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1.
青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究 总被引:1,自引:0,他引:1
将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5~4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。 相似文献
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Chromosome 11p15.5 regional imprinting: comparative analysis of KIP2 and H19 in human tissues and Wilms' tumors 总被引:9,自引:1,他引:9
The imprinted H19 gene is frequently inactivated in Wilms' tumors (WTs)
either by chromosome 11p15.5 loss of heterozygosity (LOH) or by
hypermethylation of the maternal allele and it is possible that there might
be coordinate disruption of imprinting of multiple 11p15.5 genes in these
tumors. To test this we have characterized total and allele- specific mRNA
expression levels and DNA methylation of the 11p15.5 KIP2 gene in normal
human tissues, WTs and embryonal rhabdomyosarcoma (RMS). Both KIP2 alleles
are expressed but there is a bias with the maternal allele contributing
70-90% of mRNA. Tumors with LOH show moderate to marked reductions in KIP2
mRNA relative to control tissues and residual mRNA expression is from the
imprinted paternal allele. Among WTs without LOH most cases with H19
inactivation also have reduced KIP2 expression and most cases with
persistent H19 expression have high levels of KIP2 mRNA. In contrast to the
extensive hypermethylation of the imprinted H19 allele, both KIP2 alleles
are hypomethylated and WTs with biallelic H19 hypermethylation lack
comparable hypermethylation of KIP2 DNA. 5-aza-2'-deoxycytidine (aza-C)
increases H19 expression in RD RMS cells but does not activate KIP2
expression. These data indicate coordinately reduced expression of two
linked paternally imprinted genes in most WTs and also suggest mechanistic
differences in the maintenance of imprinting at these two loci.
相似文献
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Objective To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. Methods The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation. 相似文献
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Derjung M. Tarn Debora A. Paterniti Neil S. Wenger 《Journal of general internal medicine》2016,31(8):909-917
BACKGROUND
Little is known about how providers communicate recommendations when scientific uncertainty exists.OBJECTIVES
To compare provider recommendations to those in the scientific literature, with a focus on whether uncertainty was communicated.DESIGN
Qualitative (inductive systematic content analysis) and quantitative analysis of previously collected audio-recorded provider–patient office visits.PARTICIPANTS
Sixty-one providers and a socio-economically diverse convenience sample of 603 of their patients from outpatient community- and academic-based primary care, integrative medicine, and complementary and alternative medicine provider offices in Southern California.MAIN MEASURES
Comparison of provider information-giving about vitamin D to professional guidelines and scientific information for which conflicting recommendations or insufficient scientific evidence exists; certainty with which information was conveyed.RESULTS
Ninety-two (15.3 %) of 603 visit discussions touched upon issues related to vitamin D testing, management and benefits. Vitamin D deficiency screening was discussed with 23 (25 %) patients, the definition of vitamin D deficiency with 21 (22.8 %), the optimal range for vitamin D levels with 26 (28.3 %), vitamin D supplementation dosing with 50 (54.3 %), and benefits of supplementation with 46 (50 %). For each of the professional guidelines/scientific information examined, providers conveyed information that deviated from professional guidelines and the existing scientific evidence. Of 166 statements made about vitamin D in this study, providers conveyed 160 (96.4 %) with certainty, without mention of any equivocal or contradictory evidence in the scientific literature. No uncertainty was mentioned when vitamin D dosing was discussed, even when recommended dosing was higher than guideline recommendations.CONCLUSIONS AND RELEVANCE
Providers convey the vast majority of information and recommendations about vitamin D with certainty, even though the scientific literature contains inconsistent recommendations and declarations of inadequate evidence. Not communicating uncertainty blurs the contrast between evidence-based recommendations and those without evidence. Providers should explore best practices for involving patients in decision-making by acknowledging the uncertainty behind their recommendations.10.
L. C. K. Low E. Y. W. Kwan Y. J. Lim A. C. W. Lee C. F. Tarn K. S. L. Lamf 《Clinical endocrinology》1995,42(4):359-363
OBJECTIVE Despite regular transfusion and desferoxamine treatment, growth failure Is commonly seen In adolescent children with β-thalassaemla major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We Investigated the effect of GH on short non-GH deficient children with β-thalassaemia. DESIGN Recombinant human GH was given In a dose of 0-14IU/kg/day subcutaneously in an open study. PATIENTS Fifteen prepubertal Chinese children with β-thalassaemia major (ranging from 7.16 to 14.7 years In age) with height ?1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response >15mlU/l to insulin Induced hypoglycaemia and normal thyroid function and adrenal reserve. MEASUREMENTS Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosa-mine levels were assessed at entry and every 3 months during treatment. Fasting Insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment. RESULTS Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and In one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6±0.7 cm/year to 8±1.2 cm/year after one year of GH treatment (P<0.001). IGF-I was low before treatment (10.1±2.7nmol/l), rising significantly to 15.8±4.8, 18.4±4.6, 19.3±6.4 and 21.9±7.5nmol/l at 3, 6, 9 and 12 months of treatment (P<0.005). The mean pretreatment bone age in the 13 children was 9.58±1.41 years and increased to 10.53±1.43 years after one year of treatment (ΔBA/CA 0.95±0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment. CONCLUSION Growth failure In these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensltlvity. Supraphyslologlcal doses of exogenous GH can cause a significant increase In serum IGF-I levels and a significant Improvement in short-term growth of short children with β-thalassaemia major. 相似文献