bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of N-Acetyl Transferase in a Human Monocytic Cell-Line, U937
Authors: Kelly S.L. , Sim E. 
Published: December 2008

1 N-acetyl transferase (NAT) catalyses the acetylation of arylamine and hydrazine drugs and other xenobiotics. The activity of one isozyme (polymorphic NAT) varies amongst indiviudals but the other (monomorphic NAT) does not.2 The human monocytic cell-line U937 transcribes the gene for monomorphic N-acetyl transferase.3 Although the gene for polymorphic N-acetyl transferase is present in these cells, its expression is not detected.4 It is concluded that U937 cells are a useful model for studying the metabolism of arylamines and hydrazines by human monomorphic N-acetyl transferase.
Quantitation of Albumin and Alpha-1-Acid Glycoprotein in Human Cervical Mucus
Authors: Salas Herrera I.G. , Pearson R.M. , Turner P. 
Published: December 2008

1 Concentrations of albumin and alpha-1-acid glycoprotein (AGP) in human cervical mucus have been measured by a radial immunodiffusion technique.2 The cervical mucus samples were obtained from women on combined oral contraceptives (Group A) and from women not taking this medication (Group B). In group A the mean level of albumin was 75.6 (range 22-198) mg 1-1and for AGP 6.5 (range 3-12) mg 1-1. In group B the mean level of albumin was 72.9 (range 22-148) mg 1-1and for AGP 6.6 (range 3-14) mg 1-1.3 The levels of albumin and AGP in cervical mucus were less than 1% of the concentration in serum and were not affected by combined oral contraceptives.4 The clinical and toxicological consequences of these observations, in terms of the disposition of drugs and other chemicals in the female genital tract, await elucidation.
Absence of Polymorphism of Sparteine Oxidation in the South African Venda
Authors: Sommers De K. , Moncrieff J. , Avenant J.C. 
Published: December 2008

1 This study has found no occurrence of poor metabolism of sparteine within a South African Venda populaton of 97 subjects. 2 On the basis of MR (metabolic ratio) the mean and distribution of the results are very similar to those found in Ghanaians.5,14 3 The distribution is also similar to that for fast metabolizers in Caucasians.14 4 It is concluded that different P450 cytochromes are responsible for immediate oxidation of debrisoquine and sparteine, but that both may be activated by the same P450 reductase.
A Pilot Study on the Urinary Excretion of Porphyrins in Human Populations Chronically Exposed to Arsenic in Mexico
Authors: García-Vargas Gonzalo G. , García-Rangel Adalberto , Aguilar-Romo Manuel , García-Salcedo Javier , del Razo Luz Maria , Ostrosky-Wegman Patricia , Cortinas de Nava Cristina , Cebrián Mariano E. 
Published: December 2008

1 The aim of this pilot study was to investigate if the porphyrinuria produced by arsenic in rodents was present in humans chronically exposed to arsenic via drinking water. 2 The concentrations of uroporphyrin, coproporphyrin and total arsenic in urine were compared between 21 individuals exposed to arsenic in their drinking water (0.390 mg 1-1) and 19 controls exposed to 0.012 mg 1-1. 3 Arsenic-exposed individuals had significantly higher total arsenic concentrations in their urine than the control group. No increase in urinary porphyrin excretion was found in exposed individuals. However, an inversion of the coproporphyrin/uroporphyrin (COPRO/ URO) ratio was observed in most exposed individuals. This inversion was caused both, by a decrease in coproporphyrin excretion and an increase in uroporphyrin excretion. 4 No demonstrable correlations between porphyrin excretion, the COPRO/URO ratio and total arsenic concentration in urine were found in exposed individuals.
Recovery of Biochemical Changes Induced by 1, 2-Dichloro propane in Rat Liver and Kidney
Authors: Trevisan Andrea , Troso Ornella , Maso Stefano 
Published: December 2008

1 Biochemical changes in male, Wistar rats, treated with different doses of 1,2-dichloropropane (50-500 mg kg-1 body weight), were investigated at the end of a 4-week treatment and after a 4-week recovery period. 2 The behaviour of Phase I and Phase II metabolic steps and of the angiotensin converting enzyme activity of the renal proximal tubule brush border were determined. 3 Phase II is more affected by the solvent than Phase I metabolism, and liver metabolism is more affected than the kidney. 4 Angiotensin converting enzyme activity from the proximal tubule brush border appears to be the most sensitive parameter of kidney involvement during treatment. 5 After a 4-week recovery period all the metabolic indices together with angiotensin converting enzyme activity have returned to normal. Only liver reduced glutathione content shows a slight, but significant, increase for the highest dose (500 mg kg -1 body weight). 6 The results show that the biochemical changes induced in liver and kidney by 1,2-dichloropropane are reversible.
Considerations Regarding the Development of Individual Non-clinical Test Strategies in the European Community
Authors: Günzel P. , Bass R. 
Published: December 2008

The wish of pharmaceutical companies to be given the most binding possible preclinical test programmes for a new product, and the tendency of authorities to regulate to a great extent the preclinical testing of new drugs (especially at a multinational level), has led to differing requirements and practices in preclinical testing in different areas of the world. These differing requirements and practices have of necessity brought in their wake varying scientific criteria, with particular regard to animal protection, ethical standards, as well as imposing apparently unjustified extra financial costs. In order to improve this situation, the development of drug-specific preclinical test strategies is proposed in a drafted E. C. Note for Guidance, which incorporates already existing drug-testing guidelines and method recommendations. This draft Note for Guidance points to general methods of analysing problems and reaching decisions and thus appears to be worthy of recommendation as practical and desirable. It requires the co-operation of drug producers and supervisory authorities at a high scientific and ethical level. With regard to the state-of-the art and the socio-political background, the fulfilment of these requirements would appear not only to be appropriate but also imperative. To put them into practice would contribute enormously to the improvement of drug development and to de-emotionalization of the public debate. Therefore, comments on these draft guidelines from societies and associations are urgently sought and awaited with keen interest.
Chloracne Caused by Ingestion of Olive Oil Contaminated with PCDDs and PCDFs
Authors: Rodriguez-Pichardo A. , Camacho F. , Rappe C. , Hansson M. , Smith A.G. , Greig J.B. 
Published: December 2008

1 All members of a Spanish family (father, mother and six children) developed chloracne. 2 The causative agent was found to be the family's stock of olive oil, which had become contaminated with polychlorinated dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), pentachlorophenol, and hexachlorobenzene. 3 The more highly chlorinated PCDDs, in particular octachlorodibenzo- p-dioxin, were the predominant congeners in the oil. 4 Three members of the family exhibited either an overt or a sub-clinical disturbance of kidney function. The father also had a chronic respiratory problem. These changes could not be unequivocally attributed to the PCDDs. 5 Experimental toxicity of the oil was limited to the development of an hepatic porphyria in mice. 6 A serum sample, taken 5 years after consumption of the oil ceased, contained high levels of the PCDDs and PCDFs. Extrapolation back to ingested dose was used to validate dosage estimates. 7 The use of toxicity equivalence factors (TEFs) provided estimates of cumulative dosage to produce chloracne as 0.13-0.31 μg 2378-TCDD kg-1 (using EPA TEFs) or 6.7-16 μg 2378-TCDD kg-1 (using Nordic/NATO TEFs). 8 This is the first incident in which human toxicity is related primarily to ingestion of PCDDs and for which estimates of dosage can be made.
Effect of Activated Charcoal on the Absorption of Amiodarone
Authors: Kivistö Kari T. , Neuvonen Pertti J. 
Published: December 2008

1 The ability of activated charcoal to prevent the absorption of amiodarone was studied in 18 healthy volunteers, divided into three groups of six subjects. 2 All subjects were administered a single dose of 400 mg amiodarone; one group ingested the drug with water only (control) and the second with 25 g of activated charcoal as a water suspension. The subjects in the third group were given 25 g of charcoal immediately after the 1.5 h blood sample. 3 The extent of amiodarone absorption was reduced by about 98% by simultaneously administered charcoal ( P < 0.001); taking charcoal 1.5 h after amiodarone still resulted in a 50% reduction in amiodarone bioavailability ( P < 0.05). 4 These results indicate that activated charcoal should be effective in preventing amiodarone absorption in acute poisoning.
Hyperphosphataemia and Hypocalcaemia Induced by Hypertonic Phosphate Enema - An Experimental Study and Review of the Literature
Authors: Grosskopf Itamar , Graff Eran , Charach Gideon , Binyamin Gideon , Spinrad Sara , Blum Ilana 
Published: December 2008

1 The study objective was to determine the hyperphosphataemic and hypocalcaemic effect of hypertonic phosphate enema. The study was conducted in a department of Internal Medicine at a University Medical Center. 2 Fourteen patients were studied. Patients' mean age (± s.d.) was 78.5 ± 9 years. The creatinine clearance was 48.2 ± 17.4 ml min-1 (mean ± s.d.). 3 500 ml (approx. 7 ml kg-1) of Fleet enema (FE - Na2HPO4.7H 2O 224 mmol l-1 and NaH2PO4.H 2O 1160 mmol l-1) were administered to each patient. Blood was drawn before FE administration and ½, 1, 3, 5, 12 and 24 h thereafter. Serum was analysed for levels of inorganic phosphorus and for calcium. 4 The serum inorganic phosphorus level rose from 1.01 ± 0.3 mmol l-1 to 1.4 ± 0.5 mmol l-1 ( P = 0.001) 1 h after FE was administered. Serum calcium decreased from 2.32 ± 0.12 mmol l-1 to 2.12 ± 0.1 mmol l-1 ( P < 0.001) 12 h after FE was administered. 5 We conclude that FE carries a potential risk for acutely ill elderly patients. To avoid untoward effects due to hyperphosphataemia and hypocalcaemia, the phosphate load must be adjusted to the patient's renal function, i.e. enema volume is to be lowered when phosphate concentration is high, so that if renal function is compromised the amount of phosphate absorbed does not exceed renal excretion capacity.
An Acute Mercuric Mercury Poisoning: Chemical Speciation of Hair Mercury Shows a Peak of Inorganic Mercury Value
Authors: Suzuki T. , Hongo T. , Matsuo N. , Imai H. , Nakazawa M. , Abe T. , Yamamura Y. , Yoshida M. , Aoyama H. 
Published: December 2008

A woman ingested a dose of sublimate (approximately 0.9 g) in an attempted suicide. She survived and recovered in response to a combination of therapies including chelate (BAL) therapy, plasma exchange, haemodialysis and peritoneal dialysis. Serum inorganic mercury concentration, urinary inorganic mercury excretion and hair inorganic and organic mercury and selenium concentrations, along the length from the scalp to the distal part, were measured. Longitudinal analysis of hair, revealed a peak in inorganic mercury corresponding to the time of mercury ingestion. Organic mercury and selenium in the hair had different patterns of longitudinal variation from that of inorganic mercury. The biological half-life (23.5 d) of serum inorganic mercury levels was in good agreement with values previously reported in the literature.
Interindividual Variations in Enzymes Controlling Organophosphate Toxicity in Man
Authors: Mutch Elaine , Blain Peter G. , Williams Faith M. 
Published: December 2008

1 Interindividual variations in an unexposed population have been defined for five enzymes involved in organophosphate (OP) toxicity. The enzymes measured were: red blood cell acetylcholinesterase (AChE), lymphocyte neuropathy target esterase (NTE), serum cholinesterase (ChE), serum paraoxonase and serum arylesterase. 2 AChE and arylesterase were normally distributed in the population whilst the distribution of NTE, ChE and paraoxonase deviated significantly from normal. 3 Assay precision and intra-individual variability were measured for each of the enzymes; the effect on interindividual variation was assessed. 4 Variations in enzyme activities between individuals could have profound effects on susceptibility to OP toxicity. Prior determination of these enzymes may be predictive of susceptibility. 5 Lymphocyte NTE has some limitations as an indicator of exposure to neurotoxic OPs.
Biochemical and Histological Alterations in Rats after Acute Nitrogen Dioxide Intoxication
Authors: Meulenbelt J. , van Bree L. , Dormans J.A.M.A. , Boink A.B.T.J. , Sangster B. 
Published: December 2008

1 In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication. 2 Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. 3 After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) 1 the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. 4 The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, β-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the β-glucuronidase activity showed a 10-fold increase. 5 Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. 6 Repair was almost complete 7 d following exposure.
Long-Term Anticonvulsant Therapy Worsens Outcome in Paracetamol-Induced Fulminant Hepatic Failure
Authors: Bray Gary P. , Harrison Philip M. , O'Grady John G. , Tredger J. Michael , Williams Roger 
Published: December 2008

1 Paracetamol hepatotoxicity has been found to be potentiated by anticonvulsant drugs in animal experiments; isolated case reports in humans sugest that long-term anticonvulsant therapy may also adversely influence outcome following overdose.2 We compared the clinical course, after paracetamol overdose, of 18 patients on long-term anticonvulsant therapy with corresponding features in two published series of paracetamol-induced fulminant hepatic failure from this unit: 297 patients seen between 1973 and 1985 and a further 99 between October 1986 and April 1988.3 Mortality in those patients who were taking anticonvulsants, but who did not receive N-acetylcysteine, was higher than in either of these series (93.3% vs 64.6% and vs 57.9%, P< 0.025). Although not statistically significant, there were also trends towards more severe coma (grade 3 or 4: 93.3% vs 75.4%, 1986-88), acidosis (pH less than 7.30: 40% vs 22.6%, 1973-85) and coagulopathy (prothrombin time greater than 100 s: 53.3% vs 33.7%, 1973-85). In the small number of patients given N-acetylcysteine, mortality was similar to that in the 1986-88 series (1/3 vs 15/42).4 We conclude that chronic use of anticonvulsants enhances clinical features of paracetamol toxicity and discuss possible mechanisms by which this could be mediated.
The Role of Ecotoxicology in the Assessment of Human Exposure to Chemical Substances
Authors: Calamari D. 
Published: December 2008

In the late 1970s new legislation was established in many industrialized countries in order to protect the environment. This has led to the definition of a new branch of science: ecotoxicology. The development of predictive approaches for the hazard assessment of chemical substances has given increased relevance to exposure evaluation. This paper discusses the problems related to the environmental distribution and fate of chemicals and their potential use in the assessment and prediction of exposure of the general population, through air, drinking water and food. Collaboration between toxicologists and ecotoxicologists is urged to improve our capability to manage chemicals.
A Pattern of Acute Poisoning in Children in Urban Zimbabwe: Ten Years Experience
Authors: Kasilo Ossy M.J. , Nhachi Charles' F.B. 
Published: December 2008

1 A retrospective analysis was performed to evaluate the epidemiology of poisoning in children based on admissions to six of Zimbabwe's main urban hospitals over a 10-year period from 1980 to 1989 inclusive. 2 A total of 2873 cases were children aged between 0-15 years. This constituted 47.8% of poisoning cases from all age groups (6018) recorded during the study period. 3 All of the children (0-15 years) had signs and symptoms of poisoning on admission and, depending on their severity, were admitted to a ward or to an intensive care unit. A total of 4.9% (141) died. Most of those who died were suicide cases among the 11-15 year age group and accidental poisonings among the 0-15 year old group. 4 The under 0-5 age group constituted the majority of cases (75.4%) in the 0-15 age group, and most were between 1 and 3 years old. The 6-10 and 11-15 age groups formed 12.6% and 12% of the cases, respectively. The sex distribution showed that 53.1% were male. 5 Most incidences were accidental (93.2%). Suicides and parasuicides accounted for 1.9% and there were only two homicides. 6 The commonest toxic agents were: household products (27.2%), traditional medicines (23.%), venoms from snake bites and insect stings (16%) and therapeutic agents (12.4%). Of the therapeutic agents the most frequently implicated were antipsychotics 18.9%, analgesics 16.8%, anti-infectives 11.7%, anticonvulsants (8.2%) and benzodiazepines (7.7%). 7 The incidence of poisoning could be significantly reduced by health education directed at parents with emphasis on the safe storage of paraffin, drugs and household chemicals. An improvement in living conditions would also offer direct benefits.
Lack of Acipimox-Digoxin Interaction in Patient Volunteers
Authors: Chijioke Chioli Pascal , Pearson Richard Martin , Benedetti Strolin 
Published: December 2008

1 A study was carried out to find out if digoxin and acipimox interact. 2 Six elderly patients on digoxin were each given acipimox 150 mg three daily for a week, after informed consent. Digoxin and acipimox plasma concentrations and urinary excretion were measured after the first dose of acipimox and after a week of treatment. 3 Data were fitted to a one-compartment oral absorption model. Areas under the plasma concentration-time curve, plasma and renal clearances, and elimination half-life were computed. 4 There was no significant difference in digoxin plasma concentrations and kinetic parameters before and after acipimox administration. Acipimox kinetics were not affected by the concomitant ingestion of digoxin. 5 The patients' clinical condition remained stable during the study. 6 Thus there was no evidence for an adverse interaction between digoxin and acipimox in human subjects under the conditions of this study.
Clinical Course, Therapy, Outcome and Analytical Data in Amitriptyline and Combined Amitriptyline/Chlordiazepoxide Overdose
Authors: Köppel C. , Wiegreffe A. , Tenczer J. 
Published: December 2008

A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2), treated at our Intensive Care Unit or reported to our Poison Information Center between 1985-1990, were evaluated with respect to clinical course, symptoms and outcome, as well as efficacy of therapy. The mean amount of AT was considerably higher in group 1 compared to group 2 (13 mg kg-1vs 7.7 mg kg-1). The most frequent symptoms in both groups were impaired consciousness, anticholinergic symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency necessitated respirator therapy in 63 of the patients. Two patients in group 1 and one patient in group 2 did not survive.Therapy included primary detoxification by gastric lavage and repeated administration of activated charcoal. In four of eight patients with cardiac conduction disturbances, hypertonic sodium bicarbonate led to a significant reduction in QRS duration and AV interval. Physostigmine was effective in eight of 14 patients with pronounced anticholinergic symptoms. No effect was observed in the other six patients. Haemoperfusion, which was performed in five patients, led to rapid improvement of coma after initiation of therapy in four patients. The clinical efficacy of haemoperfusion in AT overdose despite the high volume of distribution of AT deserves further investigation.The rather high average overdose of AT implies that large package sizes of AT were available to the patients. A major step towards prevention of serious AT overdose would be the prescription of package sizes containing a total amount of less than 500 mg AT.Different analytical methods (enzyme immunoassay, fluorescence polarization immunoassay, and gas chromatography/mass spectrometry) for rapid detection of AT and its metabolites in plasma and urine were evaluated. Commercially available immunoassays like EMIT and ADX were highly reliable and sensitive in the detection of AT overdose. Five previously unknown metabolites or derivatives of AT could be detected in cases of AT overdose with the aid of a gas chromatography/mass spectrometry screening procedure.
Long-Term Study of Brain Lesions Following Soman, in Comparison to DFP and Metrazol Poisoning
Authors: Kadar T. , Cohen G. , Sahar R. , Alkalai D. , Shapira S. 
Published: December 2008

The long-term histopathological effects of acute lethal (95 μg kg-1) and sublethal (56 μg kg-1) doses of soman were studied in rats and were compared to lesions caused by equipotent doses of either another cholinesterase (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant, metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose administration of all the compounds, yet only soman induced brain lesions. Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced some histological changes without any clinical signs of intoxication. Soman-induced brain lesions were assessed quantitatively using a computerized image analyser. The analysis was carried out for up to 3 months following administration, and a dynamic pattern of pathology was shown. The cortical thickness and area of CA1 and CA3 cells declined significantly as early as 1 week post-exposure. No pathological findings were detected following DFP and metrazol administration. It is therefore suggested that brain lesions are not common for all ChE inhibitors and that convulsions per se are not the only factor leading to brain damage following the administration of soman. The degenerative process (found also with the sublethal dose of soman) might be due to a secondary effect, unrelated to soman's clinical toxicity, but leading to long-term brain injuries.