尼美舒利对照阿司匹林或复方氨基比林治疗儿童发热的Meta分析

目的 评介尼美舒利对比阿司匹林、复方氨基比林在儿童发热治疗中的疗效和安全性.方法 计算机检索Pubmed、Cochrane图书馆、CBM、CNKI、维普数据库,检索时间至2011年2月,纳入符合标准的随机对照试验,依据Cochrane系统评价方法评价文献质量,数据采用Revman5.0.0.进行Meta分析.结果 纳入13个RCT共计1200例患者,Meta分析结果显示尼美舒利对照阿司匹林,服药1h体温(MD=0.38,95%CI[0.212,0.55],P<0.0001)和6 h体温(MD=1.01,95%CI(0.53,1.49],P<0.0001)差异有统计学意义.结论 本次研究显示,尼美舒利降温效果优于阿司匹林和复方氨基比林,但较易导致嗜睡,其他不良反应尚有待进一步研究.     

Effects of the interferon inducing agents tilorone and polyriboinosinic acid · polyribocytidylic acid (poly IC) on the hepatic monooxygenase systems of pregnant and fetal rats

Interferon inducing agents, including tilorone and polyriboinosinic acid polyribocytidylic acid (poiy IC), are known to depress hepatic cytochrome P-450-dependent monooxygenase systems and the induction of these systems by phenobarbital (PB) and 3-methylcholanthrene (MC) in mature male rats. The current study investigated the effects of tilorone and poly IC on the cytochrome P-450 systems of non-induced, PB-induced, MC-induced and pregnenolonecarbonitrile (PCN)-induced pregnant rats and their fetuses. Pregnant rats received either tilorone or poly IC and saline, PB, MC or PCN, and microsomes from their livers and those of their fetuses were examiued for cytochrome P-450 content, aminopyrine (AP) N-demethylase activity and benxo[a]pyrene (BP) hydroxylase activity. The generalixation can be made from these studies that, when the interferon inducing agents caused changes in cytochrome P-450 content or monooxygenase activities of either induced (PB, MC or PCN) or non-induced (saline) animals, decreases were seen in maternal livers and increases in fetal livers. Thus, in maternal livers tilorone depressed cytochrome P-450 and AP N-demethylase activity in non-induced and PB-, MC- and PCN-induced rats and BP hydroxylase activity in the induced animals; BP hydroxylase activity was not depressed in non-induced maternal livers. Poly IC depressed cytochrome P-450 and AP N-demethylase activity in non-induced and PB-induced rats but not in PCN-induced animals. BP hydroxylase was depressed by poly IC in both PB- and PCN-induced animals. Fetal hepatic cytochrome P-450 and monooxygenase activities were increased by tilorone in PB- and PCN-induced rats but not in non-induced or MC-induced animals. Poly IC increased cytochrome P-450 and both monooxygenase activities in PB- and PCN-induced fetal livers, whereas only BP hydroxylase activity was increased in the fetuses of non-induced rats. Several possible explanations are offered for the opposite effects produced by interferon inducing agents in maternal and fetal livers. Unlike maternally administered tilorone, which induced fetal cytocbrome P-450 and monooxygenase activities in the liver, intrauterine tilorone depressed cytochrome P-450 and had no effect on AP N-demethylase or BP hydroxylase activities in the fetal liver. Intrauterine poly IC was without effect on the cytochrome P-450 systems of the fetal liver. Treatment of pregnant rats with tilorone on days 17–20 of gestation inhibited normal maternal weight gain and produced overt signs of toxicity. A dose of 10 mg/kg of poly IC was very toxic in pregnant rats but produced no overt signs of toxicity in virgin female rats. Time courses of the depressant effects of a single injection of poly IC were observed in mid-term pregnant, late-term pregnant, lactating and adult virgin females. Maximum losses of cytochrome P-450 and ethyhnorphine (EM) N-demethylase activity were seen 48 hr after poly IC administration to pregnant and virgin rats, and recoveries were complete within 96 hr. Similar results were observed in lactating rats except that the nadir occurred at 24 rather than at 48 hr. The response of BP hydroxylase activity to poly IC was qualitatively similar except that this activity was not depressed in the mid-term pregnant rats.     

Interactions of hepatotoxic agents with proteins and subcellular structures

Two proteins with high affinity for amatoxins have been characterized in calf thymus nucleic, the RNA-polymerase II (or B) and a 100 K protein of unknown function. Most of the toxic effects of amatoxins are based on the inhibited synthesis of mRNA. The 100 K protein may be involved in functions of cytokinesis as suggested by experiments with PtK1 cells and a fluorescent labelled amatoxin. The molecular toxicity of phallotoxins can be understood in terms of their affinity for actin. By interaction with rabbit muscle actin the concentration of action monomers is decreased. In hepatocytes, the phallotoxins change the structure of the microfilamentous web.     

Effects of 2(3)-tert-butyl-4-hydroxyanisole administration on the activities of several hepatic microsomal and cytoplasmic enzymes in mice.

Administration of 2(3)-tert-butyl-4-hydroxyanisole (BHA) (0.75%) caused a marked increase in the activities of several hepatic enzymes in CD-1 mice. This was associated with increased liver weights and total protein contents, especially of the microsomal and cytosol fractions. While the specific content of cytochrome P-450 was decreased slightly in microsomes, the specific content of cytochrome b₅ and the specific activities of cytochrome c reductases (NADPH- or NADH-dependent) were increased (2-fold). In spite of a slight decrease in the specific activities of aminopyrine demethylase and of benzo(a)pyrene hydroxylase, both aniline hydroxylase and UDP-glucronyltransferase activities were increased (2.7- and 4.6-fold respectively). The specific activity of a microsomal membrane marker enzyme, glucose-6-phosphatase, was decreased slightly (?25 per cent). In the cytosol fraction, the specific activities of glucose-6-phosphate dehydrogenase and of UDP-glucose dehydrogenase were increased (3.8- and 6.1-fold respectively). Differences were noted in the time cources of increase and decrease in these enzyme activities after initiation and discontinuation of BHA treatment.     

Plasma levels of parent drug and metabolites in the intravenous aminopyrine breath test

Summary [Dimethylamine-¹⁴C]-aminopyrine was given i.v. to 5 healthy volunteers and 5 medical patients in a dose of 1.67 mg/kg, containing 0.02 µCi/kg ¹⁴C. In 4 volunteers the experiment was repeated using oral administration of aminopyrine. Exhalation of ¹⁴CO₂ was followed for 6–10 h and plasma levels of the drug and of its metabolites 4-methylamino-antipyrine, 4-amino-antipyrine, 4-acetylamino-antipyrine and 4-formylamino-antipyrine, were measured by thin-layer chromatography. The concentration-time profiles of the metabolites mostly failed to conform to a Bateman function. Areas under the curves from 1 to 6 h after dosing indicated distinct interindividual differences in metabolite patterns even in the absence of disturbed liver function, whereas the intraindividual data were closely reproducible. In most subjects, the area of 4-formylamino-antipyrine exceeded that of the acetyl analogue. The metabolite patterns did not exhibit a consistent relationship to the ratios between ¹⁴CO₂ half-life in breath and aminopyrine half-life in plasma, which varied from 1.4 to 3.2.     

Toxicity of methylmercury chloride in rats III. Long-term toxicity study

Four groups, each of 25 male and 25 female weanling rats, were given dietary levels of 0, 0.1, 0.5 and 2.5 ppm MeHgCl for 2 years. Observations were made on behaviour, growth, food intake, haematology, serum enzymes, urinalysis, microsomal liver enzymes, organ weights and histology with special reference to the nervous system, hitochemistry of the kidneys and cerebellum and on tissue Hg concentrations.Significant findings included a slight growth reduction in females at 2.5 ppm, increased relative kidney weight at 2.5 ppm and histochemical changes in kidney enzymes at 2.5 ppm. No effect was seen on the nature or incidence of pathological lesions or tumours at any level.From the results obtained in the short-term, reproduction and long-term studies, the no-toxic effect level for rats appears to be between 0.1 and 0.5 ppm MeHgCl in the diet.Exposure of the Dutch population does not appear to present a health hazard at the moment because the mean intake of total Hg is still far below the intake deemed to be safe.     

Effects of disulfiram on mixed function oxidase system and trace element concentration in the liver of rats

Disulfiram (DSF), an inhibitor of chemically induced carcinogenesis, and its metabolite diethyldithiocarbamate (DDTC) have been investigated for their influence on trace element distribution and on certain enzymes of the drug metabolizing system in the livers of phenobarbital (PB) treated rats. Both substances diminished the PB induced enzyme response in liver microsomes, DDTC being more effective (?85%) than DSF (?60%). The copper, cobalt and zinc content of the livers of DSF treated animals were increased by factors of 6, 3 and 1.5 respectively as compared to controls, while DDTC treatment had no influence on liver trace element content. A correlation between enzyme inhibition and enhanced trace element uptake of the liver after DSF administration could not be observed. The change of trace element transport into the liver during DSF treatment is discussed.     

Dose dependence of the14C-aminopyrine breath test

Summary Although the aminopyrine breath test has received much attention, the question has not yet been settled whether pharmacological or tracer doses of the drug should be used. Nine volunteers were given¹⁴C-aminopyrine 9 mg/kg or a tracer amount, in a randomized sequence and according to a crossover design. The specific activity of¹⁴CO₂ in breath was significantly different only during the first hour. Up to the 8th hour the disappearance of¹⁴CO₂ from breath was smaller after the pharmacological (28.5±SD 5.4%/h) than after the tracer dose (36.2±10.6%/h; p<0.05). The overall disappearance of¹⁴C-atoms from the subjects was significantly slower after the higher dose. In view of the smaller radiation exposure and the decreased risk of agranulocytosis, the use of a tracer dose appears preferable.Supported by the Swiss National Science Foundation     

Preparation of cells from pig gastric mucosa

Cells were isolated from pig gastric mucosa by a combination of mechanical and enzymatic treatment. Isopycnic centrifugation on linear density gradients of Percoll provided a simple and rapid procedure for obtaining highly enriched parietal cells and chief cells. Their densities were 1.06 and 1.10 g/ml, respectively. Isolated mucosal cells attached to Petri dishes coated with fibronectin or collagen. Both parietal cells and chief cells adhered more readily to fibronectin than collagen. Mucosal cells and cells from the Percoll gradients were maintained for up to one week as primary cell cultures. The ability of free parietal cells to produce acid was tested by the ¹⁴C-aminopyrine accumulation technique. Maximal accumulation was 2.5 pmol aminopyrine per 10⁴ parietal cells after incubation for 45 min at 10^-4 M histamine. The EC₅₀ for histamine was 5times10^-6 M.The accumulation of aminopyrine at 10^-6 M carbachol and 10^-7 M pentagastrin were for both secretagogues about 0.9 pmol per 10⁴ parietal cells.