Human toxicology最新文献

A study is presented in which eight healthy male non-smoking volunteers ingested a daily amount of 0.5 mg/kg butylated hydroxyanisole (BHA) for 10 consecutive days. Blood samples were taken on days -6 and 0 before and on days 4 and 7 after the first BHA administration for the assessment of standard clinical plasma parameters (L-aspartate aminotransferase, L-alanine-aminotransferase, L-gamma-glutamyltranspeptidase, creatine phosphokinase, lactate dehydrogenase, total protein, albumin, urea, creatinine, Na+, and Cl-). Antipyrine (500 mg p.o.) and paracetamol (500 mg p.o) were administered before and during BHA administration as test substances to measure phase-I and phase-II biotransformation capacity. Saliva samples and urine were subsequently collected for the assessment of kinetic parameters (e.g. saliva elimination half-life, saliva clearance, apparent volume of distribution) and urinary excretion of metabolites. Kinetic plasma parameters of BHA itself were determined in plasma samples obtained via a catheter in an arm vein after oral BHA intake on days 0 and 7. Levels of antipyrine, paracetamol, BHA and metabolites in plasma, saliva or urine were quantified by standard or newly developed reversed-phase high-performance liquid chromatography methods. Urinary excretion of Na+, K+, and Cl-, as well as osmolality of urine were measured on three days before and six days during BHA administration. Generally, no significant differences were detected in the parameters measured, indicating that oral administration of BHA to men for 10 days remains without effects on clinical biochemical parameters and phase-I and phase-II biotransformation capacity. In contrast, urinary excretion of metabolites of BHA was significantly increased on days 3 and 7 vs. the first day of BHA administration.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Neutrophils play a role in the pathogenesis of ulcerative colitis. Most of the patients with ulcerative colitis are non-smokers. 2. Neutrophil function was examined in healthy males, five smokers and five non-smokers, measuring production of oxygen free radicals by chemiluminescence. 3. The chemiluminescence was examined in the presence of nicotine and its main metabolite cotinine in various concentrations. 4. 10 mM nicotine inhibited production of oxygen free radicals (90.2% +/- 11.6) compared with controls (P less than 0.001), as did the same concentration of cotinine (58.9% +/- 34.2), (P less than 0.05). 5. 1 mM solutions had no effect and 3 mM nicotine was required to achieve 50% inhibition. 6. Smokers and non-smokers did not differ. 7. Since plasma concentrations of nicotine after a cigarette are only between 5 and 15 mM, the observed effects of nicotine and cotinine in much higher pharmacological concentrations in this system are unlikely to be of clinical relevance in ulcerative colitis.

A 50-year-old man with ischaemic heart disease took 98 tablets of diltiazem 60 mg with alcohol. He developed a junctional bradycardia, hypotension and reduced cardiac function refractory to intravenous calcium gluconate. He survived with temporary cardiac pacing and infusion of dopamine. As much as half the dose was vomited back, but nonetheless the plasma diltiazem concentration reached 6090 micrograms/l before falling mono-exponentially with a half-life of 8.6 h. Sinus rhythm returned when the plasma concentration of diltiazem was around 750 micrograms/l. Standard resuscitative procedures sufficed to treat massive diltiazem overdosage.

Sri Lanka is a developing agricultural country with a high fatality rate due to self-poisoning with very toxic agrochemicals as the main poisoning agents. A prospective study of 97 consecutive admissions following self-poisoning reveals that easy availability of the agrochemicals together with the lack of knowledge regarding their lethality were the main causative factors determining the choice of poisoning agents. Developing community awareness of the lethality of these substances, educating the farmers with regards to proper storage and disposal of agrochemicals together with stricter legislation regarding their sale and distribution may reduce the incidence of self-poisoning due to these agents with a consequent reduction in mortality due to self-poisoning.

Two cases who developed haematemesis, 30 and 36 hours after ingestion of 4 tablets (600 mg base) of chloroquine phosphate are described. Upper gastrointestinal endoscopy revealed erosions in the stomach and duodenum.

A 32-year-old female ingested an unknown quantity of Nylax tablets containing phenolphthalein. This results in widespread organ involvement, predominantly causing liver damage and disseminated intravascular coagulation. The eventual cause of death was massive liver necrosis. We suggest that phenolphthalein was responsible for the widespread damage.

Approaches to the assessment of the toxic effects which may arise from chemical Major Hazards are examined. The definitions of hazard and risk and the types of toxicity data required for risk analysis are investigated with particular reference to the quality of the data and models available.

1. The metabolic 4-hydroxylation of debrisoquine has been studied in a group of 98 black African villagers in Vendaland. 2. The metabolic alpha-hydroxylation of metoprolol has been studied in 94 of the same black African villagers. 3. A 4% prevalence of poor oxidative metabolism of debrisoquine and a 7.4% incidence of poor oxidation of metoprolol were found. The 4% result for debrisoquine differs considerably from the 19% found in San Bushmen, 30% in Hong Kong Chinese, 9% in Britains and 0% in Nigerians and Japanese, whilst the 7.4% result for metoprolol compares with 8.4% in Britains but differs from 0% in Nigerians and 4.1% in San Bushmen. 4. None of the poor oxidative metabolizers of debrisoquine were also poor oxidative metabolizers of metoprolol. This is contrary to results in British and Nigerian subjects where defective oxidation of metoprolol co-segrates with that of debrisoquine. 5. No similarities were found between the Venda metabolic ratio (MR) distributions and either extensive or poor MR distributions in Britains or Nigerians.

In a retrospective study over 7 years, data from patients admitted to the Emergency Department with CO intoxication, together with meteorological data were analysed. A statistically significant difference in weather conditions was noticed between CO-intoxication days and reference days. Different weather conditions were found to be present, according to the source of CO, i.e. gas boiler or coal stove. If these data are confirmed, a major role in the prevention of CO intoxication or its sequellae can be played by the media through weather broadcasting. Warning can raise the index of suspicion of physicians and warn the population for vague, collectively appearing sensations of ill feeling.

Methylene blue, at high concentrations, interferes with the estimation of methaemoglobin using the IL 282 CO-oximeter: the dye does not interfere with the method of Evelyn & Malloy for determination of methaemoglobin. In beagle bitches methylene blue causes both methaemoglobinogenesis and methaemoglobin reduction, the effect of the former being to delay the decline of methaemoglobin levels, when methylene blue is used to reverse the methaemoglobinaemia produced by sodium nitrite.