bluuebunny/crossref_metadata_2025 huggingface dataset:
Efectos del Desempleo y el Sexo sobre la Autoestima Positiva, Negativa y Global
Authors: Velo Jesús F. Salgado , Criado Mar Iglesias
Published: March 2003

En los últimos años, un número importante de investigaciones se dedicaron a estudiar los efectos del desempleo sobre la autoestima. Las investigaciones realizadas hasta el momento han mostrado resultados contradictorios, pues mientras varios investigadores han encontrado menor autoestima en los desempleados, otros no han obtenido este resultado. Estos resultados pueden deberse a una inadecuada consideración de la autoestima como una medida global, cuando está formada por dos componentes, uno positivo y otro negativo. En el presente artículo, la autoestima es evaluada en sus dos componentes. Los resultados indican que el desempleo sólo afecta a la autoestima negativa y que cuando aparecen efectos sobre la autoestima global se deben a un artefacto estadístico.
Empleo del tiempo libre y consumo de drogas en escolares
Authors: Sanz Carlos Alonso , del Barrio Gándara Victoria
Published: March 2003

Este trabajo pretende investigar la relación existente entre el empleo del tiempo libre y el consumo de drogas legales. Mediante un cuestionario aplicado a 277 escolares de 7°. de EGB, se obtuvieron datos acerca de la forma en que emplean su tiempo libre y distintas variables asociadas al consumo de alcohol y tabaco, encontrándose que un patrón «productivo» de empleo del tiempo de ocio se asocia a menores consumos de estas sustancias, mientras que el uso «no productivo» del tiempo libre parece ser un factor de riesgo para el consumo de drogas, obteniéndose algunas conclusiones de utilidad para el diseño de programas de prevención.
Rates of spontaneous reactivation and aging of acetyicholinesterase in human erythrocytes after inhibition by organophosphorus pesticides
Authors: Mason H J , Sams C , Stevenson A J , Rawbone R
Published: April 2003

The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (RjR2) and diethoxy substituted (RjR2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology.

A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.
Effect of thiamine on the cadmium–chelating capacity of thiol compounds
Authors: Tandon S K , Prasad S
Published: April 2003

The influence of thiamine on the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA), diethyldimercapto succinate (DEDMS), a mercapto-13-(2-furyl) acrylic acid (MFA) and a-mercapto-3-(2-thienyl) acrylic acid (MTA) to mobilize cadmium and reverse cadmium-induced biochemical alterations was investigated in cadmiumexposed rats. The thiamine coadministration enhanced the efficacy of MFA and MTA in reducing hepatic and renal burden of cadmium and that of DMSA and DEDMS in mobilizing hepatic cadmium. It also improved the efficacy of DMSA, DEDMS and MFAinreversingthe cadmium-induced increase in urinary alkaline phosphatase and aspartate and alanine amino transaminases. The combined treatment with thiamine and DMSA or MFA restricted the urinary loss of zinc and that with thiamine and DEDMS reduced the loss of fecal copper, a general effect of chelation. In conclusion, the administration of thiamine during chelation therapy in cadmium poisoning may be beneficial and more effective than thiol chelating agents alone, which needs to be confirmed in humans.
Evaluation of cot mattress inner foam as a potential site for microbial generation of toxic gases
Authors: Jenkins R O , Morris T-A , Craig P J , Goessler W , Ostah N , Wills K M
Published: April 2003

Recent reports of biovolatilisation of phosphorus and antimony by anaerobic bacteria and of leaching of phosphorus and antimony fire-retardant additives from PVC cot mattress covers, indicate that the polyurethane inner-foam of cot mattresses could be a site for generation of toxic gases of group 15 elements. A toxic gas hypothesis for sudden infant death syndrome (SIDS) involving polyurethane foam of cot mattresses was proposed and tested experimentally. Levels of antimony, phosphorus, arsenic and bismuth were determined at four sites for 44 SIDS and 50 control (no death) cot mattress foams. There was no evidence to suggest that the levels of these elements in cot mattress foam have a causal relation to SIDS. Leaching of antimony trioxide from PVC mattress covers could account for detectable levels of this element in 52% of the cot mattress samples analysed. Volatile forms of antimony, phosphorus, arsenic and bismuth was not detected in the headspace of mixed or monoseptic cultures of anaerobic bacteria containing polyurethane foam. Past microbial activity had given rise to involatile methylated species of antimony in some of the cot mattress foams tested (61%, n = 24). Abiotic oxidation of biogenic trimethylatimony together with physical adsorption of methylantmony forms to the polyurethane foam matrix could account for the apparent absence of “escaped” volatile antimony species in culture headspaces of incubation vial. There was no evidence to suggest that levels of trimethylantimony or total methylantimony forms in cot mattress foams have a causal relation to SIDS.
Frequency and Markov chain analysis of amino acid sequences of mouse p53
Authors: Wu G
Published: April 2003

The amino acid sequence of mouse p53 was measured according to two-and three-amino-acid sequences. The measured frequency and probability were compared with predicted frequency and probability. Of 389 two-amino-acidsequencesinmousep53,85 (21.851%) and27 (6.941%) sequences can be explained by the predicted frequency and probability accordingto a purely random mechanism. Of 188 non-appearing two-amino-acid sequences in mouse p53, 86 (45.745%) and 32 (17.021%) can be explained by the predicted frequency and probability according to a purely random mechanism; no more than two-amino-acid sequences inmousep53 canbe explained by a purelyrandom mechanism.
Aldicarb poisoning
Authors: Ragouc-Sengler C , Tracqui A , Chavonnet A , Daijardin J B , Simonetti M , Kintz P , Pileire B
Published: April 2003

Aldicarb (2 ethyl-2 (methylthio) propanal o-[(methlamino)-carbonyl] oxime) is a pesticide manufactured since 1965. This carbamate ester is sold under the tradename, Temiks, and is used as insecticide and nematicide. The Environmental Protection Agency has classified aldicarb in the highest toxicity category and has defined a strict control for its delivery and use. In Brazil and the Caribbean island, aldicarb is illegally used as a household rodenticide with a widespread risk of poisoning. Our study presents the first review of aldicarb poisoning circumstances associated with cliical and analytical findings. Moreover, the oxime treament is discussed. Eighteen patients with cholinergic symptoms admitted to the Emergency Unit and two deceased with a history of aldicarb poisoning were included in the study. As agricultural workers, only two of them could legally use Temikg. Seventy percent of the patients was managed by the Emergency Mobil Unit. Serum cholinesterase activity was always lower than 30% of the normal range and aldicarb was identified by UV spectra and retention time after liquid chromatogrphy separation. The most common muscarinic effect was diarrhea, the main nicotinic sign fasciculation and almost half of the poisoned patients had central nervous system (CNS) depression (Glasgow Coma Score lower than 8). Four patients had serious conduction abnoralities and two of them died. These results suggest that aldicarb intoxication is always severe. Oxime treatment did not produce side effects and should be recommended whenever the pesticide involved is unknown. Effective measures should be implemented to stamp out the illicit use of aldicarb.
Effects of antioxidants and a caspase inhibitor on chioramphenicol-induced toxicity of human bone marrow and HL-60 cells
Authors: Kong C T , Holt D E , Ma S K , Lie A KW , Chan L C
Published: April 2003

Chloramphenicol (CAP), a board spectrum antibiotic widely used in many developing countries, has toxic side effects on bone marrow, the most serious of which is aplastic anemia. Recent studies suggest that effects of CAP on suppressing hematopoietic colony formation may be abrogated by antioxidants. In addition, there is preliminary evidence that CAP induces apoptosis in hemopoietic stem cells, leading to aplastic anemia. We have been unable to demonstrate the protective effects of a variety ofantioxidants on CAP-induced suppression of burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte/ monocyte (CFUGM). Using flow cytometry, we have, however, confirmed that CAP can induce apoptosis in purified human bone marrow CD34 + cells. We also showed that a caspase inhibitor, Z-VAD.fmk, can ameliorate the apoptotic-inducing effects of CAP in the HL-60 cell line.
Amelioration of fluoride-induced hypocalcaemia by vitamins
Authors: Sherlin D M Guna , Verma R J
Published: April 2003

Oral administration of sodium fluoride (40 mg/kg body weight) from day 6 of gestation to day 21 of lactation caused, compared with vehicle control, significantly lowered level of calcium and phosphorus in the serum of both P and F1 generation rats.Administration of vitamin C (50mg/kgbody weight), D (2 ng/0.2 ml olive oil/animal), E (2 mg/0.2 ml olive oil/animal) and a combination (vitamin C + D + E) along with NaF caused significant amelioration in serum calcium in P generation and serum phosphorus in both P and F1, generation rats as compared with only NaF-treated group. Serum calcium concentration was only partially recovered (P and F1 generation) on NaF withdrawal during lactation, as well as, on cotreatment (F1 generation) with vitamins. However, serum phosphorus level was significantly recovered on NaF withdrawal.
Plasma absorption and ultrastructural changes of rat testicular cells induced by lindane
Authors: Suwalsky M , Villena F , Marcus D , Ronco A M
Published: April 2003

This paper describes, for the first time, how topical application in rats of a commercial preparation of lindane widely used in public health, at similar doses and routes of administration as in humans, leads to rapid absorption and accumulation of lindane in the testes. An early peak of absorption was detected in plasma 6 h after topical treatment of male Wistar rats with a commercial preparation of 1% lindane (Plomurol). Higher plasma levels were observed after repetitive doses of 60 mg/kg b.w., the amount recommended for the treatment of scabies and pediculosis in humans in several countries. A residue level of 7.4±0.67,ag/g was found in testicular tissue 6 h after a single daily topical application for 4 consecutive days. The ultrastructural study of testicular interstitial cells exposed to dermal application of lindane (Plomurol®) revealed widespread damage of a great number ofLeydig cells, some ofwhich were completely disintegrated.
Astrocyte phenotype and prevention against oxidative damage in neurotoxicity
Authors: Pentreath V W , Slamon N D
Published: April 2003

Astrocytes possess a potent array of protective systems. These are chiefly targeted against oxidised products and radicals, which are frequently present in increased amounts following exposure of nervous tissue to a range of toxic insults. Following exposure to the toxic chemicals astrocytes commonly respond by alteration in phenotype with upregu-lation of a large number of molecules, including those controlling the protective systems. This article summarizes evidence, largely obtained from in vitro studies, which supports the concept that some of the changes in astrocyte phenotype are associated with increased protection against the cytotoxicity caused by the oxidative damage that results from exposure to range of neurotoxicants.
Assessment of thyroid function in pesticide formulators
Authors: Zaidi S SA , Bhatnagar V K , Gandhi S J , Shah M P , Kulkarni P K , Saiyed H N
Published: April 2003

Thirty male pesticide formulators exposed to the dust and liquid formulation of endosulfan, quinalphos, chlorpyriphos, monocrotophos, lindane, parathion, phorate, and fenvalerate and 20 comparable control subjects from the same area of study were examined for the evaluation of thyroid function tests. The level of TSH was elevated (about 28%) in pesticide formulators as compared to a control group, but the increase was statistically insignificant. Based on the individual TSH measurement, 3 of 30 formulators had isolated elevated levels of TSH and seem to have acquired sub-clinical hypothyroidism; five had TSH values slightly elevated to the upper boarder line (4.03,uIU/ml); and the majority of formulators (N= 22) had TSH values in the normal range varying from 1.29 to 3.9 pIU/ml. Total T3 was suppressed significantly (P <0.01) in formulators, while marginal decrease (about 7%) was noticed in T4 level. This studyindicatedthyroidfunctionimpairmentinfewpesticide formulators.
Chemical hormesis: its historical foundations as a biological hypothesis
Authors: Calabrese E J , Baldwin L A
Published: April 2003

Despite the long history of hormesis-related experimental research no systematic effort to describe its early history has been undertaken. The present paper attempts to reconstruct and assess the early history of such research and to evaluate how advances in related scientific fields affected the course of hormesis-related research. The purpose of this paper is not only to satisfy this gap in current knowledge, but also to provide a foundation for the assessment of how the concept of hormetic dose-response relationships may have affected the nature of the bioassay especially with respect to hazard assessment practices within a modern risk assessment Eramework.
The marginalization of hormesis
Authors: Calabrese E J , Baldwin L A
Published: April 2003

Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades ofthe 20th century. These factors include: (a) the close-association of hormesis with homeopathy lead to the hostility of modern medicine toward homeopathy thereby creating a guilt by association framework, and the carry-over influence of that hostility in the judgements of medically-based pharmacologists/ toxicologists toward hormesis; (b) the emphasis of high dose effects linked with a lack of appreciation of the significance of the implications of low dose stimulatory effects; (c) the lack of an evolutionary-based mechanism(s) to account for hormetic effects; and (d) the lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.
Glucocorticoid–dependent maintenance of CYP2C11–dependent oxidation in male rat liver in vivo
Authors: Murray M
Published: April 2003

1 Hormonal factors participate in the regulation of xenobiotic metabolising enzymes in liver. Hepatic xenobiotic oxidation capacity is decreased in adrena-lectomised rats, which directly implicates adrenal hormones in the control of cytochrome P450 (CYP) expression. In addition, recent studies in cultured hepatocytes have demonstrated that low concentra-tions of glucocorticoid upregulate the male-specific CYP2C11, which is a major enzyme that catalyses xenobiotic and steroid hydroxylations in rat liver. The present study evaluated whether glucocorticoid or mineralocorticoid may be the adrenal factor that contributes to the in vivo expression of CYP2C11 in liver. 2 Adrenalectomy of male rats selectively decreased CYP2C11-dependent 2a-/16a-hydroxylation of testos-terone and other steroid substrates to 60-70% of control, whereas activities mediated by other constitu-tive CYPs were unaffected. The decrease in CYP2C11 activity was due to impaired protein expression in liver after adrenalectomy. Administration of dexametha-sone (DEX; 0.2 mg/kg i.p. daily for 6 days) restored CYP2C11 activity and protein, whereas the mineralo-corticoid deoxycorticosterone (DOC) and adrenocorti-cotropic hormone (ACTH) were ineffective. 3 These findings establish that glucocorticoids have a partial role in the maintenance of CYP2C11 expression and associated microsomal oxidation in liver and provide a physiological correlate for similar observa-tions made in vitro in hepatocyte culture.
Steroidogenic alterations in testes and sera of rats exposed to trichioroethylene (TCE) by inhalation
Authors: Kumar P , Prasad A K , Dutta K K
Published: April 2003

1 Trichloroethylene (TCE) is an organic unsaturated solvent used in dry cleaning, metal degreasing, thinner for paints/varnishes, anaesthetic agents etc. Human beings are considerably exposed to TCE vapours by inhalation route. 2 TCE has been reported to induce spontaneous abor- tions and congenital cardiac malformation in occupa- tionally exposed women. However, scanty on-line information is available regarding toxic effects of TCE on male reproductive efficiency in experimental animals. 3 Our earlier observations with TCE inhalation in male rats (376 p.p.m., 4 h/day, 5 days a week) for 12 and 24 weeks using whole body dynamic inhalation chamber consistently showed significant decrease (P< 0.05) in total epididymal sperm count and sperm motility. The mating experiments of above TCE inhaled rats with virgin unexposed females showed significantly de- creased fertility. 4 These observations prompted us to investigate whether or not primary testicular steroidal precursors (choles- terol and ascorbic acid) and testosterone have any role in TCE induced significantly decreased epididymal sperm count, sperm motility and overall male repro- ductive inefficiency resulting therefrom. 5 The results indicate significant decrease (P< 0.05) in total epididymal sperm count, sperm motility, specific activities of enzymes Glucose 6-p dehydrogenase (G6PDH) and 17,B hydroxy steroid dehydrogenase (1 7fHSD) with concomitant decrease in serum testos- terone concentrations in TCE inhaled rats showing reduced male reproductive efficiency. There was net accumulation in total cholesterol contents in testes of TCE exposed rats. 6 The findings in the present study indicate possible impairment of testosterone biosynthesis in TCE in- haled rats after 12 and 24 weeks. These findings also serve in parts to elucidate the mechanism of repro- ductive inefficiency in TCE exposed rats. The role of testosterone in this phenomenon is being reported for the first time.
The in vitro percutaneous penetration of chiorpyrifos
Authors: Griffin P , Payne M , Mason H , Freedlander E , Curran A D , Cocker J
Published: April 2003

Chlorpyrifos is a widely used organophosphate pesticide. In order to study the pharmacokinetics of the penetration of chlorpyrifos through human skin we measured the percutaneous penetration of chlorpyrifos through human skin using an in vitro flow through apparatus. The chlorpyrifos was applied to the skin as a commercial concentrate or as a reference standard dissolved in ethanol. There was a significant difference (P=0.03) between the rate of penetration from the commercial concentrate (9.0 nmoles cm-2 h-) and that from the reference standard (4.9 nmoles cm-2 h-). Each experi- ment was run for 24 h. The recoveries from experiments where chlorpyrifos was applied to the skin as a commercial concentrate and as a reference standard dissolved in ethanol were, respectively, in total 91 and 87% of the applied dose of which 15 and 10% was recovered from the skin, 56 and 66% was recovered from the surface of the skin and 20 and 11% was recovered from the receptor fluid. There was a significant difference in the recoveries from the skin but there was no significant difference in the recoveries from the surface of the skin. We concluded that the majority of a dermal dose of chlorpyrifos was still present at or in the surface ofthe skin 24 h after application of a dermal dose. Because chlorpyr- ifos was recovered from the skin after 24 h, it is possible that the skin could act as a reservoir and release chlorpyrifos over a longer period. We also conclude that the solvent vehicle for chlorpyrifos can affect the rate of penetration of the pesticide.
An assessment of the in vitro toxicology of Clostri di urn perfringens type D ε-toxin in human and animal cells
Authors: Shortt S J , Titball R W , Lindsay C D
Published: April 2003

The epithelial Madin Darby canine kidney (MDCK) cell line and 17 human cell lines were examined for sensitivity to Clostridium perfringens type D a-toxin. MDCK cells were confirmed as being sensitive to the toxin. In addition, the Caucasian renal leiomyoblastoma (G-402) human cell line was identified as being ε-toxin sensitive. Using the MTS/PMS assay system the concentration of toxin reducing cell culture viability by 50% (LC50) was found to be 2 ug/ml in MDCK cells. The LC50 for G-402 cells was 280,ug/ml. a-Toxin was found to be rapid acting in MDCK cells exposed to a maximum lethal dose of the toxin (40% loss of viability after a 0.5 h exposure), but slower acting in G-402 cells (40% loss of viability after 1.7 h exposure). Photomicrography of toxin exposed cultures indicated necrotic cell death on exposure to a-toxin. Investigations using an antibody probe indicated that ε-toxin could bind to many cell surface proteins in both MDCK, G-402 and a toxin insensitive human cell line (CAKI-2). It has previously been found that the toxin may bind to the cell surface via glycosylated moieties. However, exposing MDCK and G-402 cells to a-toxin in the presence of sialic acid and several different sugars did not reduce the lethal effects of the toxin.
Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents
Authors: Hendrickx A G , Makori N , Peterson P
Published: April 2003

There are close physiologic similarities between humans and macaques that make them well suited for preclinical testing of biopharmaceutics. These include menstrual cycles of similar length and hormonal control, comparable cellular and endocrine processes of implantation, and similar time-tables of prenatal development. Three teratogenic agents have induced abnormal development of the macaque thymus that is a key organ in the development of the fetal immune system. Embryonic exposure to triamcinolone acetonide, a potent corticosteroid, during critical periods of thymus development caused marked hypoplasia, depletion of thymic lymphocytes, and reduction of epithelial elements. Aplasia and hypoplasia of the thymus were a distinct feature of the “retinoid syndrome” in cynomolgus macaques following exposure to 13-cis-retinoic acid (Accutane) in early pregnancy, the time of neural crest migration. Experimentally induced zinc deficiency in rhesus macaques from conception to 1-year of age caused severe alterations in immunocompetence. More recent studies have shown that the levels of IgG and IgA in cervicovaginal lavages of the rhesus macaque exhibit specific temporal patterns during the normal menstrual cycle. Taken together, theses data suggest that several macaque species are appropriate animal models for preclinical safety assessment of immunomodulatory drugs. Current teratology protocols in these models may require slight modifications to adequately assess the safety of these biologics.
Preclinical development of keliximab, a Primatized™ anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies
Authors: Bugelskil P J , Herzykl D J , Rehm S , Harmsen A G , Gore E V , Williams D M , Maleeff B E , Badger A M , Truneh A , O'Brien S R , Macial R A , Wier P J , Morgan D G , Hart T K
Published: April 2003

The preclinical safety assessment of biopharmaceuticals necessitates that studies be conducted in species in which the products are pharmacologically active. Monoclonal anti-bodies are a promising class ofbiopharmaceuticals for many disease indications; however, by design, these agents tend to have limited species cross-reactivity and tend to only be active in primates. Keliximab is a human-cynomolgus monkey chimeric (Primatized&) monoclonal antibody with specificity for human and chimpanzee CD4. In order to conduct a comprehensive preclinical safety assessment of this antibody to support chronic treatment of rheumatoid arthritis in patients, a human CD4 transgenic mouse was used for chronic and reproductive toxicity studies and for genotoxic studies. In addition, immunotoxicity studies were conducted in these mice with Candida albicans, Pneumo- cystis carinii and B16 melanoma cells to assess the effects of keliximab on host resistance to infection and immunosur-veillance to neoplasia. The results of these studies found keliximab to be well tolerated with the only effects observed being related to its pharmacologic activity on CD4 + T lymphocytes. The use of transgenic mice expressing human proteins provides a useful alternative to studies in chimpan-zees with biopharmaceutical agents having limited species cross-reactivity.
Inhibitory effect of Emblica officinals on the in vivo clastogenicity of benzo alpyrene and acyclophosphamide in mice
Authors: Sharma N , Trikha P , Athar M , Raisuddin S
Published: April 2003

Benzo [α] pyrene (B[α]P) and cyclophosphamide (CP) are potent carcinogens/mutagens. Effect of Emblica officinalis extract administration on the in vivo genotoxi-city of B[α]P and CP was studied using bone marrow chromosomal aberration and micronucleus induction tests in mice.

Three doses (50,250 and 500mg/kgbodyweight) oftheplant extractwere administered orallyfor 7 consecutive days prior to the administration of single dose of mutagens (B[α]P 125 mg/kg oral; CP 40 mg/kg i.p.).

It was found that administration of 250 and 500 mg/kg of E. officinalis extract significantly inhibited the genotoxi-city of B [α] P as well as CP in both the assay systems. Administration of 50 mg/kg of the plant extract had no inhibitory effect.

Vitamin C, a major constituent of E. officinalis when administered at dose level of 9 mg/kg b.w. (the approx-imate estimated amount present in the highest dose of plant extract, i.e. 500 mg) for 7 days did inhibit chromosomal aberrations and micronuclei induction, but not in a significant manner.

Effect of administration of the abovementioned effective doses (250 and 500 mg/kg oral for 7 days) of plant extract and vitamin C (9 mg/kg oral for 7 days) on the hepatic activation and detoxification enzymes was also studied. Significant induction in the levels of glutathione content (GSH) and of antioxidant and detoxification enzymes viz., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S transferase (GST) resulted from plant extract treatment to animals. On the other hand, cytochrome P 450 level was significantly decreased in the plant-extract-treated animals. There was no significant change in cytochrome P 450, GSH contents and activities of enzymes on treatment with vitamin C.

The data indicate that the possible mechanism of inhibition by plant extract is mediated by its modulatory effect on hepatic activation and disposition processes.
Toxicity of ingested formalin and its management
Authors: Pandey C K , Agarwal A , Baronia A , Singh N
Published: April 2003

Formaldehyde is a physiological intermediary metabolite taking part in many biological process in the body. It is a constituent of many items of daily use, including foods. It is also used in medicine for treatment of some conditions. A 40% solution offormaldehyde in water is known as formalin. Formalin is irritating, corrosive and toxic and absorbed from all surfaces of the body. Ingestion is rare because of alarming odour and irritant effect but documented in accidental, homicidal or suicidal attempts. Ingestion can lead to immediate deleterious effects on almost all systems of the body including gastrointestinal tract, central nervous system, cardiovascular system and hepato-renal system, causing gastrointestinal hemorrhage, cardiovascular collapse, unconsciousness or convulsions, severe metabolic acidosis and acute respiratory distress syndrome. No specific antidote is available. Treatment of toxicity is supportive care of the various organ systems. Multidisciplinary approach is required for proper management.
Does caloric restriction induce hormesis?
Authors: Turturro A , Hass B S , Hart R W
Published: April 2003

The question of whether caloric restriction (CR) is hormetic is addressed in terms of two common defini-tions of the term. In terms of the older definition, i.e., a growth-stimulatory effect when lower doses of a compound which resulted in growth inhibition at higher doses, CR is better characterized as a co-hormetic (i.e., a paradigm which at relatively “low doses,” in combina-tion with some stimulus, will evince increased growth (proliferation) and at higher “doses” will inhibit this increased proliferation) rather than a hormetic agent. Mechanisms such as cellular selection of cellular subpopulations, increases in receptor efficiency, and preservation of cellular proliferative potential can inter-act with agents and produce increased growth as long as the CR is not too severe. In terms of a broader definition, i.e., nonmonotonic dose-response behavior of a compound for any adverse response, CR appears to be hormetic, both as a result of body weight (BW) loss and other potential mechanisms. The impact of changes in BW, or frank CR, can be considered a component of every test for hormesis, and is thus capable for interaction with any other agent. The changes that BW loss (or CR) induce are so profound that any aspect of an agent's action-metabolism, pharmacokinetics, pharmacodynamics-can modulate the response of an organism to an agent. Similarly, other effects of a chemical that induce BW loss, e.g., physical activity or temperature dysregulation, can also induce dose-response curves that appear hormetic. The interaction of the hormetic agents of BW loss and CR can influence agent tests. Controlling these factors may make it possible to dissect the key components of a hormetic response. In addition, the effects of CR or BW loss appear to extrapolate well across species [Colman R, Kemnitz JW. Aging experi-ments using nonhuman primates. In: Yu BP (Ed), Methods in Aging Research. CRC Press, Boca Raton, FL, 1999, pp. 249-267]. Thus there is some reason to believe that these hormetic factors may be important for humans, and may already be a factor for tests of potentially adverse agents already conducted in humans.
Mechanism for uptake of silica particles by monocytic U937 cells
Authors: Hetland G , Namork E , Schwarze P E , Aase A
Published: April 2003

We examined the mechanism for uptake by monocytic cells of particles found in the atmosphere of some industrial work places. As a model system, irregular crystalline silica particles (SPs), sphere-like cryptocrystalline microsilica particles (MPs) and carbon particles (CPs) were exposed to pro-monocytic U937 cells. Plasma-treated SP and MP, but not CP, activated the alternative complement pathway, but bound little C3b. However, all particles adsorbed serum IgG, IgA and IgM unspecifically. Phenotyping of U937 cells for complement receptors (CRs) and Fcγ receptors (FcγRs) showed that interferon γ (INFγ) increased expression of FcγRI, CR3 (CD11b/CD18) and CR4 (CD11c/CD18) and that phorbol-12-myristate-13-acetate (PMA) increased expression of CR4. Scanning electron microscopy (SEM) demonstrated higher phagocytosis of plasma-treated SP than native SP by both PMA and INFγ-stimulated, but not unstimulated, cells. MP and CP could not be distinguished from cellular structures. Inhibition experiments in SEM revealed uptake of heparin-plasma-treated SP via Fc'yRI on INFγ-stimulated U937 cells, but could not exclude possible participation of CR3. The results indicate that plasma-treated SPs bind Ig and are internalized by differentiated monocytic cells via FcγR1, which is known to trigger cellular production of toxic oxygen species that may induce pulmonary inflammation in vivo.
Improvements in the packaging of drugs and chemicals may reduce the likelihood of severe intentional poisonings in adults
Authors: Chan T YK
Published: April 2003

Because of the inconvenience and longer time required to punch out the tablets, strip packaging may reduce the number of tablets that can be readily swallowed by adults with self-poisonings. In fact, hospital-based studies of paracetamol poisoning in the U.K. and Hong Kong have shown that blister packs were associated with fewer tablets being ingested and large overdoses were mostly from loose preparations. In Australia, following the change in packa-ging for carbamazepine from bottles of tablets to blister packs, a marked decrease in the reported number of tablets ingested by patients was seen. Reducing the maximum number of tablets that can be available in individual preparations or prescriptions may also reduce the likelihood of severe poisonings. In France, but not in the UK, the content of each pack of paracetamol has been legally limited to 8 g. This was thought to be one reason why severe liver damage and deaths after paracetamol poisonings are less common in France than in the UK. Medicated oils containing methyl salicylate pose the threat of rapid-onset, severe salicylate poisoning if swallowed. To reduce the amount of methyl salicylate that can be readily swallowed, the methyl salicylate content and the size of the bottle and its opening should be restricted. In adults with Dettol poisoning, serious complications such as pulmonary aspiration are more likely if a large amount is ingested. Similarly, the risk may be reduced by restricting the size of bottle and its opening.
Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma cell lines
Authors: Goll V , Viollon-Abadie C , Nicod L , Richert L
Published: April 2003

We examined the effects of various peroxisome proliferators (PPs) such as the hypolipidaemic agents clofibric acid (CLO), bezafibrate (BEZA), ciprofibrate (CIPRO) and nafenopin (NAFE) and the plasticizer di-(2-ethylhexyl)phthalate (DEHP) on peroxisomal enzyme activities, apoptosis and DNA synthesis in rat FaO and human HepG2 hepatoma cell lines. Both growing and confluent cultures were treated with PPs (250 mM) for 48 or 72 h. In accordance with our previous observations in PP-treated primary hepatocyte cultures of rat and human origin,1the various PPs increased peroxisomal enzyme activities in rat FaO cells but not in human HepG2 cells. PPs strongly induced apoptosis in FaO cells. They did not affect TGFb-induced apoptosis, with the exception of DEHP and NAFE, respectively blocking and increasing induced apoptosis in confluent cultures. Moreover, PPs produced a minor, but significant, decrease in DNA synthesis in FaO cells. PPs also decreased DNA synthesis in growing HepG2 cells, and CLO, CIPRO and NAFE induced apoptosis in confluent HepG2 cultures. This is in opposition with the effects of PPs on primary hepatocyte cultures, i.e. inhibition of both spontaneous and TGFb-induced apoptosis and increases in DNA synthesis in rat hepatocytes, and unchanged mitosis-apoptosis balance in human hepatocytes.
Cholinesterase activities determination in frozen blood samples: an improvement to the occupational monitoring in developing countries
Authors: Oliveira-Silva J J , Alves S R , Inacio A F , Meyer A , Sarcinelli P de N , Mattos R de C , Ferreira M de FA , Cunha J C , Moreira J C
Published: April 2003

1 Studies were carried out on rural workers in Brazil to determine the decrease in the activity of plasma butyrylcholinesterase (BChE), erythrocyte cholinesterase (AChE) associated with exposure to organophosphorus pesticides (OP). The goal of this work is to help prevent injury to these workers.

2 In developing countries the distance between area of pesticide use and reference laboratories is a drawback for analytical techniques, since cholinesterase activity determinations require fresh blood samples. Field methodologies can be a useful alternative to laboratory tests, however they are not as sensitive as those found in laboratories.

3 The modification of Ellman's Method presented in this paper allows blood samples to be frozen and maintain enzymatic stability: 7 days for AChE and 3 days for BChE. The proposed method is also more sensitive than Ellman's Method Modified by Magnotti (EMMM).

4 The results suggest that the Ellman Method Modified by Oliveira-Silva (EMMOS) is valid for monitoring procedures. This method represents an important contribution to the process of monitoring OP exposures, since the evaluations no longer have to be conducted near the site of OP use.
Amitraz poisoning in children
Authors: Yaramis A , Soker M , Bilici M
Published: April 2003

Amitraz is an acaricide and insecticide indicated for the treatment of generalized demodicosis in dogs and for the control of ticks and mites in cattle and sheep. There is little information available in the human literature about the toxicology of the product. In this study, the clinical and laboratory features of amitraz poisoning in 11 children are presented. The age range ofthe patients was 2-1/2 to 6 years. Accidental ingestion of an improperly stored liquid pesticide was determined in all patients. Unconsciousness (100%), drowsiness (100%), and myosis (84%) were the most common abnormal signs; 45%, 27%, and 18%o of patients had bradycardia, respiratory insufficiency, and hypotension, respectively. All of the patients were treated with atropine, gastric lavage, activated charcoal, and supportive care. Although the patients had a prompt response to therapy, three patients required multiple doses of atropine during a 24-h period. This study revealed that clinical poisoning by oral route emerged within 30-90 min and that central nervous system (CNS) depression, which is the most important sign, resolved within 8-1/2-14 h. All cases were discharged.
Epigenetic mechanisms of chemical carcinogenesis
Authors: Klaunig J E , Kamendulis L M , Xu Yong
Published: April 2003

Chemically induced cancer is a multi-step process involving damage to the genome initially followed by clonal expansion of the DNA damaged cell eventually leading to a neoplasm. Chemical carcinogens have been shown to impact at all of the stages of the tumorigenesis process. It has become apparent that chemical and physical agents that induce cancer may do so through several different cellular and molecular mechanisms. Epigenetic (nongenotoxic) chemical carcinogens are those agents that function to induce tumor formation by mechanisms exclusive of direct modification or damage to DNA. These agents appear to modulate cell growth and cell death and exhibit dose response relationships between exposure and tumor formation. The exact and/or exclusive mechanisms by which these agents function have not been established, however, changes in cell growth regulation and gene expression are important to tumor formation. This review focuses on several potential mechanisms and cellular processes that may be involved in nongenotoxic chemical carcinogenesis.
Near-fatal gamma-butyrolactone intoxication—first report in the UK
Authors: Dupont P , Thornton J
Published: April 2003

Gamma-hydroxybutyrate (GHB) is a compound used in the treatment of alcohol withdrawal, narcolepsy, and for induction of anaesthesia. It is also contained in many products illegally marketed as “dietary supplements” and is increasingly being recognised as a potential drug of abuse. We report the case of a 44-year-old man who suffered coma and life-threatening respiratory depression following an accidental overdose of the GHB prodrug, gamma-butyro-lactone (GBL), contained in a “health drink”. He made a full recovery following appropriate supportive treatment. GHB toxicity should be included in the differential diagnosis of patients with altered mental state, particularly where there is a history of recreational drug abuse.
Differential toxicity expression of gentamicin in five-sixths nephrectomized rats assigned to three progressive stages of renal dysfunction — establishment of a new screening approach
Authors: Barata K , Yoshida M , Hokao R , Imai S , Takahashi S , Harada E , Maekawa A
Published: April 2003

Progressive renal dysfunction in 5/6 nephrectomized (NX) rats can be physiologically divided into three stages, coinciding with morphological stages, after definition of physiological parameters for identification of stage. Now, for the establishment of a toxicity screening approach using 5/6 NX rats, our concept, “Differential toxicity synchronized with renal dysfunction process could be identified using 5/6 NX rats” was examined by dosing gentamicin. Firstly, electrophoretic fractional changes of urinary proteins during gentamicin treatment were clarified with determination of amino acid sequences and the three differential features were proven, revealing the unpredictable depression of urinary albumin with progression of the stages in NX rats. Secondly, marked elevation of urinary lactate dehydrogenase (LDH) and glucose (GLU) was evident, indicating the intensified hypoxic conditions and glycolysis in tubular cells synchronized with increased tubular damage. Thirdly, these transit metabolic changes were proven as intensive cause for the advancement of renal dysfunction by the reduction of FRelectrolytes and water at the end of each dosing period. These results indicate that toxicity studies of newly developed drugs using 5/6 NX rats have potentiality prior to clinical dosing to the patients.
Stimulation of myelopoiesis in Lister a monocytogenes-infected mice by an aggregated polymer isolated from Asp ergillus oryzae
Authors: de Melo A , Justo G Z , de Souza Queiroz M L
Published: April 2003

In this work, we investigated the effects of the proteic aggregated polymer of magnesium ammonium phospholi-noleate-palmitoleate anhydride (MAPA) isolated from Aspergillus oryzae on the growth and differentiation ofbone marrow granulocyte-macrophage progenitor cells (CFU-GM) inListeriamonocytogenes-infectedmice.Asignificant reduction in the CFU-GM numberwas observed in the initial phase of infection with a sublethal dose of Listeria. Treatment of mice with 0.5, 2.0 and 5.0 mg/kg MAPA for 7 days prior to infection significantly stimulated myelopoiesis in a dose-dependent manner. Moreover, treatment with 0.5 and 5.0 mg/kg MAPA resulted in 30%/6 and 40% cures of mice lethally infected with Listeria, respectively. MAPA added directly to the culture dishes hardly affected colony formation by bone marrow cells, suggesting an indirect effect ofthis compound on myelopoiesis in vivo. In summary, the data show that MAPA can modulate the CFU-GM generation and antibacterial resistance in listeriosis. As the ability of hematopoietic tissues to produce phagocytes is of particular significance to mediate resistance to Listeria, the promotion ofbone marrow CFU-GM by MAPA may contribute to a rapid restoration of phagocyte numbers in infected sites, thus mitigating the course of infection.
The characterisation and uptake of paraquat in cultured baboon kidney proximal tubule cells (bPTC)
Authors: Machaalani R , Lazzaro V , Duggin G G
Published: April 2003

A primary culture of baboon proximal tubule cells (bPTC) was prepared and characterised using LLC-PK1 cells of proximal tubule origin and MDCK cells of distal tubule origin, as positive and negative references, respectively. The proximal tubular origin of the bPTC was determined by morphological studies, immunoperoxidase staining and the expression of proximal tubule markers alkaline phosphatase and gammaglutamyltransferase.

The hypothesis that paraquat (PQ) is transported by the bPTC was investigated. The cytotoxic threshold for PQ in these cells was determined and compared to the LLC-PK1 and MDCK cells. Furthermore, this study investigated the transport of the monovalent cation tetraethyl ammonium (TEA) and the polyvalent cation cimetidine in the bPTC and demonstrated their effect on the cellular uptake of PQ. The cytotoxic threshold of PQ in the bPTC, determined by cellular viability studies using the method of Trypan blue exclusion, is 0.05 mM at 2 h incubation. The LC50 after 24 his 76, 61 and 455 pM for the bPTC, LLC-PK1 and MDCK cells, respectively. This indicates that proximal tubule cells are more susceptible to PQ toxicity compared to distal tubule cells, which is consistent with clinical PQ toxicity where renal damage is found predominantly in the proximal renal tubules.

The cations PQ and cimetidine were actively transported by the bPTC. The uptake of PQ (0.05 mM) commenced after 15 min whereas cimetidine (0.5 mM) uptake was evident after 2 min. Furthermore, cimetidine was shown to compete with PQ for uptake in the bPTC. Coincubating PQ (0.05 mM) and cimetidine (0.5 mM) for 60 min resulted in an approximate 50% decrease in PQ uptake.

The cation TEA was not transported by the bPTC suggesting either a genetic mutation or complete absence of the transporter for TEA in the cells. The results suggest that PQ may be transported by the same cation transporter as cimetidine and not TEA, indicating PQ uptake in the bPTC to be via a polyvalent organic cation transporter.
Compartmental model for aluminium biokinetics
Authors: Nolte E , Beck E , Winklhofer C , Steinhausen C
Published: April 2003

An open compartmental model for describing aluminium biokinetics is presented with a central compartment consisting of transferrinand citrate-bound aluminium in blood plasma and interstitial fluid, and three peripheral compartments for organs, muscles and bones and the gastro-intestinal tract. The rate constants describing the transport of aluminium are normalized to an estimated plasma volume and do not depend on the size of the individual. Effects due to changes in compartmental sizes or to transport characteristics are described. The model is applied to biokinetics studies of a volunteer after i.v. administration and of Sprague-Dawley rats with different iron status and with nephrectomization after p.o. administration of 26Al.