我国环境流行病学研究中的神经行为功能评价方法

许多环境有害因素具有神经毒性,将神经行为学评价方法应用于环境流行病学,不仅有利于判断环境有害因素对机体的早期、潜隐性损害,而且可以及早筛检出受累人群,防止其发展为不可逆性损伤.目前,国内外神经行为学评价方法种类繁多,该文对国内适用于环境流行病学研究的几种神经行为学评价方法及其应用进行了综述.     

茶多酚毒理学实验研究

目的:观察动物对茶多酚的急性和慢性的毒性反应。方法:将小白鼠分为5组,其剂量分别为4.5、3.57、2.84、2.26和1.8g/kg,剂量间距为1∶0.8,一次性灌胃(ig)给药,观察7 d,按改良寇氏法计算LD50。大白鼠分为3组,高低剂量分别ig给予833、83.3 m g/kg的茶多酚,阴性对照组ig给同容量的生理盐水,连续灌胃6个月,观察长期毒性反应。结果:小白鼠ig茶多酚LD50为(2.64±0.254)g/kg。大白鼠长期灌服茶多酚后,体重增长、血常规、血液生化及脏器系数各项指标均在正常范围内,病理组织学检查未见异常。结论:茶多酚急性毒性低。大白鼠长期灌服茶多酚(833 m g/kg.-d 1),相当于人拟用日剂量的100倍也是安全的。     

马钱子的毒理学实验研究

为了解自制颈椎敷贴药用药的安全性 ,对其君药及主要毒性药物马钱子 (SemenStrychni)粉 ,进行了口服急性毒性试验、皮肤急性毒性试验和皮肤刺激试验。结果昆明小鼠口服给药LD50 =2 5 0 .8mg·kg-1,豚鼠皮肤急性毒性试验未发现毒性作用 ,豚鼠皮肤刺激试验显示高剂量组 (6 7% )对擦伤皮肤具有一定刺激性。表明该药外用于完整皮肤 ,具有良好的安全性     

Cardiotoxic Effect of Primaquine in Mammals:Histological and Ultrastructural Investigation

It has been known that the antimalarial drugs of aminoquinolinesincluding 8-aminoquinolines may cause inhibition of heart conduction or evenAdams-Stokes syndrome,but their morphologic bases were obscure.The purposeof the present study is to define the histological and ultrastructural features ofprimaquine in mammals including dogs,monkeys and rats in the subacute toxicexperiments with the stress on the morphological alteration of the heart.In most(11/16)of the intoxicated dogs,granular degeneration,eosinophilic degeneration,coagulation necrosis,vacuolar degeneration and colliquative myocytolysis werefound in the myocardium and conduction systems.Under electron microscopicstudy,the myocardial cells of intoxicated dogs showed swelling of mitochondria,dilatation of transverse tubules and sarcoplasmic reticulum,fusion or dissolutionof myofibrils,deformity of nuclei,clumping of chromatin,and eventually cellnecrosis.The severities of lesions were dose dependent.These lesions weresupposed to be the morphologic evidence of the toxic symptoms and signs caused byprimaquine.A few rats also revealed myocardial eosinophilic degeneration.Noimportant cardiac lesions were found in the monkeys,but the pathologic changesin the liver were obvious.Different species of laboratory animals showed differentorgan sensitivities to primaquine,but the heart lesions should be considered as animportant toxic effect of primaquine.     

Short term effects and urinary excretion of the new diuretic,indapamide, in normal subjects

Summary The pharmacology, toxicology and kinetics of a new diuretic indapamide, have been studied in six normal volunteers following a single oral dose of 40 mg. Pronounced diuresis was found, commencing three hours after ingestion, with a peak urinary flow at four to six hours, and continuing for a total of thirty-six hours. A fall in systolic standing blood pressure occurred twenty four hours after ingestion, coincident with the period of maximum dehydration. Free water clearance rose, accompanied by increased urinary losses of Na⁺, K⁺ and Cl^– and alkalinisation of the urine comparable to the actions of benzothiadiazines. Total urinary losses of Ca²⁺, Mg²⁺ and PO ₄ ^3– rose in spite of a fall in urinary concentrations of these ions. The Ca²⁺ effect compares with the acute ionic effects of other diuretics. No renal, hepatic or haematological toxic effect was demonstrated. The blood sugar level was not disturbed. Serum uric acid rose to abnormal levels although the change did not reach statistical significance. — A thin layer chromatographic method, with a sensitivity limit of 0.1 µg/ml., has been developed for the assay of indapamide in urine. The urinary excretion rates of the volunteers measured over forty-eight hours indicate that the drug is rapidly absorbed with a peak excretion, 2.9±1.3 µg/min occurring three hours after ingestion. The drug is eliminated bi-phasically with an initial short rapid elimination followed by a slower exponential decline with a mean elimination half-life of 10.3 ± 3.9 h. The mean urinary excretion of unchanged indapamide over forty-eight hours was 4.4±1.4% of the administered dose. — It is concluded that indapamide is an effective long-acting diuretic with comparable action to the benzothiadiazine diuretics, but without an effect on blood sugar level in single doses in normal subjects. In contrast with other diuretics, indapamide appears to be extensively metabolised in man, and its longer duration of action to be related to a longer elimination half-life.     

Modulation of the genotoxicity of pesticides reacted with redox-modified smectite clay

Pesticides are toxic agents intentionally released into the environment; their use raises public health and environmental concerns. In recent years there has been much attention to the biotic degradation of pesticides. Abiotic mechanisms in the soil can contribute to pesticide degradation yet the toxicological impact of such degradation is unclear. This study combines for the first time an investigation into abiotic mechanisms of degradation coupled with toxicological endpoints in mammalian cells. The genotoxicity of three commonly used agricultural pesticides was assessed before and after exposure to redox-modified clay minerals. The objectives of the study were to determine the genotoxicity of 2,4-dichlorophenoxy acetic acid (2,4-D), dicamba, and oxamyl, using single cell gel electrophoresis with Chinese hamster ovary (CHO) cells, and to determine the effect of the iron oxidation state in clay minerals (ferruginous smectite SWa-1) on the genotoxic potency of the pesticides. 2,4-D alone or following reaction with redox-modified clays did not induce DNA damage in CHO cells. Oxamyl alone induced a concentration-dependent increase in genomic DNA damage; however, its genotoxicity declined after reaction with reduced clay minerals. Dicamba was not genotoxic when directly analyzed. When dicamba was reacted with reduced clay, a concentration-dependent increase in genomic DNA damage was observed. This is the first reported case of a pesticide being converted into a genotoxin after exposure to redox-modified smectites. These data introduce a new paradigm on the interaction between redox-modified clays and pesticide-related environmental genotoxicity.     

Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides

OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. METHOD: Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26,422 cases of deaths by accident or natural causes in Sweden 1992-2000. RESULTS: There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION: The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.     

The toxicology of Amanita virosa: the destroying angel

This paper examines the biology and medical consequences of ingesting the potentially lethal poisonous mushroom, Amanita virosa, the Destroying Angel. The fungus, its structure, distribution and toxic components are described. Symptoms of human poisoning by A. virosa are described, following the order of Homeopathic Repertories. Laboratory values for comparison with normal values of haematology, biochemistry and urine analyses are given.     

Reproductive evaluation of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar rats

The present study was conducted to evaluate the toxicity of the exposure to the aqueous extract from leaves (AE) of Achillea millefolium L. on reproductive endpoints in Wistar rats. Adult male rats were treated daily with yarrow extract (0.3, 0.6 and 1.2 g/kg/day) during 90 days by oral gavage. Endpoints including reproductive organ weights, sperm and spermatid numbers as well as sperm morphology were evaluated. No clinical signs of toxicity were detected over the treatment period, and body weight gain was similar in all groups. A significant increase in the percentage of abnormal sperm in the group treated with the highest dose of yarrow extract was detected with no other important changes in the other reproductive endpoints studied in the male rats. Furthermore, a possible estrogenic/antiestrogenic activity of the yarrow extract screened after a 3-day treatment of immature female rats which did not show any uterotrophic effects.     

Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent,for vaginal prophylaxis

OBJECTIVE: To assess the contraceptive properties, antimicrobial activity, and safety of mandelic acid condensation polymer (SAMMA). DESIGN: Experimental study of SAMMA's in vitro and in vivo properties. SETTING: Academic research laboratories. PATIENT(S): Healthy volunteers for semen donation in an academic research environment. INTERVENTION(S): Inhibition of sperm function indicators, conception, sexually transmitted infection-causing pathogens (including HIV), and lactobacilli was evaluated. Safety indicators were studied. MAIN OUTCOME MEASURE(S): Quantitation of SAMMA's effect on microbial infectivity or multiplication and on sperm function in vitro; evaluation of contraceptive efficacy in vivo; assessment of safety in vitro and in vivo. RESULT(S): Mandelic acid condensation polymer is not cytotoxic toward lactobacilli, microbial host cells, and spermatozoa. The compound inhibits hyaluronidase and acrosin, induces sperm acrosomal loss, and is contraceptive in the rabbit model. Mandelic acid condensation polymer prevents infectivity of HIV and herpesviruses 1 and 2 and, to a lesser extent, of Chlamydia trachomatis. It inhibits the multiplication of Neisseria gonorrhoeae. Mandelic acid condensation polymer is not mutagenic, has low acute oral toxicity, and is safe in the rabbit vaginal irritation assay. CONCLUSION(S): Mandelic acid condensation polymer inhibits sperm function, is contraceptive, has broad-spectrum antimicrobial activity, and is highly safe. Further development as a microbicide is warranted.