sulfoxide (DMSO, controls), and insecticides such as carbofuran (CARB, 1.5 mg/kg, sc), or methyl parathion (MPTH, 5 mg/kg, ip). Both insecticides produced characteristic signs of anticholinesterase nature within 5-7 min after injection. In controls, analyses of the brain regions revealed a wide variability in the values of cholinergic (acetylcholinesterase, AChE) and noncholinergic (creatine kinase, CK; and lactic dehydrogenase, LDH, and their isoenzymes) biomarkers. The highest activities of AChE and LDH were found in the striatum (166±123 μmol/g/h and 57,720±478 IU/l, respectively) and lowest in the cerebellum (118±6 μmol/g/h) and 39,480±918 IU/l, respectively). However, the activity of CK was found highest in the cerebellum (742,560±798 IU/l) and lowest in the hippocampus (353,400±11,696 IU/l). Each brain region showed a characteristic profile of CK and LDH isoenzymes. Among the CK isoenzymes, activity of CK-BB was highest (77.5-89.3%), followed by CK-MM (6.7-15.6%), and least CK-MB (0-6.9%). The cerebellum had no CK-MB activity. In all brain regions, CK-MM isoenzyme had only the CK-MM3 subform. Among the LDH isoenzymes, activity of LDH-4 was highest in all brain regions (23-40%), except the cerebellum in which LDH-1 was highest (29%). Compared to the brain, control serum contained very little CK and LDH activity, but serum had three distinct CK and five distinct LDH iso-enzymes. Unlike brain regions, serum had three CK-MM subforms. Each insecticide induced characteristic alterations in brain biomarkers. AChE activity was maximally inactivated in cortex (90.6%) with CARB, and in cerebellum (95.3%) with MPTH. With either insecticide, the least inhibition of AChE occurred in the striatum. Unlike AChE, carboxylesterase (CarbE) did not show brain regional variability in controls, and its activity was uniformly inhibited in all brain regions by CARB and comparatively greater by MPTH. CARB- or MPTH-induced characteristic alterations in CK, LDH, and their isoenzymes in the brain, which were also reflected in serum, as a result of their leakage from the brain by increased permeability due to depletion of ATP (38-57% and 33-47%, respectively) and phosphocreatine (PCr, 23-42% and 56-65%, respectively).
Glycyrrhizic acid: the assessment of a no effect level
Authors: van Gelderen C E M , Bijlsma J A , van Dokkum W , Savelkoull T J F
Published: April 2003

Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years.

The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid.

The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily.
Metabolic capacity and interindividual variation in toxicokinetics of styrene in volunteers
Authors: Wenkerl M AM , Kežić S , Monster A C , de Wolff F A
Published: April 2003

The aim of the present study was to assess the interindividual variation in styrene toxicokinetics and to correlate this variation with the individual metabolic capacity for cytochromeP450 (CYP), CYP2E1, CYP1A2 and CYP2D6. Twenty male volunteers were exposed on separate occasions to 104±3 and 360 ± 20 mg/m3 of styrene for 1 h while performing 50 W physical exercise on a bicycle ergometer. Styrene concentrations in blood and mandelic (MA) and phenylglyoxylic acid (PGA) in urine were measured. The metabolic capacity was assessed by phenotyping with chlorzoxazone (CYP2El), caffeine (CYP1A2), dextromethorphan (CYP2D6) and antipyrine (CYP450). In addition, for the main styrene-metabolising enzyme, CYP2E1, genotyping for the genetic polymorphisms of the gene was performed. The average pulmonary retention of styrene was 62 ± 7% at both exposure concentrations, and the 24-h excretion of MA and PGA accounted for 58% of the dose at both concentrations. The interindividual variation in styrene kinetics ranged from 19% for the terminal half-life (t1/2,β) of styrene to 41% for the cumulative excretion of MA and PGA. However, no correlation between the apparent blood clearance of styrene (CLapp), t1/2,β of styrene or excretion of MA and PGA on one hand, and the individual metabolic capacity on the other hand was found. Although other explanations cannot be excluded, this lack of correlation might be due to the high apparent blood clearance (1.4 1/ min) of styrene, indicating that styrene metabolism is liver–blood-flow-dependent.
Repeated administration of a mild acute toxic dose of di-n-butyltin dichloride at intervals of 3 weeks induces severe lesions in pancreas and liver of rats
Authors: Merkord J , Weber H , Kröning G , Hennighausen G
Published: April 2003

Di n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Dependingondose [6and8mg/kgintravenous (i.v.) DBTC] andtime (1–24weeks),thelesionsinpancreasdevelopedto apancreaticfibrosisandthelesionsinlivertolivercirrhosis. A single i.v. administration of 4 mg/kg DBTC induces a mild interstitial pancreatitis after 2–4 days followed by a restitutio ad integrum after 21–28 days. In the present study,thelesionsofbiliopancreaticduct,pancreas,andliver of rats after repeated administration of 4 mg/kg DBTC i.v. at intervals of 3 weeks have been investigated. The histopathologicalchangesofpancreasandliverwereexaminedbylight microscopy1,4,and7daysand2,3,4,6,9,and12weeksafter administration of DBTC. Furthermore, pathobiochemical parameters of pancreatitis (amylase and lipase activity in serum), liver lesions (alkaline phosphatase activity and bilirubin in serum), and of fibrosis (hyaluronic acid in serum) were studied. Repeated administration of rats with DBTC (4mg/kgi.v.) atintervals of3weeks induced anacute interstitial pancreatitis and after 9–12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia, inflammation in periportal tract, and necrosis). In serum, elevated levels of alkaline phosphatase, bilirubin, and hyaluronic acid were found. This study demonstrates that the organotin compound induces toxic effects on pancreas and liver of rats by repeated administration of lower doses at long intervals. The risk of exposure to organotin at long intervals should be considered.
Role of iron–dextran on 7,12-dimethylbenz(a) anthracene-initiated and croton oil-promoted cutaneous tumorigenesis in normal and pregnant mice
Authors: Rezazadeh H , Nayebi A R , Athar M
Published: April 2003

Skin chemical carcinogenesis has been divided into the process of initiation, promotion and progression. Earlier, we showed the role of iron overload in the promotion stage of skin carcinogenesis. In this communication, we report that iron overload does not augment croton oil-mediated tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated pregnant mice skin tumorigenesis. Virgin female Swiss mice were given 1 mg iron/mouse/day parenterally for 2 weeks to induce iron overload. After the last injection, a group of mice was left with male mice for 10 days. These animals showed an increase in cutaneous iron concentration as compared to normal mice. Papillomas were induced in mice skin by a single topical application of DMBA as initiator. A week after the initiation, promoting agent, croton oil was applied twice per week for 20 weeks. The appearance of the first tumor (papilloma), number of tumors/mouse and percentage incidence were recorded. When compared to the iron unloaded control and iron overload pregnant groups, the iron overload virgin animals showed an increased incidence of tumors. In iron overload virgin animals, tumors appeared earlier and also the numbers of tumors/mouse were significantly higher. However, in iron overload pregnant animals, diminished tumor incidence was observed and the numbers of tumors matched the result of normal pregnant animals. Our results show that iron overload in pregnant mice does not participate in the augmentation of DMBA and croton oil-induced skin tumorigenesis.
Positive responses to imipramine in the popliteal lymph node assay are due to primary irritation
Authors: Choquet-Kastylevsky G , Tedone R , Descotes J
Published: April 2003

The popliteal lymph node (PLN) assay has long been proposed as a tool to detect immunotoxicants with the potential to induce systemic autoimmunity. A major problem hampering the further validation of this assay is the need to rule out irritants that cause false-positive PLN responses. The anti-depressant, imipramine, has not been reported to induce systemic autoimmune reactions in treated patients, but has been repeatedly found positive in the PLN assay, suggesting that this is a false-positive response. To test this hypothesis, the effects of imipramine were compared to those of 50% ethanol in C57Bl/6 mice. Footpad edema was evidenced in the few days after injection of both ethanol and imipramine. T-cell depletion using monoclonal antibodies against either CD4+ or CD8+T-lymphocytes prior to the PLN assay did not influence the responses to either ethanol or imipramine. Cytokine (TNF, IL-1, IL-1, IL-2R, IL-6, IL-12 and IFN-) fingerprinting of the PLNs after injection of ethanol and imipramine evidenced the same pattern of responses. These results indicate a closely similar pattern of responses following the footpad injection of either imipramine or ethanol. The conclusion can be drawn that imipramine induces positive responses in the PLN assay via primary (nonspecific) irritation.
Parasuicidal poisoning treated in a Greek medical ward: epidemiology and clinical experience
Authors: Hatzitolios A I , Sion M L , Eleftheriadis N P , Toulis E , Efstratiadis G , Vartzopoulos D , Ziakas A G
Published: April 2003

Objective: To study the epidemiology of acute poisoning patients presenting to an acute medical service ward in a Greek hospital between January 1998 and December 2000. Design: Prospective case series. Results: A total of 273 patients with self-poisoning were included in the study. This represented 3.8% of the overall admissions to the unit. The mean age of patients was 33, the most frequent age group being that aged 20–30 years (36.2% of total) with a male-to-female ratio of 1:1.97. Sixty per cent of patients was admitted within 4 h. Those from urban areas comprised 76.2% and 23.8% from rural areas. The most frequently ingested agents were psychopharmaceuticals (37.4%) and analgesics/anti-rheumatics (32.6%). Pesticides (7.7% of total) were most frequently used by patients coming from rural areas (32.3% of patients from rural areas). Alcohol was included in the overdose in 8.4%. Of the patients, 16.2% had a previous history of overdose. In this case series, psychiatric assessment suggested that 52% of the patients had a formal psychotic diagnosis, 21% had personality disorder and 27% had taken an overdose in response to stress. The most frequently documented precipitating factors were family problems and disputes (37%). Unusually, the seasonal distribution in these patients suggested a peak in summer (37.5% of presentations) with lower numbers in spring (30.2%), autumn (17.7%) and winter (14.6%). Of the patients, 23.7% presented in July. A total of 73.5% of patients was conscious, 16.4% was somnolent, 4.5% was in precoma and 5.6% was in coma (GCS <8). Patients who received antidotal therapy comprised 17.9%. Evidence of hepatic dysfunction was observed in 8.9% of patients and renal dysfunction in 3.6%. Extracorporeal techniques for drug removal (hemodialysis and hemoperfusion) were used in 2.2% of patients. Intensive care therapy was required in 11.4% of patients. The mean overall hospitalization time was 3.3 days. The mortality rate was 2.9%. Conclusions: This study shows that the epidemiology of self-harm by overdose in Greece is significantly different in terms of the seasonal presentation from other parts of Europe. The agents ingested and other features are similar to northern Europe. Psychiatric diagnoses are more common in our group than in those reported from northern Europe.
Altered serum cytokine and immunoglobulin levels in the workers exposed to antimony
Authors: Kim H-A , Heo Y , Oh S-Y , Lee K-J , Lawrence D A
Published: April 2003

1 Antimony (Sb), an industrial and environmental toxicant, is known to cause dermatitis and pulmonary inflammations, but the immunomodulatory effects of environmental or occupational exposure to Sb have not been reported. To initiate investigation of Sbinduced alterations of the immune system, the concentrations of the IgG subclasses, IgE, interleukin-2, interferon-g, and interleukin-4 in sera obtained from workers exposed to Sb through antimony trioxide manufacture were determined and compared with those of control subjects. 2 The serum levels of IgG1, an immunoglobulin involved in host defense against many microbial infections, were significantly lower in the sera of Sb-exposed individuals than the controls. The serum concentrations of IgE, an immunoglobulin mediating allergic hypersensitivity, also were lower in the Sb-exposed workers than the controls. In addition, the levels of interleukin-2 and interferon-g, multifunctional cytokines for T-cell mediated immunity, were lowered in the factory workers. 3 A significant positive correlation between IgG4 and urine Sb levels was found among the Sb-exposed workers, indicating a possible role of IgG4 in Sbmediated pulmonary or skin pathogenesis. 4 The present study provides the first report on immune alterations induced by occupational exposure to Sb and suggests that Sb exposure disturbs immunohomeostasis in humans observed as a function of aberrant serum cytokine and immunoglobulin levels, which could influence health.
Serum cytotoxin and oxidant stress markers in N-acetylcysteine treated thioacetamide hepatotoxicity of rats
Authors: Akbay A , Ĉinar K , Uzunalimoglu Ö , Eranil S , Yurdaydin C , Bozkaya H , Bozdayi M
Published: April 2003

N-acetylcysteine (NAC) is a glutathione precursor used to treat several clinical conditions where intracellular oxidant-antioxidant balance is disturbed, among which, acetaminophen induced hepatotoxicity may be counted. In this study, administering thioacetamide (TAA) as a hepatotoxic agent, a rat model of hepatotoxicity has been established, to investigate some of the immune mediated basic oxidant-antioxidant homeostatic mechanisms involved, and potential serum markers for follow-up of disease and treatment. To do this, four experimental groups receiving saline/saline, saline/NAC, saline/TAA and NAC/TAA as intraperitoneal injections, have been formed. Rat serum tumor necrosis factor-a (TNF-α), Interleukin1-β (IL1-β), malondialdehyde (MDA) as a measure of final oxidant damage and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) have been assayed. Hepatocellular damage has been measured via the biochemical estimates ALT, AST and LDH as well as histopathological grading. It was found that both TNF-α and IL1-β were significantly elevated in saline/TAA receivers (P50.01) when compared to NAC/TAA receivers. Serum MDA was also increased in TAA receivers in addition to SOD (P50.05) and GSH-Px (P50.05). Serum nitrite levels have also been assayed to give an estimate of nitric oxide that is suggested as a counter-balancer of oxidant stress. NAC/saline receivers had the highest levels of nitrites in the serum (P50.05). Our results indicate that part of the hepatocellular injury to rat liver, induced by TAA is mediated by oxidative stress caused by the action of cytokines imparted by the enzymatic SOD and GSH-Px and non-enzymatic gaseous nitric oxide mechanisms causing an alleviation on administration of NAC. In addition, TNF-α,IL1-β,MDA, SOD, GSH-Px and nitrites are potential candidates of serum indicators for monitorization of pathophysiological stage of liver disease.
Passive smoking and respiratory symptoms in primary school children in Hong Kong
Authors: Lam T H , Hedley A J , Chung S F , Macfarlane D J ,   Child Health and Activity Research Group (CHARG)
Published: April 2003

1 We aimed to study whether passive smoking is associated with respiratory ill health in primary school children in Hong Kong. 2 In this cross-sectional study, a standardised structured questionnaire was used to obtain information on respiratory symptoms, smokers in the household and smoking habit of the children. A random sample of 30 primary schools was included. Four classes were randomly selected for each school, one class each from each school year of primary 3-6. A total of 3964 children aged 8-13 years completed the questionnaire during October 1995-May 1996. The response rate was over 94%. 3 In 3480 children who had never smoked, after adjusting for gender, age, place of birth and living district, the odds ratios (95% confidence interval) were: (a) throat problems, 1.35 (1.08-1.68); (b) cough, 1.54 (1.28-1.84); (c) phlegm, 1.43 (1.21-1.70); (d) wheezing, 1.21 (0.89-1.41); (e) nose problems, 1.17 (1.02-1.35). The odds ratios increased with increasing number of smokers at home (P for trend < 0.001; except for wheezing, P=0.3). The odds ratios for having any of the above symptoms for one, two and three smokers at home were respectively 1.15 (0.99-1.34), 1.48 (1.16-1.88) and 2.03 (1.47-2.81); P for trend < 0.001. 4 We conclude that the results provide further evidence that passive smoking is a cause of respiratory ill health in school children in Hong Kong.
Mainstream and sidestream cigarette smoke condensates suppress macrophage responsiveness to interferony
Authors: Edwards Kimberlee , Braun Kristen M , Evans Glenn , Sureka Amod O , Fan Samuel
Published: April 2003

Sidestream smoke evolves from the smoldering end of a cigarette while the smoker is not puffing, and contributes substantially to environmental tobacco smoke (ETS). In contrast, main stream smoke emerges from the butt end of the cigarette and is mainly inhaled by the smoker. This study was performed to compare the effects of short-term exposure to cigarette smoke condensates prepared from sidestream (CSCSS) and mainstream cigarette smoke (CSC-MS) on macrophage basal metabolism and responsiveness to two different stimuli, bacterial lipopolysaccharide (LPS) and interferony (IFNy). Despite their generation at different temperatures and their different chemical composition, CSC-SS and CSC-MS had similar effects on macrophages. Both enhanced macrophage basal metabolism and responsiveness to LPS. Macrophage responsiveness to IFNy, assessed by their expression of four functional capacities, was suppressed by both CSC-SS and CSC-MS. The four assessed IFNy-inducible functional capacities were: enhanced phagocytosis of immuoglobulin-opsonized sheep red blood cells, TPAinduced peroxide production, class II major histocompatibility complex expression, and nitric oxide synthesis with LPS co-stimulation. The effects of CSCSS and CSC-MS were similar qualitatively; they differ quantitatively in some cases, with CSC-MS generally effective at lower concentrations (expressed as cigarette-equivalents) than CSCSS. Considering dilution of sidestream smoke in room air and loss during passage through the respiratory system, we expect to deliver the maximal dose to lung macrophages in situ only in rooms dense with smokers. However, only a fraction ofthe maximal dose can partially suppress induction of some fiuctions, such as nitric oxide production and MHC expression. Macrophages play critical roles in tissue modeling during development. Of particular concern are neonates, whose organs are still undergoing growth and development, and are therefore susceptible to impaired development. If involuntary exposure to ETS hinders induction of macrophage functional capacities by cytokines, then development of the lungs and perhaps other organs would be impaired. In general, since macrophages are potent effectors and regulators of immunity, impairment of their responsiveness to cytokine must disrupt the proper functioning of the immune system.
Liver preneoplastic changes in mice treated with the herbicide fomesafen
Authors: Krijt J , Stránská P , Sanitraák J , Chlumská A , Fakan F
Published: April 2003

1 Effect of the diphenyl ether herbicide fomesafen on liver preneoplastic changes and porphyrin biosynthesis was examined in male C57BL/6J mice (0.23% in the diet for 14 months) and ICR mice (0.3% in the diet for 50 weeks). Fomesafen treatment resulted in preneoplastic changes (liver nodules and foci of altered hepatocytes) in both strains, uroporphyria developed only in ICR mice. 2 Iron pretreatment (600 mg/kg as a single dose) accelerated the development of fomesafen-induced preneoplastic changes in both mouse strains. The number of foci containing altered hepatocytes, as well as the number and size of liver nodules, were increased in iron-pretreated animals. 3 A single injection of iron induced marked uroporphyria in C57BL/6J mice after 14 months (liver porphyrin content 102 nmol/g). This uroporphyria was further potentiated by fomesafen administration (208 nmol/g). 4 In ICR mice, liver histology was apparently normal after a 3 month recovery from fomesafen treatment (0.32% for 9 months). Liver porphyrin content (260 nmol/g) started to decrease immediately after fomesafen withdrawal, but was still significantly elevated after 3 months (5 nmol/g), as compared to controls (1 nmol/g). 5 It is concluded that the toxicological evaluation of fomesafen should focus on liver porphyrin biosynthesis.
The comparative arthropathy of fluoroquinolones in dogs
Authors: Takizawa T , Hashimoto K , Minami T , Yamashita S , Owen K
Published: April 2003

1 Fluoroquinolone antibiotics are generally only prescribed to paediatric patients on compassionate grounds. This is because they are known to cause lesions in the cartilage of the major diarthroidal joints in immature experimental animals. As dogs are considered to be the most sensitive species, a series of studies was performed to compare the potential for grepafloxacin (a new fluoroquinolone) to cause arthropathy to that of ofloxacin and ciprofloxacin in juvenile (month old) beagles. 2 Grepafloxacin was administered once daily to male juvenile dogs at dosages of up to 100 mg/kg/day (intravenously), 60 mg/kg/day (orally) or 30 mg/kg/ day (subcutaneously) for 1 week. Blister formation was observed on the surface of the joints in one of the three animals treated with grepafloxacin intravenously at 100 mg/kg/day. No abnormalities were observed at lower dosages or when grepafloxacin was administered orally or subcutaneously, regardless of dose. In animals treated with ofloxacin or ciprofloxacin at dosages of 10-30 mg/kg/day, blister formation or erosion was observed on the surface of joints regardless of dose or route of administration. 3 Histopathological examination of the joint surfaces of affected animals revealed the loss of cartilaginous matrix and chondrocytes, cavitation within the intermediate zone of cartilage accompanied by cartilage fibrillation or chondrocyte clustering, or loss of the surface layer which covers the cavitation (or loss of outer wall of the cavity). These findings were not present in the absence of grossly observed lesions. 4 Absorption following oral administration of grepa-floxacin was low. Examination of plasma concentrations of drug following intravenous administration showed that joint toxicity was seen with ofloxacin and ciprofloxacin at maximum concentrations as low as 3.80 and 4.24 mg/l, respectively, while plasma levels of grepafloxacin of up to 11.95 mg/l failed to cause such lesions. When the concentration of grepafloxacin was 18.69 mg/l a single joint lesion was seen. Following subcutaneous administration of grepafloxacin, systemic exposure (area under the curve) of approximately 1.5 times that seen in man was not associated with joint lesions. However, lesions were noted for ofloxacin and ciprofloxacin treated animals at exposures equal to or below those seen in man. Therefore grepafloxacin appeared to have a relatively low potential for joint toxicity; this was not due to lack of penetration into the synovial fluid.
Hyperlipidaemia in cisplatin-induced nephrotic rats
Authors: Abdel-Gayoum A A , El-Jenjan K B , Ghwarsha K A
Published: April 2003

1 The serum and hepatic lipid concentrations were investigated in rats made nephrotic with a single intraperitoneal injection of cisplatin (6 mg kg-1 b.wt.). 2 The serum creatinine and urea concentrations were estimated as indices of nephrotoxicity, and the serum total bilirubin level as a liver function test. 3 The fasting serum total cholesterol, triglycerides (TG) and the cholesterol fractions associated with the various lipoproteins, as well as hepatic cholesterol and TG contents were also measured, following 5, 10 and 15 days from the cisplatin treatment. 4 The results revealed that on day 5 both serum creatinine and urea concentrations were significantly (P50.01) increased, indicating the peak of nephrotoxicity, with no injurious effects on the liver as indicated by the unaltered serum bilirubin concentration. 5 The nephrotoxicity was accompanied by significant elevations in serum total cholesterol and TG concentrations by 49 and 42%, respectively, with significant (P50.05) correlations between the serum cholesterol and TG concentrations versus the serum urea (r=0.68 and r=0.60, respectively). 6 Among the estimated lipoproteins, very low density lipoprotein (VLDL) cholesterol was severely increased to more than twofold with no severe changes in LDL or HDL-cholesterol fractions. On day 5 the liver also showed significant accumulation of TG with no change in the cholesterol content. 7 Animals killed 10 or 15 days post-cisplatin treatment had all the perturbed parameters returned to the normal levels. 8 The present results indicated that rats exposed to a single cisplatin injection exhibit acute reversible nephrosis on day 5 which was accompanied by dyslipidaemia and accumulated liver TG.
Stimulation of survival capacity in heat shocked cells by subsequent exposure to minute amounts of chemical stressors; role of similarity in hsp-inducing effects
Authors: Wiegant F A C , Souren J E M , van Wijk R
Published: April 2003

1 A brief and moderate heat shock to Reuber H35 hepatoma cells causes a rapid increase in the synthesis of heat shock proteins (hsp) and initiates the development of thermotolerance, which results in an increased ability to survive exposure to otherwise lethal temperatures. 2 We now demonstrate that low doses of various chemical stressors (arsenite, cadmium, mercury, lead, copper, menadione and diethyldithiocarbamate (ddtc)), at concentrations that do not exert any effect in control cultures, are able to enhance the synthesis of hsps and to stimulate the development of thermotolerance when applied to cultures which were pretreated with a mild heat shock. 3 The degree of stimulation appears to be stressorspecific, which is not only observed in the ensuing development of thermotolerance but also in the enhancement of the heat shock-induced synthesis of stress proteins. 4 The different hsps that show an enhanced induction when heat shocked cultures are exposed to the various secondary applied low doses of chemical stressors, were found to resemble the hsp pattern that is characteristic for the secondary stressor and not for the initial heat shock. In other words, the nature of the post-treatment determines the observed pattern of enhanced synthesis of hsps. 5 In order to analyze the origin of the stimulation of survival capacity by low doses of the mentioned stressors, we studied whether the degree of stimulation is determined by the degree of similarity between the overall stress response to heat shock and to the second stress condition when applied singly. 6 The degree in which low doses of chemical stressors stimulate tolerance development and enhance the synthesis of hsps in cells that were previously heat shocked, appears to be related to the degree of similarity in the hsp pattern induced by both stressors. 7 Our results support the notion that low doses of toxic compounds may, under certain conditions, have beneficial effects related to a stimulation of endogenous cytoprotective mechanisms.
Adhesion molecules of blood polymorphonuclear leukocytes and alveolar macrophages in rats: modulation by exposure to ozone
Authors: Hoffer E , Baum Y , Tabak A , Frevert C
Published: April 2003

1 Exposure to elevated levels of ozone results in an infiltration of polymorphonuclear leukocytes (PMNs) into the lungs. The purpose of this study was to investigate whether the ozone-induced inflammatory process is preceded by a change in the expression of adhesion molecules (integrins and selectins) in peripheral blood PMNs and alveolar macrophages in rats. 2 Female Sprague Dawley rats were exposed to air or ozone (1 p.p.m., 2 h). Bronchoalveolar lavage (BAL) was carried out and blood was collected via intracardiac puncture at 0 or 18 h after the exposure. There were no PMN in the BAL fluid at time 0 after the 2 h exposure to ozone. The expression of cell adhesion molecules from the integrin family (represented by CD18) on alveolar macrophages (AM) was lowered. The expression of cell adhesion molecules from the selectin family (represented by CD62L) on blood PMN was not affected by exposure to ozone, while the expression of integrins (CD11b) on blood PMN was lowered. 3 This effect was confirmed by experiments in which plasma of ozone-exposed animals was incubated with PMN from peripheral blood obtained from nonexposed animals. In these experiments, the expression of CD11b on PMNs of non-exposed animals was lower after incubation with plasma from ozone-exposed animals. 4 Our experiments suggest the presence of factor(s) in blood, which cause a decrease in the expression of CD11b on PMNs.
Effects of occupational chronic co-exposure to n-hexane, toluen, and methyl ethyl ketone on NK cell activity and some immunoregulatory cytokine levels in shoe workers
Authors: Yücesoy B , Yücel A , Erdem O , Burgaz S , İmir T , Karakaya A E , Karakaya A
Published: April 2003

1 To evaluate the effects of occupational long-term coexposure to n-hexane, toluen, and methyl ethyl ketone (MEK) on NK cell activity and serum IL-2, g-IFN levels, we studied a group of workers employed in a shoe factory where the jobs include use of glues and adhesives containing mainly n-hexane, and at low concentrations, toluen and MEK. 2 No differences were found in these parameters even in those workers with 3.3-fold higher mean levels of urine, 2,5-Hxdn and approximately twofold higher mean levels of urine hippuric acid as compared to controls. 3 We conclude that chronic co-exposure to n-hexane, toluen, and MEK at these levels is not associated with an impairment on either NK cell activity or serum IL-2 and g-IFN levels.
Human ocular efects from self-reported exposures to Roundup® herbicides
Authors: Acquavella J F , Weber J A , Cullen M R , Cruz O A , Martens M A , Holden L R , Riordan S , Thompson M , Farmer D
Published: April 2003

We evaluated ocular effects from reported human exposures to Roundup® herbicides based on 1513 calls to an American Association of Poison Control Centers (AAPCC) certified regional poison center during the years 1993 through 1997. The preponderance of reported exposures were judged by poison center specialists to result in either no injury (21%) or transient minor symptoms (70%). There was some temporary injury in 2% of cases; one injury took more than 2 weeks to resolve. In no instance did exposure result in permanent change to the structure or function of the eye. Since the representativeness of calls to poison control centers is unknown, several interpretations of these findings are possible. The most conservative interpretation is that there were no serious ocular effects from exposure to Roundups herbicides during a 5 year period among callers to a single regional poison center. A less conservative interpretation would be that severe ocular effects from Roundupg exposures are rare among users of these products.