Acute inhalation toxicity of eugenol in rats

The acute toxicity of inhaled eugenol was assessed by exposure of three groups of five male and five female rats to a submicron aerosol of eugenol for 4 h followed by a 14-day observation period. A fourth group, also of five male and five female rats and exposed to air only under similar conditions, served as a control group for comparison. The three concentrations of eugenol to which the different groups were exposed were 2.58, 1.37 and 0.77 mg/l. The mass median aerodynamic diameters and geometric standard deviations of the aerosols were, respectively, 0.82 m (g 2.26), 0.88 m (g 2.05) and 0.9 m (g 1.87). Clinical signs observed during exposure consisted principally of moderately increased salivation and restlessness (indicative of irritation) and abnormal breathing patterns. The signs were graded, being less marked in animals exposed to the lower concentrations of eugenol. All three groups, exposed to high, medium and low levels of eugenol, lost weight overnight following exposure. Associated with the weight loss were marked reductions in food and water intake. The responses appeared to be largely independent of the concentration of eugenol inhaled, although there was some evidence of a graded effect on water intake. There was rapid recovery, with food and water consumption data comparable with control values throughout most of the remainder of the 14-day observation period. Also, by the end of the observation period, group mean body weights were comparable. Upon sacrifice and macroscopic examination of the animals, abnormalities were detected in the lungs only of a few animals: 3/10 control, 2/10 eugenol 2.58 mg/l, and 2/10 eugenol 0.77 mg/l. These consisted of dark red/red (raised) areas up to 4×4 mm. Such abnormalities are not uncommon in the lungs of laboratory maintained rats and their presence with equal incidence in control animals suggests that they are unlikely to be related to inhalation of eugenol. Lung weight to body weight ratio values for all groups were similar, providing no evidence of any persistent effect of eugenol on the lungs of the rats. Similarly, histopathological examination of the lung failed to reveal any treatment-related changes. A few incidental lesions present were considered spontaneous in origin and therefore of no toxicological importance.     

甘草地上部分活性部位的急性毒性和长期毒性实验研究

[目的] 探索甘草地上部分活性部位对小鼠的急性毒性及大鼠的长期毒性,评价其安全性,为合理开发利用甘草地上部分资源以及临床应用提供可靠的理论依据。[方法] 甘草地上部分活性部位33.2 g/kg灌胃给予昆明种小鼠,24 h内两次（间隔5 h）经口灌胃给予受试物,持续观察14 d内小鼠的急性毒性反应;SD大鼠随机分为对照组和甘草地上部分低、中、高剂量组,按8.3、16.6、33.2 g/kg剂量连续灌胃甘草地上部分活性部位90 d,观察大鼠的一般状况,并分别于给药后45、90 d进行血液学指标检测与血清生化指标检测,给药后90 d进行大体解剖及病理学检查,观察甘草地上部分活性部位的长期毒性反应。[结果] 急性毒性实验中小鼠的一般状态、饮食、分泌物、排便未见异常,无小鼠死亡,肉眼尸检心、肝、脾等主要脏器组织未见明显异常;长期毒性实验中,各组大鼠与对照组比较,一般状况、血液学及血清生化指标未见明显差异;病理检查未见主要脏器组织形态学改变。[结论] 甘草地上部分活性部位无急性毒性和长期毒性,在治疗剂量范围内用药安全性高。     

The effect of hyperoxia on the lungs of rats deficient in essential fatty acids

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.(Murakami R, Obara H, Momota T et al.: The effect of hyperoxia on the lungs of rats deficient in essential fatty acids. J Anesth 3: 149–154, 1989)     

五味与毒性关系的探讨

毒性的产生应有物质基础,这种物质基础就是五味,中药的功效和毒性均来自五味。在五味中有毒药物的数量以辛、苦味为多,甘味最少,酸、咸味居中。     

Antibodies to squalene in recipients of anthrax vaccine

We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel. Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA. In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05). Further analysis revealed that ASA were associated with specific lots of vaccine. The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine. Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene. Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene. ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel. Three of these individuals became ASA positive after vaccination. These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine.     

Conventional anticonvulsant drugs in the guinea pig kindling model of partial seizures: effects of acute phenobarbital,valproate, and ethosuximide

This study addressed the anticonvulsant effects of phenobarbital, valproate, and ethosuximide in the amygdala of kindled guinea pigs to further validate this model for the screening of anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using quantitative locomotor tests, as well as scores on a sedation and muscle relaxation rating index. The anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioral seizure severity (SS) during early and late phases of kindling acquisition, and in kindled guinea pigs. ADD and SS were also measured in response to both threshold and suprathreshold kindling stimulation. All drugs exerted slight to moderate sedative effects in guinea pigs on both the behavioral tests and rating index. We found that phenobarbital exhibited effective anticonvulsant properties in guinea pigs by consistently reducing ADD and SS in response to both threshold and suprathreshold kindling stimulation. Valproate exhibited effective anticonvulsant properties at threshold stimulation and less effective properties at suprathreshold stimulation. Lastly, we found that ethosuximide lacked effective anticonvulsant action at either threshold or suprathreshold kindling stimulation. Our results indicate that the guinea pig kindling model correctly predicted the actions of phenobarbital, valproate, and ethosuximide in the treatment of partial seizures. Guinea pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.     

Hematological reference intervals in argentine lizard <Emphasis Type="Italic">Tupinambis merianae</Emphasis> (Sauria—Teiidae)

In order to establish referential hematological parameters, blood samples were taken from 100 healthy specimens of the Argentine tegu lizard (Tupinambis merianae) by means of venipuncture of ventral coccigeal vein. The determination of red blood cells, leukocyte and thrombocyte count, hematocrit, hemoglobin concentration, hematometric index and differential leukocyte count were performed, and compared with other saurian species. No statistically significant changes were observed as function as sex and age (p > 0.01). During winter, high values of red blood cell counts, hematocrit and hemoglobin were observed (p < 0.01), while in summer significantly increased leukocyte and thrombocyte counts were observed (p < 0.01). The differential leukocyte counts were not affected by the studied factors.     

Missed diagnosis in hematological patients—an autopsy study

Autopsy findings of missed diagnoses that would probably have changed management or prognosis occur in up to 29% of cases in general hospitals. Such proportions may be higher in subsets of patients with complex diseases. We reviewed 2908 consecutive autopsies performed over a period of 29 months in a large-volume hospital, analyzing 118 autopsies of patients with hematological malignancies or severe aplastic anemia. A review of macroscopic reports as well as microscopic examination of tissue samples was performed. Medical records were reviewed for clinical diagnoses. Discordances between clinical and autopsy diagnoses were classified using Goldmans criteria. Additionally, we searched for clinical parameters correlated with occurrence of class-I discrepancy using a multivariate method. Median age was 46.5 years, and 25.4% had received a hematopoietic stem-cell transplant. Overall, 11.9% (6.6–19.1%) of patients died before conclusion of the hematological diagnosis and 33% (24.6–42.3%) died with no active hematological disease. We found class-I discrepancy in 31.3% (23.1–40.5 %) of cases. The most common among these diagnoses were hematological disease, pneumonia and gastrointestinal bleeding. In a univariate analysis, being elderly (P=0.04) was positively correlated with the finding of class-I discrepancies; while, having received previous specific hematological treatment (P=0.0005) or hematopoietic stem-cell transplants (P=0.013), or being admitted to a specialized hematology unit (P=0.0006) were negatively correlated to the occurrence of such discrepancies. Multivariate analysis showed that care in a specialized hematology unit (OR 0.34, 0.12–0.93) was independently associated with lower occurrence of discrepancies. We concluded that critical diagnoses are often missed in highly complex hematological patients especially in the absence of admission to specialized hematology units.     

Bronchopulmonary Dysplasia: A Correlative Study by Light, Scanning, and Transmission Electron Microscopy

The sequential stages of bronchopulmonary dysplasia occurring in 18 infants after intensive respiratory therapy supplemented by oxygen in high concentrations were studied by correlative light, scanning, and transmission electron microscopy. Infant survival ranged from 3 to 225 days. The earliest stage was an exudative reaction with a predominance of hyaline membranes. This merged with a subacute reparative response that was replaced by a chronic fibroproliferative stage in infants of longest survival; this stage was complicated by pulmonary fibrosis and emphysema. Correlative scanning and transmission electron microscopy demonstrated that type 2 pneumocytes contributed significantly to the reparative fibroproliferative response by organization of hyaline membranes and reepithelialization of damaged septal walls.     

顺铂和替加氟联合放疗治疗中晚期食管癌疗效观察

目的观察顺铂和替加氟联合放疗治疗食管癌的临床疗效及其毒副反应。方法2003年1月至2006年2月对60例食管癌患者采取顺铂20mg·m-2·d,替加氟750mg·m-2·d,连用5天,序贯放疗60~70Gy/6~7周。结果60例患者中,CR24例,PR18例,SD9例,PD9例,RR(CR+PR)为70·0%,主要毒副作用为骨髓抑制、恶心呕吐。肝肾功损害及口腔炎、静脉炎等较轻。结论顺铂和替加氟联合放疗治疗食管癌疗效好,耐受性好值得推广应用。