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101.
G. Seghieri G. C. Bartolomei L. A. De Giorgio F. Innocenti A. Gironi M. Mian F. Franconi 《European journal of clinical pharmacology》1989,37(4):401-404
Summary Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age >60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD.The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI > the median value, were characterized by a lower daily dose and dosage frequency.Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug. 相似文献
102.
CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine 总被引:2,自引:2,他引:0
We have investigated several factors that might be related to the occurrence of toxic effects during the performance of a urinary test with caffeine (300 mg p.o), in 120 healthy volunteers. A total of 218 toxic effects were self-reported by eighty-two (68%) subjects. Females and nonsmokers were at the highest risk (chi-square test, P =0.01). Furthermore, two nonsmoking females experienced a symptomatology with delirium, restlessness, muscle tremor, vomiting and wakefulness. Among females and nonsmokers, those subjects who experienced toxic effects had lower caffeine N3-demethylation index (CYP1A2 activity) compared with unaffected females (1.87±0.51 vs 1.47±0.27, P <0.0005) and nonsmokers (1.69±0.23 vs 1.49±0.31, P <0.02). Caffeine N1- and N7-demethylations indices were also lower among females ( P <0.0005) and nonsmokers ( P <0.02) who reported toxic symptoms. We conclude that CYP1A2 activity, gender and smoking are variables to be considered as influencing the toxicity of caffeine. 相似文献
103.
E. V. Grishina V. P. Shchipkov A. P. Pekhov 《Bulletin of experimental biology and medicine》1995,120(6):1233-1235
The inhibition of conjugative transfer of derepressed plasmids was appreciably increased in polyplasmid complexes ofEscherichia coli K-12 cells containing two repressed conjugative plasmids with the finV system of genetic transfer regulation, in comparison
with the individual effects of each of the two plasmids. Combination of two plasmids with the finU system or of plasmids with
the finU and finV systems did not result in such an increase of inhibitory activity.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N
o
12, pp. 619–622, December, 1995
Presented by T. T. Berezov, Member of the Russian Academy of Medical Sciences 相似文献
104.
通过对金锁匙口服液的药效学及毒性的研究表明:本品能明显抑制吗啡依赖性小白鼠停药后的跳跃反应,协同戊巴比妥钠催眠作用,提高小鼠热板法痛阈值,抑制醋酸引起的小鼠扭体反应,提示金锁匙口服液对吗啡类成瘾患者有一定的治疗作用,毒理研究表明;本品服用无药物依赖性、安全、无毒。 相似文献
105.
Recent studies have shown that tetrafluoroethylene is a renal and hepatic carcinogen in the rat. In this study, we have examined
the ability of a single i.p. dose of 1,1,2,2-tetrafluoroethyl-l-cysteine (TFEC), a major metabolite of tetrafluoroethylene, to produce hepatic and renal injury in male and female rats.
We have also examined the effect of blocking the renal organic anion transport system with probenecid and of inhibiting the
activity of cysteine conjugate β-lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC. Doses of ≥12.5 mg/kg
TFEC produced renal tubular necrosis to the pars recta of the proximal tubules within 24 h in both male and female rats. This
was associated with an increased kidney to body weight ratio and plasma urea at doses of ≥25 mg/kg. No consistent evidence
of liver injury was seen at doses up to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of hepatocytes
and a small dose-related increase in liver to body weight ratio was observed. Prior treatment of female rats with probenecid
completely prevented the renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and histopathology.
However, prior treatment of female rats with aminooxyacetic acid afforded no protection against the nephrotoxicity produced
by either TFEC or the cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in nephrotoxicity in the
rat was seen with TFEC, while accumulation of TFEC, or its N-acetyl derived metabolite, into renal proximal tubular cells
via a probenecid sensitive transport system appears to be a key event in the mechanism of nephrotoxicity. The lack of protection
observed with the cysteine conjugate β-lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely inhibit
the mitochondrial form of this enzyme and thereby prevent the formation of the reactive metabolite. Our acute studies provide
no insight concerning the liver carcinogenicity of tetrafluoroethylene.
Received: 8 December 1997 / Accepted: 3 February 1998 相似文献
106.
The influence of a fraction obtained from Galeopsis ladanum L. on the central nervous system of rodents was examined. The results of these investigations show that the fraction impeded CNS activity. It is practically nontoxic and at a dose of 2000 mg/kg i.p. it does not have a soporific influence on mice. It reduces considerably the spontaneous locomotor activity of mice as well as the locomotor activity of mice stimulated by caffeine, but did not influence the locomotor activity induced by amphetamine. The extract did not exhibit a synergetic effect with barbiturates. The results suggest that the pharmacological activity of the extract resembled the activity of drugs which generally depress the CNS, being on the border between ataractic and sedative drugs. 相似文献
107.
Dermal toxicity of Fusarium toxins in combinations 总被引:3,自引:0,他引:3
T 2 toxin (T 2), diacetoxyscirpenol (DAS), fusarenon X (FX) and butenolide (Bd) at concentrations of 0.2, 0.3, 5 and 10 g/site, respectively, were applied individually and in combinations on shaved skin of guinea pigs. Erythema and induration were observed on skin patches treated with the toxins. Increase in the thickness of stratum malpighii was the major histological change observed. Mild to moderate degeneration of fibrocytes and cellular infiltration were found in the corium of skin treated with FX, Bd, DAS and T 2. The order of toxicity of individual toxins was T 2 > DAS > FX > Bd. Combinations of T 2 + FX and T 2 + Bd resulted in antagonism, while DAS + FX and DAS + Bd caused synergism. 相似文献
108.
Gerald C. Clark 《Archives of toxicology》1988,62(5):381-386
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. 相似文献
109.
背景 育龄期女性胚胎着床失败及流产的最常见原因是胚胎异常,但移植经胚胎种植前遗传学检测(PGT)筛选后的正常胚胎后,仍出现种植失败或流产的原因目前并没有形成统一的结论。目的 分析PGT助孕后种植失败及流产的影响因素。方法 回顾性分析2018年12月至2021年2月在安徽医科大学第一附属医院生殖中心行PGT助孕的329例患者的临床资料,根据患者是否临床妊娠分为临床妊娠组(n=218)和种植失败组(n=111),并将临床妊娠组患者根据妊娠结局分为活产亚组(n=175)和流产亚组(n=43)。比较临床妊娠组和种植失败组,活产亚组和流产亚组的一般情况、促排卵及体外胚胎发育情况。采用多因素Logistic回归分析探讨PGT患者种植失败及流产的影响因素。绘制受试者工作特征(ROC)曲线分析多因素Logistic回归分析筛选出的影响因素对PGT患者发生种植失败及流产的预测价值。结果 多因素Logistic回归分析显示,既往流产次数≥2次〔OR=4.032 0,95%CI(2.423 0,6.710 0)〕、高密度脂蛋白胆固醇(HDL-C)水平低〔OR=3.890 0,95%CI(1.455 0,10... 相似文献
110.
[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。 相似文献