bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presentation of poisoned patients to accident and emergency departments in the North of England
Authors: Thomas Shl , Bevan L. , Bhattacharyya S. , Bramble MG , Chew K. , Connolly J. , Dorani B. , Han KH , Horner JE , Rodgers A. , Sen B. , Tesfayohannes B. , Wynne H. , Bateman DN 
Published: December 2008

1 A 12 week prospective survey of all patients of any age with confirmed or suspected poisoning presenting to six accident and emergency departments in the North East of England was performed to establish the local incidence and patterns of presentation of poisoning. 2 945 episodes of poisoning involving 852 patients were recorded representing approximately 1.2% of all A&E presentations and suggesting an annual attendance rate of 2.7 per 1000 persons per year. 3 Attendance rates varied threefold between hospitals and were similar in males and females overall; between the ages of five and 14 attendances were more common in females (1.9 vs 0.6/103/y) while between 0 and 4 y (3.1 vs 2.4) and 25 and 34 y (3.9 vs 2.9/103/y) they were more common in males. 4 The median interval between poisoning and presenta tion was 2 h (mean 4.1 h) and only 19% of cases presented within 1 h. Presentation was most common between Friday evening and Tuesday morning and in the late afternoon and evening. 5 6% of the patients presented more than once with poisoning during the study period and 37% had a past history of deliberate self-harm. The most common poisons involved were paracetamol (43%), opioids (15%) and benzodiazepines (15%). 6 The study illustrates the frequency of presentations of poisoning to A&E departments. The high rate of poisoning in young men and the increasing use of paracetamol are particular causes for concern.
Evaluating clinical case report data for SAR modeling of allergic contact dermatitis
Authors: Gealy Robert , Graham Cynthia , Sussman Nancy B , Macina Orest T , Rosenkranz Herbert S , Karol Meryl H 
Published: December 2008

Clinical case reports can be important sources of information for alerting health professionals to the existence of possible health hazards. Isolated case reports, however, are weak evidence of causal relationships between exposure and disease because they do not provide an indication of the frequency of a particular exposure leading to a disease event. A database of chemicals causing allergic contact dermatitis (ACD) was compiled to discern structure-activity relationships. Clinical reports repre sented a considerable fraction of the data. Multiple Computer Automated Structure Evaluation (MultiCASE) was used to create a structure-activity model to be used in predicting the ACD activity of untested chemicals. We examined how the predictive ability of the model was influenced by including the case report data in the model. In addition, the model was used to predict the activity of chemicals identified from clinical case reports. The following results were obtained: • When chemicals which were identified as dermal sensitizers by only one or two case reports were included in the model, the specificity of the model was reduced. • Less than one half of these chemicals were predicted to be active by the most highly evidenced model. • These chemicals possessed substructures not pre viously encountered by any of the models. We conclude that chemicals classified as sensitizers based on isolated clinical case reports be excluded from our model of ACD. The approach described here for evaluating activity of chemicals based on sparse evidence should be considered for use with other endpoints of toxicity when data are correspondingly limited.
A search for possible cytogenetic effects of low frequency vibrations in cultured human lymphocytes
Authors: Khalil Ahmad M , Qassem W. 
Published: December 2008

1 Acute cytogenetic effects expressed as sister-chroma tid exchanges (SCE) in peripheral blood lymphocytes were investigated after in vitro exposure to low vibration regimes (5 - 30 Hz, at 0.1 cm amplitude) for 20 min intervals and compared to non-vibrated control cultures. 2 There was no significant (P<0.05) increase in the range of SCE incidence at any vibration frequency compared to the mean value of control; 6.88 ± 0.11 to 7.97±0.22 versus 6.83±0.86, respectively. 3 When cultures were incubated for 1 h in the presence of 0.5 μg ml-1 mitomycin C (MMC; the positive control) significant elevations in the SCE frequency were observed (19.81 ± 0.67), indicating the sensitivity of the system to in vitro SCE induction. 4 Other cell parameters, such as mitotic index and cell proliferation index were statistically similar in the experimental cultures and the negative control. 5 The observed differences in the investigated end points are considered within those typically found in vitro. This suggests no relation between low frequency vibrations and cytogenetic effects.
HFA-134a (1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon reproductive performance, development and maturation of rats
Authors: Alexander DJ , Libretto SE , Adams MJ , Hughes EW , Bannerman M. 
Published: December 2008

1 HFA-134a was administered to AHA rats by snout-only inhalation for 1 h daily to assess the effects of treatment on reproduction and development. 2 In a fertility study, rats were exposed to atmospheres of 2500, 10000 or 50000 p.p.m. HFA-134a throughout gametogenesis, mating, pregnancy and lactation. 3 In a peri- and post-natal study, rats were exposed to HFA-134a from days 17 to 20 of pregnancy and days 1 to 21 post partum to atmospheres of 1800, 9900 or 64 400 p.p.m. 4 The only treatment-related effect was a slight reduc tion in body weight gain of males of the treated parental generation at 50 000 p.p.m. (fertility study). 5 In neither study were there any adverse effects of HFA- 134a on the reproductive performance of treated animals or on the development, maturation or reproductive performance of up to two successive generations.
The effect of sulphur mustard on glutathione levels in rat lung slices and the influence of treatment with arylthiols and cysteine esters
Authors: Langford AM , Hobbs MJ , Upshall DG , Blain PG , Williams Faith M 
Published: December 2008

1 Sulphur mustard reacts directly with benzenethiols and cysteine esters in aqueous medium. 2 Benzenethiols diffuse into lung slices in short term culture. 3 Treatment of lung slices in short term culture with benzenethiols does not protect cellular glutathione from conjugation with sulphur mustard. 4 Following uptake of cysteine ester into lung slices cysteine is elevated but this does not protect cellular glutathione from sulphur mustard.
Protein-energy malnutrition and oxidative injury in growing rats
Authors: Rana Satyawati , Pal Sodhi Chhinder , Mehta Saroj , Vaiphei Kim , Katyal Ranjan , Thakur Sarita , Satish Kumar Mehta  
Published: December 2008

1 Weaning rats were fed ad libitum isocaloric diets containing 5% and 20% casein based proteins. 5% protein diet was protein deficient diet. Pair fed rats with the 5% protein group were maintained simulta neously on 20% protein diet but the amount restricted to the amount taken up by PEM group. 2 Glutathione, antioxidative enzymes, lipid peroxida tion and histopathological studies in liver and only glutathione and antioxidative enzymes in blood were carried out. 3 Rats fed the 5% protein diet developed a severe protein energy malnutrition (PEM) whereas those on pair-fed diet developed mild to moderate PEM. 4 Glutathione related thiols, superoxide dismutase, glutathione peroxidase, catalase and glutathione-S- transferase with (1 Chloro 2,4-dinitro benzene (CDNB) substrate) were decreased in liver with concomitant increase of lipid peroxidation in severe PEM. In blood glutathione, glutathione peroxidase and catalase were decreased while superoxide dismutase was increased in severe PEM group. 5 Mild to moderate PEM (pair-fed group) also resulted in similar changes in liver except glutathione peroxidase, lipid peroxidation in liver and superoxide dismutase in blood. 6 Hepatic injury was detectable only in the severe PEM group. 7 Oxidative-stress and hepatic injury occurred in severe PEM and to a lesser degree in mild to moderate PEM.
Effects of mode of inhalation of carbon monoxide and of normobaric oxygen administration on carbon monoxide elimination from the blood
Authors: Levasseur L. , Galliot-Guilley M. , Richter F. , Scherrmann JM , Baud FJ 
Published: December 2008

1 The half-life of carbon monoxide (CO) in blood was studied retrospectively in 26 fire victims and in 19 cases of CO poisoning. Normobaric oxygen therapy was administered via mechanical ventilation in 19 fire victims, and by facial mask to the rest of the casualties. 2 Arterial pH was significantly lower (P < 0.05) and PaO2 significantly greater (P<0.01) in the mechanically ventilated fire victims compared to the spontaneously breathing fire victims. 3 The blood CO half-lives were 91 ± 38 min for the 26 fire victims and 87±40 min for the 19 pure CO intoxica tions. 4 The blood CO half-lives were 92 ± 40 min for the 19 mechanically ventilated fire victims and 87 ± 37 min for the 26 spontaneously breathing subjects. 5 We conclude that the elimination of CO from blood was a slow process with no significant effects on the blood CO half-life of either the cause of the CO poisoning or the mode of normobaric oxygen therapy. These data suggest that enhancement of the elimination of carbon monoxide by normobaric oxygen in both pure CO poisoning and fire victims is more difficult to achieve and more complex than has previously been reported.
Assessment of aspects of the toxicity of Clostridium perfringens E-toxin using the MDCK cell line
Authors: Lindsay Christopher D 
Published: December 2008

1 The epithelial Madin Darby Canine Kidney (MDCK) cell line was used to study the toxicity of ∈-toxin from Clostridium perfringens. The epithelial MDCK cell line is known to be sensitive to ∈-toxin of Clostridium perfringens and to investigate its mechanism of action, the neutral red assay has been used to determine the viability of cultures of this cell line. 2 Comparison of the LC 50s obtained at 34°C and 0°C showed that the lethality of ∈-toxin was reduced by 18- fold at the lower temperature. The effect of tempera ture on ∈-toxin lethality is unlikely to be due to reductions in membrane fluidity for the addition of Ca2+ or Mg2+ (2 mM) to buffer containing toxin was without effect. Varying the pH of the toxin-containing buffer from 6.9 to 8.7 did not increase the lethality of the toxin, though the most acidic pH used (5.8) was found to potentiate its action on MDCK cells. 3 The effect of inhibiting endocytosis on the lethality ofe toxin was also investigated by incubating cultures of MDCK cells with and without sodium azide over a range of concentrations of toxin. The co-administra tion of sodium azide did not reduce the toxicity of ∈ toxin, suggesting that energy-dependent uptake pro cesses such as endocytosis were unlikely to be involved in its mechanism of action. The results are, however, consistent with known receptor-based me chanisms of uptake and with other mechanisms of internalisation across the plasma membrane. ∈-toxin thus interacts with cell surfaces by a temperature sensitive mechanism potentiated by low pH.
Effects of catecholamines and diazepam in chloroquine poisoning in barbiturate anaesthetised rats
Authors: Buckley Nicholas A , Smith Anthony J , Dosen Peter , O'Connell Dianne L 
Published: December 2008

The recommended treatment of human chloroquine poisoning is diazepam and adrenaline but neither has been evaluated in controlled clinical trials. We investi gated whether diazepam provided any added benefit over barbiturate anaesthesia and whether the protective effect of catecholamines in chloroquine poisoning was mediated through alpha or beta receptor stimulation.Rats, anaesthetised with thiobutobarbitone had a continuous intravenous infusion of 3 mg/kg/min of chlor oquine. This caused a steady decline in pulse rate and blood pressure. When diazepam (3 mg/kg iv) was admi nistered 5 -10 min later, heart rates decreased at a faster rate (P=0.005), blood pressure was consistently lower (P=0.01) and there was a shorter time to arrhythmias and death (P < 0.05). Adrenergic agents were given by titration to attempt to maintain mean blood pressure > 75 mmHg. Compared with the phenylephrine (selective alpha agonist) group, the group treated with isoprenaline (selective beta agonist) had faster heart rates which decreased more slowly (P < 0.0001), higher blood pressure (P=0.005) and longer time to arrhythmias and death (P=0.005). Adrenaline and noradrenaline had intermedi ate effects. Thus beta agonist effect appears to explain the beneficial effects of adrenaline but alpha agonist activity may be harmful. This animal work suggests that a combination of barbiturate anaesthesia and isoprenaline may be better than the diazepam and adrenaline in combatting the effects of chloroquine.
Interspecies differences in enzymes reacting with organophosphates and their inhibition by paraoxon in vitro
Authors: Kaliste-Korhonen E. , Tuovinen K. , Hänninen O. 
Published: December 2008

1 Inhibition of cholinesterases (ChE) and carboxyles terases (CaE) by paraoxon (Px) was studied in vitro in the serum, liver, lung and muscle of mouse, guinea pig, rabbit and man (serum only). Moreover, the role ofPx hydrolyzing enzyme (Pxase) in the detoxification of Px was studied by inhibiting its activity with EDTA. 2 The ChE and CaE activities as well as their sensitivity to Px varied in different tissues and species. The ChEs were more sensitive than CaEs to Px except in the liver. The CaE activity in human and rabbit sera was low and resistant to Px, indicating that it may have a minor importance for the binding of Px. 3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and rabbit sera during 24 h. In mouse, also the CaE activity was recovered. The presence of EDTA in the incubation medium prevented this reactivation indicating that Pxase takes part in the reactivation process. 4 In rabbit, the serum Pxase activity was very high suggesting a good Px detoxifying capacity of the rabbit serum. 5 The results show that amounts and sensitivities of esterases to OPs in rodents may markedly differ from that in man. Possible species-related differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing activity should be taken into the con sideration, when animal data are extrapolated to man.
Effects of pyridostingmine on acetylcholinesterase in different muscles of the mouse
Authors: Lintern Maxine C , Smith Margaret E , Ferry C Brian 
Published: December 2008

1 Pyridostigmine bromide was administered subcuta neously in mice, in a dose of 0.4 or 2.0 ?moles/kg, and the activity of the predominant (G1, G4, and A12) molecular forms of acetylcholinesterase were exam ined in diaphragm, extensor digitorum longus (EDL), and soleus muscles at 3 h, 6 h, 24 h and 5 days.2 In diaphragm, no effect was apparent after the low dose, but after the high dose there was a reduction in activity of the functional A12 form at 24 h, followed by an increase which had overshot the control level at 5 days.3 In the fast EDL, after the low dose, all three molecular forms were decreased at 3 h, but had returned to normal by 6 h. This effect was not apparent after the high dose.4 In the slow soleus the low dose caused a significant increase in total enzyme activity at 5 days, but the high dose caused significant increases in all molecular forms at 3 hours.5 Thus pyridostigmine had delayed effects on the levels of acetylcholinesterase. The three muscles displayed different sensitivities to the drug, but the changes were consistent with initial inhibition of the activity leading to down-regulation of the enzyme followed by up- regulation, which could overshoot the normal levels.
The effects of multiple low doses of organophosphates on target enzymes in brain and diaphragm in the mouse
Authors: Williams Faith M , Charlton C. , de Blaquière Gail E , Mutch Elaine , Kelly SS , Blain PG 
Published: December 2008

1 Multiple low doses of the direct acting organopho sphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and ecothiopate than for mipafox.2 Ecothiopate did not inhibit brain acetylcholinesterase but there was a small increase in activity.3 Mipafox also had a cumulative inhibitory effect on brain neuropathy target esterase.4 These results have particular implication for the use of multiple low doses of organophosphates occupation- ally by man.
Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation
Authors: Dalsenter PR , Faqi AS , Webb J. , Merker H-J. , Chahoud I. 
Published: December 2008

1 Reproductive toxicity and toxicokinetics of lindane during lactation were studied. For the reproductive toxicity study the dams were treated with a single dose of 6 mg/kg on day 9 or 14 of lactation, or with 1 mg/kg on days 9 to 14 of lactation. The male offspring were investigated at puberty and adulthood. For the toxicokinetic study, two groups of dams were treated with 6 mg/kg on day 9 or 14 of lactation. The concentration of lindane was measured in maternal plasma and milk, as well as in male offspring organs. 2 At adulthood, testicular weight and the number of sperm and spermatids were significantly reduced in all treated groups. 3 The testosterone level of the groups treated with 6 mg/ kg was significantly reduced to approximately 50% at puberty as well as in adulthood. In the group treated with 1 mg/kg, the testosterone level was in both age periods reduced, however, only at puberty was the reduction statistically significant. 4 The concentration oflindane in the testis was similar to that found in brain and was half the concentration found in the liver. 5 Histologically some areas of the testis exhibited distinct alterations ranging from small changes to a pronounced effect. 6 Exposure to lindane during lactation induces repro ductive hazards to male offspring rats which are detectable at adulthood.
Covert poisoning with difenacoum: clinical and toxicological observations
Authors: McCarthy PT , Cox AD , Harrington DJ , Evely RS , Hampton E. , Al-Sabah AI , Massey E. , Jackson H. , Ferguson T. 
Published: December 2008

1 The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 year old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described. 2 Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarbox yprothrombin (DCP) unexpectedly increased. 3 Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1). 4 Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion ofthe vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.
Effect of perinatal vitamin A or retinoic acid treatment (hormonal imprinting) on the sexual behavior of adult rats
Authors: Csaba György , Gaál Annamária 
Published: December 2008

Single neonatal treatment with vitamin A (retinol) dramatically reduced the sexual activity of adult male rats. In females there was a significant decrease in the Meyerson index and a non significant decrease in the lordosis quotient. The effect of three perinatal treatments (at the first, third and fifth day) with all-trans retinoic acid was much weaker, causing only a significant increase in the time of the first ejaculation in males and non- significant decrease in the lordosis quotient of females. The experiments call attention to the false imprinting provoking effect of materials acting on members of the steroid receptor superfamily with possible human health aspect.
Induction of cytochrome P450 3A by retinoids in rat hepatocyte culture
Authors: Jurima-Romet M. , Neigh S. , Casley WL 
Published: December 2008

1 Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all- trans-retinoic acid, 9- cis-retinoic acid, 13- cis-retinoic acid or fenreti nide.2 Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold in hepatocytes treated with the retinoids compared to control cultures.3 CYP1A1 and CYP1A2 RNA levels were only slightly affected or unaffected by the retinoids.4 The induction of CYP3A by these therapeutically- useful retinoids suggests that they may share a common mechanism for accelerated drug catabolism and acquired clinical resistance.
The efficacy of calcium gluconate in ocular hydrofluoric acid burns
Authors: Beiran Itzchak , Miller Benjamin , Bentur Yedidia 
Published: December 2008

1 Although calcium gluconate (CG) is recommended in the treatment of hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and controlled human or animal studies are limited. The study's objective is to compare the efficacy of 1% CG and normal saline irrigation for the treatment of HF eye injury in animals. 2 0.05 ml 2% HF was instilled to anesthetized rabbit's eyes. One minute later, four treatment groups were studies: (1) irrigation with normal saline followed by topical antibiotics, corticosteroids and cycloplegics for 48 h ( n=10); (2) irrigation with 1% CG followed by the same topical treatment ( n=9); (3) as group 1 and 1% CG drops over 48 h ( n=10); (4) as group 3, and injection of 1% CG subconjunctivally after irrigation ( n=9). 3 Corneal erosion area, corneal haziness, conjunctival status, vascularization (pannus) and acidity were assessed before injury, immediately after intitial treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein staining. 4 Conjunctival pH dropped from 6.0 - 6.5 to 2.5 - 3 after injury and increased to 6 - 6.5 after irrigation. Corneal erosion: smaller in groups 2, 3, significantly so at 2 days, but not different at 14 days. Corneal haziness: more severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2 - 4 eyes in each group. 5 It seems that for HF injury 1% CG did not have any significant advantage over saline irrigation and topical treatment only. It might have some initial and temporary effect on healing process especially that involving erosion. Given subconjunctivally, 1% CG may be toxic and worsens clinical outcome.