bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer
Authors: Harrison DJ , Cantlay AM , Rae F. , Lamb D. , Smith Cad 
Published: December 2008

1 Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been associated with a number of apparently unrelated cancers, including lung cancer. Emphysema is a common lung disease often found concomitant with lung cancer. Both emphysema and lung cancer may result from chemical and oxidative damage caused by reactive species present in cigarette smoke or released from neutrophils recruited follow ing cigarette smoke induced injury. GSTM1 may protect against such damage through detoxification of cigarette smoke components. Polymorphism of this gene may thus influence susceptibility not just to lung cancer, but to other forms of lung disease. 2 Resection specimens from a group of 168 lung cancer patients were assessed for the presence of macro scopic centriacinar and panacinar emphysema. DNA was extracted from archival material and genotyped for the GSTM1 polymorphism using the polymerase chain reaction. A control group of 384 anonymous blood donations was used to determine the frequency of the GSTM1 gene deletion in a random control population. Reverse transcription on lung tissue was performed to investigate mRNA expression of GSTM1 and GSTM4. 3 In 57 lung cancer cases with no emphysema there was no association with homozygous deletion of the GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111 patients with emphysema and lung cancer there was an increase in the frequency of deletion (65%, P=0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases there was evidence of both centriacinar and panacinar emphy sema. The frequency of GSTM1 deletion was 70% (Odds ratio 2.11, 0.97 - 3.25). Both GSTM1 and GSTM4 mRNAs were expressed in lung tissue. 4 These findings suggest that GSTM1 has a general but rather small protective effect against toxicological injury in the lung which is not specific to cancer. This is of relevance in considering the health effects of exposure to a wide range of reactive chemicals in the environment.
Kinetic analysis of the intestinal iron absorption process in situ. The potential of vascularly autoperfused intestinal loops
Authors: Hunder G. , Osterloh K. , Schümann K. 
Published: December 2008

1 Blood sampling from mesenteric venules during absorption in situ is a useful tool to analyse intestinal absorption kinetics and prehepatic metabolism in different sections of the rat small intestine. By use of a micromanipulator, the method can be applied to the duodenum. This part of the small intestine shows the strongest adaptation of non-haem iron absorption to the demand for iron. 2 Iron absorption kinetics was linear in duodenal and jejunal segments. In iron-deficient animals, intestinal iron absorption capacity was increased in the duode num, while simultaneously determined galactose absorption showed no change. 3 In situ perfusion and cannulation of mesenteric venules in duodenal segments are described. The use of a micromanipulator permits varying the blood volume collected by changing the vertical angle between the cannula and the mesenteric vessel. 4 Intestinal iron absorption rates remained close to constant when blood flow rates were varied by a factor of about ten. Plasma concentrations of absorbed iron vs mesenteric blood flow rates followed a hyperbolic function, as the plasma concentration of absorbed iron in mesenteric venules increased to the same extent as the blood flow decreased. 5 As the plasma transferrin concentration did not change over the experimental period, the concentra tion of absorbed iron in the mesenteric plasma exceeded the iron-binding capacity of plasma trans ferrin at low blood flow rates. This observation shows that enhancement of intestinal iron absorption does not require a corresponding increase in plasma iron- binding capacity in the intestinal tissue. 6 Vascularly perfused gut loops were also used to measure prehepatic metabolism, which may influence organotropism of carcinogenic metabolites. Therefore, this type of preparation is likely to find a variety of toxicological applications.
Influence of solubility and permeant size on absorption and metabolism of xenobiotics in rabbit skin
Authors: Bast Gabriele E 
Published: December 2008

1 In order to obtain an understanding of the risks associated with dermal uptake of xenobiotics it is necessary to investigate the principles governing percutaneous absorption and metabolism. The sin gle-pass perfused rabbit ear served as a convenient model for the simultaneous study of absorption and metabolism of a variety of substances. We found: 2 When substances are applied in a lipophilic vehicle the permeation coefficient K P is notably decreased when the distribution coefficient (n-octanol/perfusion buffer (pH 7.4)) Poct. exceeds 2000. KP also decreases with increasing molecular weight. 3 Substances which are in the ionized state at pH 7.4 may have a higher permeation coefficient than would be expected from Poct. or by molecular weight. 4 The partition of a drug from the stratum corneum to the epidermal enzymes controls the extent of its metabo lism. However, substances with increased solubility at physiological pH are metabolized to a lesser extent than expected from their absorption rate.
Primary aromatic amines: their N-oxidative bioactivation
Authors: Hlavica P. , Golly I. , Lehnerer M. , Schulze J. 
Published: December 2008

There exists a diversity of pathways in mammalian cells serving to activate primary aromatic amines.1 N-Oxidative mixed-function turnover usually involves participation of the cytochrome P450 superfamily, while catalysis by the flavin-containing monooxy genases is restricted to a few amines capable of forming imine tautomers. Surprisingly, haemoglobin metabo lizes cytotoxic and carcinogenic arylamines via a monooxygenase-like mechanism, but peroxygenase activity is also operative.2 In extrahepatic tissues that exhibit only a low level of monooxygenases, peroxidative transformations, as are brought about by prostaglandin H synthase, myeloperoxidase or lactoperoxidase, predominate in amine activation. Non-mammalian peroxidases fre quently used as model systems include horseradish peroxidase and chloroperoxidase.3 Non-enzymatic, light-induced conversion of aromatic amines to free radical or N-oxy products proceeds either via direct photolysis of the nitrogenous com pounds or through attack by lipid-derived reactive intermediates generated during irradiation.4 The interplay of the various tissue-specific processes of arylamine activation serves to explain differences in susceptibility toward the biological actions of primary aromatic amines.
Biomonitoring exposure to environmental tobacco smoke (ETS): A critical reappraisal
Authors: Scherer G. , Richter E. 
Published: December 2008

1 The most frequently used biomarkers for exposure to environmental tobacco smoke (ETS) are cotinine and thiocyanate in body fluids, carboxyhaemoglobin in red blood cells (COHb) and carbon monoxide in the expired air. Although not ideal, cotinine in blood, saliva or urine is an established biomarker for ETS exposure within the past 1-3 days. Comparison with cotinine concentrations in cigarette smokers reveals that passive smokers take up less than 1/100 of the nicotine dose of smokers. 2 Biomonitoring data available for the ETS-related exposure to genotoxic substances comprise uptake of benzene, polycyclic aromatic hydrocarbons (PAH), aromatic amines, tobacco-specific nitrosamines (TSNA), electrophilic compounds giving rise to ur inary thioethers, mutagens causing urinary mutagenic activity and the formation of various DNA adducts. With the exception of TSNA, these biomarkers are related to chemicals occurring ubiquitously in the environment and in the food. As a consequence, the background levels in unexposed nonsmokers are high compared to the observed increases (if any) associated with ETS exposure. 3 Some markers of biological effects, which, by defini tion, are non-specific with regard to the underlying exposure, have also been investigated in relation to ETS exposure. These markers comprise cytogenetic effects, aryl hydrocarbon hydroxylase (AHH) induc tion, urinary hydroxyproline excretion and various factors indicative of cardiovascular risks. The avail able data suggest that passive smoking is associated with a small induction of placental AHH and also with effects on cardiovascular risk markers. The latter findings in particular may be confounded by other risk factors, which have been observed to be more frequent in passive smokers than in unexposed nonsmokers.
Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats
Authors: Kassa J. , Fusek J. 
Published: December 2008

1 The effect of pharmacological pretreatment (pyridos tigmine, benactyzine and trihexyphenidyle), desig nated Panpal, and antidotal treatment (the oxime HI- 6 plus benactyzine) in soman poisoning was investi gated in a rat model with on-line monitoring of respiratory and circulatory parameters.2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activ ity in diaphragm and various brain parts.3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acet ylcholinesterase activity in all brain parts studied.4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreat ment or antidotal treatment alone.5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman- poisoned rats without significant reactivation of brain acetylcholinesterase.
Environmental exposure to polycyclic aromatic hydrocarbons in Czech Republic
Authors: Vyskocil Adolf , Fiala Zdenek , Fialova Dana , Krajak Vladimir , Viau Claude 
Published: December 2008

1 Objectives of this study were (1) to compare concentra tions of individual polycyclic aromatic hydrocarbons (PAH) in air of polluted and nonpolluted area of Czech Republic during winter and summer periods and (2) to verify if urinary 1-hydroxypyrene (1-OHP), as sup posed practical biological marker, permits the assess ment of spacial and temporal variations in environmental PAH exposure. 2 The study population consisted of three groups: (1) a group of 22 physical exercise students who regularly train outside, from the university situated in a polluted town, spending 14 days in winter and 14 days in summer in 'non-polluted' mountains; (2) a control group of 22 residents from the town and (3) a control group of 18 residents from the mountains. 3 The total PAH concentrations (sum of 13 individual PAH) were 19.3 and 104.6 ng/m3 in town and in mountains, respectively, during summer and 86.6 and 261 ng/m3 during winter. 4 Median 1-OHP levels ranged between 0.03 and 0.13 μmol/mol creatinine for controls and between 0.04 and 0.12 μmol/mol creatinine for students. No relationship was found between pyrene levels in air and group means of urinary 1-OHP. Our results show that other factors (probably PAH in food) contribute in masking air pollution influence on urinary 1-OHP levels in subjects non-occupationally exposed to PAH.
Monoisopropylglutathione ester protects A549 cells from the cytotoxic effects of sulphur mustard
Authors: Lindsay Christopher D , Hambrook Joy L , Lailey Alison F 
Published: December 2008

1 The A549 cell line was used to assess the toxicity of sulphur mustard (HD), using gentian violet (GV) and neutral red (NR) dyes as indicators of cell viability. It was found that exposure to concentrations in excess of 40 ?M HD resulted in a rapid onset of toxicity. 2 The ability of monoisopropylglutathione ester (MIPE) to protect A549 cells against the effects of a 100 ?M challenge dose ofHD was determined using the NR and GV assays. It was found that MIPE (8 mM) could protect cells against the effects ofHD though MIPE had to be present at the time of HD challenge. Cultures protected with MIPE were two times more viable than HD exposed cells 48 h after HD challenge when using the GV and NR assays to assess viability. Observations by phase contrast microscopy of NR and GV stained cultures confirmed these findings. Addition of MIPE after previously exposing the A549 cultures to HD (for up to 5 min) maintained cell viability at 72% compared to 37% for unprotected cultures, after which time viability fell significantly so that at 10 min there was no difference in viability between the MIPE treated and untreated cultures. 3 Pretreating A549 cultures with MIPE for 1 h followed by its removal prior to HD challenge did not maintain cell viability. Treatment of cultures with HD for 1 h followed by addition of MIPE did not maintain the viability of the cultures, thus the window within which it was possible for MIPE to rescue cell cultures from the effects of HD was of short duration. 4 High performance liquid chromatography was used to determine the biochemical basis of the actions of MIPE. It was found that whilst intracellular levels of cysteine were increased up to 40-fold following treatment of A549 cell cultures with MIPE, levels of reduced glutathione did not rise. The lack of protection seen in cultures pretreated with MIPE for 1 h prior to HD exposure suggests that raising intracellular cysteine levels was not an effective strategy for protecting cells from the effects of HD. The protection observed is probably due to extra cellular inactivation of HD by MIPE.
Vipera palaestinae snake envenomations: experience in children
Authors: Paret G. , Ben-Abraham R. , Ezra D. , Shrem D. , Eshel G. , Vardi A. , Winkler E. , Barzilay Z. 
Published: December 2008

In Israel, Vipera palaestinae (V. palaestinae) is the most common venomous snake, accounting for 100 - 300 reported cases of envenomation every year. However, V. palaestinae snakebites in children have not been exten sively investigated. The demographic features, treatment and outcome of V. palaestinae envenomation in 37 children treated in two medical centers over a 9 year period were retrospectively reviewed. The victims age ranged from 2-18 years with a mean age of 8.9 years. Twenty-nine children were males and eight were females. Twenty-one patients resided in rural areas, and 16 children were living in urban areas. Twenty-three (63%) of the patients were bitten on the lower limb; Twelve (33%) on the upper limb, and two on the head or neck (4%). Using a grading scale of one to three from minimal to severe envenomation, 15 (40.5%), 15 (40.5%) and 7 (19%) patients had mild, moderate and severe envenomation, respec tively. Major complications of envenomation that were manifested after arrival consisted of compartment syn drome (two patients) and respiratory dysfunction (two patients). Specific monovalent antiserum for the treatment of V. palaestinae bite was given to 16 children (43%) of whom, four patients were in the severe group, seven and five in the moderate and mild groups respectively. No patient suffered a significant infection, tissue loss, permanent disability or death. We conclude that early ICU admission along with close monitoring and antivenom therapy is important in reducing morbidity and mortality in children systemically envenomed by V. palaestinae.
Behavioural and functional neurotoxicological changes caused by cadmium in a three-generational study in rats
Authors: Nagymajtényi L. , Schulz H. , Dési I. 
Published: December 2008

1 Three consecutive generations of Wistar rats were orally treated by gavage with 3.5, 7.0 or 14.0 mg/kg cadmium (in form of cadmium chloride diluted in distilled water) over the period of pregnancy, lactation and 8 weeks after weaning. 2 Behavioural (open field behaviour) and electrophysio logical (spontaneous and evoked cortical activity, etc.) parameters of male rats from each generation were investigated at the age of 12 weeks. 3 The main behavioural outcomes were change in vertical exploration activity (rearing) and increased exploration of an open field centre. The spontaneous and evoked electrophysiological variables showed dose- and generation-dependent changes (increased frequencies in the electrocorticogram, lengthened latency and duration of evoked potentials, etc.) signalling a change in neural functions. 4 The data show that low-level, multigeneration expo sure to inorganic cadmium can affect functions of the nervous system. This suggests that cadmium exposed human populations may be at risk of developing nervous system disorders.
Effects of quercetin on drug metabolizing enzymes and oxidation of 2', 7-dichlorofluorescin in HepG2 cells
Authors: Musonda CA , Helsby N. , Chipman JK 
Published: December 2008

1 The effects of quercetin on drug metabolising enzymes and oxygen radicals were studied in human HepG2 cells. 2 Cytotoxicity of quercetin in HepG2 cells was seen at 50 μM and above as evaluated by lactate dehydrogen ase (LDH) leakage, neutral red (NR) uptake, and 3-(4,5- dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bro mide (MTT) reduction. 3 Quercetin inhibited activity of human cytochrome P- 450 towards ethoxycoumarin and ethylresorufin at relatively low substrate concentrations (0.1 μM and above). 4 In comparison to induction by the positive control (β- naphthoflavone; 1.0 μM), quercetin did not signifi cantly induce the metabolism of ethoxycoumarin or glutathione-S-transferase (GST) protein or activity. 5 Response elements for human CYP1A1, GSTλa, xenobiotic response element (XRE), fos, HSP70, CRE, p53, NFκB and DNA damage (GADD) in HepG2 cells were not activated by quercetin. 6 Quercetin exhibited antioxidant activity in HepG2 cells as evidenced by its ability to inhibit the oxidation of the fluorochrome dichlorofluorescin. 7 The results indicate a range of potential beneficial effects of quercetin with respect to the influence on carcinogen-metabolising enzymes, scavenging of re active oxygen species and a lack of stress response in HepG2 cells.
Haemoperfusion treatment in pigs experimentally intoxicated by paraquat
Authors: Yang TS , Chang YL , Yen CK 
Published: December 2008

1 Because of their similarity in renal morphology and physiology to humans, domestic pigs (gilts, 70 kg) were bolus treated by intramuscular injection of 74,17, and 6 mg kg-1and by oral loading (70 mg kg-1n=4) of paraquat. The concentration peak of plasma paraquat was reached at 1.5 - 2.5 h. Renal clearance of paraquat rose to its maximum at 5 - 6 h after intoxication and then sharply decreased indicating renal failure. All the intoxicated pigs died.2 An additional 10 gilts were also orally treated with 70 mg kg-1paraquat but received haemoperfusion from 2 h post intoxication for either 2 h (n=6) or 6 h (n=4). The 2 h haemoperfusion resulted in a 5.1% toxin removal but failed to save any of six poisoned pigs. Prolonged 6 h haemoperfusion successfully rescued three out of four intoxicated pigs.3 The plasma paraquat concentrations of the three surviving pigs were above 2 mg l-1at 10 h post intoxication. This level is not only similar to those of untreated animals that died later, but also well beyond the suggested limit for survival of poisoned patients.4 Pigs proved to be a good animal model for studies in paraquat poisoning and/or haemoperfusion. It is also suggested that early haemoperfusion is effective in treating paraquat poisoning even in very severe cases due to its possible detoxicating effect in addition to toxin removal.
Subchronic toxicity studies of 3-Methyl-1- butanol and 2-Methyl-1-propanol in rats
Authors: Schilling K. , Kayser M. , Deckardt K. , Küttler K. , Klimisch H-J. 
Published: December 2008

1 90-day subchronic toxicity studies with 3-methyl-1- butanol (MEB) and 2-methyl-1-propanol (MEP) were performed on rats to evaluate the toxicological profile of the compounds under conditions of drinking water studies, to identify the potential target organs, and to determine no-observable-adverse-effect-levels (NOAELs) respective of the substances. The test substances were administered to groups of 10 male and 10 female Wistar rats in drinking water at concentrations of 0, 1000 p.p.m. (about 80 mg/kg/d), 4000 p.p.m. (about 340 mg/kg/d) and 16 000 p.p.m. (about 1250 and 1450 mg/kg/d of MEB and MEP respectively). 2 16 000 p.p.m. was found to be the maximal concentra tion for both alcohols applicable to rats in drinking water. Higher concentrations had an influence on palatability and could thus not be tested in drinking water studies. 3 At 16 000 p.p.m. MEB a marginal increase in the red blood cell count as well as a slight decrease in the mean corpuscular volume and the mean corpuscular hemo globin content was observed in males only. These changes are considered to be treatment-related, although the toxicological significance of these find ings is unclear. No other substance-related effects were found on body weight (b.w.), mortality, various parameters of clinical chemistry, organ weights, gross pathology and histopathology. 4000 p.p.m. MEB did not cause any substance-induced changes. Therefore, the NOAEL of MEB was defined as 4000 p.p.m. for male and 16 000 p.p.m. for female rats under condi tions of oral application via drinking water. 4 MEP concentrations up to and including 16 000 p.p.m. did not induce any signs of toxicity and were therefore defined as the NOAEL respective of this substance for rats under conditions of drinking water application.
Test Results and What They Mean
Authors: Woolbright William J. 
Published: December 2008

Part of the responsibility of a reading therapist is to report to the parents the results of specialized programs developed for their children. Whether the report is made in person or sent to the parents or teachers of the children, there can be confusion or misunderstanding when grade-level scores are used. Over a period of time, and after a review of numerous parent conferences and discussions with local school administrators and teachers, the following report was prepared by the Academic Achievement and Learning Group, Los Angeles, California, to better communicate with parents and school personnel who are concerned about students' work in remedial reading.
The ADHD Conundrum
Authors: Bender William N. , McLaughlin Phillip J. 
Published: December 2008

Introduction to the special series on attention-deficit/hyperactivity disorder Professionals working within special and remedial education are often concerned about the specific nature of attention-deficit/hyperactivity disorders (ADHD) and how to both manage ADHD students in the classroom and provide appropriate and successful educational intervention. In response to these concerns, this issue of Intervention in School and Clinic is devoted entirely to the topic of ADHD. The guest editors of this issue, William Bender and Phillip McLaughlin, of the University of Georgia, have assembled an outstanding list of authors to write about the most prevalent issues in meeting the needs of the student with ADHD. I am pleased to devote this issue of Intervention to this important area.—GW