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《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
3.
《Burns : journal of the International Society for Burn Injuries》2021,47(5):1038-1044
IntroductionAlthough blood transfusion is common in burns, data are lacking in appropriate transfusion thresholds. It has been reported that a restrictive blood transfusion policy decreases blood utilization and improves outcomes in critically ill adults, but the impact of a restrictive blood transfusion policy in burn patients is unclear. We decided to investigate the outcome of decreasing the blood transfusion threshold.Material and methodsEighty patients with TBSA > 20% who met our inclusion criteria were included. They were randomly divided into control and intervention groups. The intervention group received packed cells only when Hemoglobin declined to less than 8 g/dL at routine laboratory evaluations. While the control group received packed-cell when hemoglobin was declined to less than 10 g/dl. The total number of the received packed cell before, during and after any surgical procedure was recorded. The outcome was measured by the evaluation of the infection rate and other complications.ResultThe mean hemoglobin level before transfusion was 7.7 ± 0.4 g/dL in the restrictive group and 8.8 ± 0.7 g/dL in the liberal group. The mean number of RBC unit transfusion per patient in the restrictive group was significantly lower than the traditional group (3.28 ± 2.2 units vs. 5.9 ± 3.7 units) (p-value = 0.006). The total number of RBC transfused units varied significantly between the two groups (p-value = 0.014). The number of transfused RBC units outside the operation room showed a significant difference between groups (restrictive: 2.8 ± 1.4 units vs. liberal: 4.4 ± 2.6 units) (p = 0.004). We did not find any significant difference in mortality rate or other outcome measures between groups.ConclusionApplying the restrictive transfusion strategy in thermal burn patients who are highly prone to all kinds of infection, does not adversely impact the patient outcome, and results in significant cost savings to the institution and lower rate of infection. We conclude that the restrictive transfusion practice during burn excision and grafting is well tolerated and effective in reducing the number of transfusions without increasing complications.Clinical Trial Registration ReferenceIRCT20190209042660N1. 相似文献
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L Mettler 《JSLS, Journal of the Society of Laparoendoscopic Surgeons》2002,6(4):305-309
BACKGROUND AND OBJECTIVES: Evaluation of long-term results using a thermal balloon endometrial ablation technique to treat menorrhagia and hypermenorrhea, considered dysfunctional uterine bleedings. METHODS: A single-arm, prospective study with long-term follow-up of 48 months at the department of obstetrics and gynecology, University of Kiel, Germany. Following hysteroscopic evaluation of the uterine cavity and fractionated curettage, the Cavaterm endometrial thermal ablation technique was performed on 70 patients over the age of 40 with menorrhagia and hypermenorrhea in whom medical treatment had previously failed. The study included a group of 10 patients with adenomyosis and uterine fibroids. RESULTS: In 65 patients, a complete 48-month follow-up evaluation was possible: 58% of patients reported amenorrhea and 33% hypomenorrhea. Nine percent of patients remained eumenorrheic. Fifty percent of the small group with failed indications for the procedure had to undergo a hysterectomy. CONCLUSIONS: The Cavaterm thermal coagulation system in the earlier mode of application (15 minutes at a temperature of 70 degrees C and a pressure of 200 mm Hg) is a safe and highly effective method of endometrial ablation resulting in a minimal amount of posttreatment menstrual bleeding. 相似文献
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妇科腹腔镜手术几种激光对兔子宫壁损伤的实验研究 总被引:2,自引:2,他引:0
为掌握妇科腹腔镜手术所应用的激光器的治疗剂量,对几种激光引起的兔子宫壁热损伤进行观察。实验研究证实:所有激光产生的损伤程度与所用的剂量呈正相关。术后48h与即刻损伤程度相比,半导体激光的损伤程度明显加深、加宽;但CO2激光和NdYAG激光接触式光刀无显著变化。说明应用激光行妇科腹腔镜手术治疗时,所产生的损伤与应用的功率密度有关,为临床合理选用腹腔镜下的激光治疗提供依据 相似文献
8.
M. Guillemin H. Cachier C. Chini D. Dabill D. Dahmann F. Diebold A. Fischer H.-H. Fricke J. A. Groves R. Hebisch M. Houpillart G. Israël M. Mattenklott W. Moldenhauer J. P. Sandino C. Schlums E. Sutter E. Tucek 《International archives of occupational and environmental health》1997,70(3):161-172
Object: Diesel soot has been recognized as probably carcinogenic to humans. Elemental carbon (also called black carbon) in soot
is considered at the moment as the most significant surrogate to be measured for assessing the exposure to this pollutant.
Its analysis is done by combustion in an oven and determination of the CO2 formed, after elimination of the organic fraction of the soot by heating and/or by solvent extraction. The analysis allows
determination of both fractions of the soot: “elemental carbon” (EC) and organic carbon␣(OC). The sum of EC and OC is called
TC (total carbon). Method: An informal European coordination group organized two round robin tests on filter samples collected from diluted diesel
emissions. The first round (RRT1) was performed on 13 different samples analyzed by ten laboratories. The range of loading
was 2.5 to 150 μg/cm2 of EC. No evaluation of the precision within laboratories could be made since each laboratory gave only one result per sample.
Therefore a second round (RRT2) was organized with two samples and a blank filter sent in several portions to 11 laboratories.
It should be stressed that each laboratory used its own method and that no standardization was planned at this stage. Results: Results of RRT1 showed that the coefficient of variation between laboratories decreased with higher loading and was around
10% to 15% for EC above about 20 μg/cm2. Dispersion of the results varied and it appeared that the way OC is removed from the soot is probably the most important
factor of influence. The correlation between the laboratories was good as a whole but some systematic differences could be
detected. Besides the different techniques to remove the organic carbon, the pretreatment of the filter by HCl (either as
a vapor or as a solution) to remove the inorganic carbonates (potential interference sources), is probably also a significant
factor of influence in the dispersion of the results between laboratories. It is not yet clear from these results whether
the “environmental” laboratories give different results from the “occupational” laboratories, but it is clear that their objectives
differ since for the “environmentalists”, EC is not a specific marker of diesel immissions, in contrast to the “occupationalists”.
Conclusion: It can be concluded that, although significant differences exist between laboratories they can be attributed mainly to the
narrow distribution of the results within a single laboratory, and that the overall agreement of the results for EC and TC
is fairly good. These results obtained with pure diesel engine emissions, should be complemented by field samples, but they
have already achieved relevant findings in the performance of the procedures used to assess exposure to diesel soot.
Received: 30 December 1996 / Accepted: 21 February 1997 相似文献
9.
High energy laser has emerged to be an important surgical tool in medical technology. However, the application of laser energy
to drill or cut a bone is still in an experimental state. In order to estimate the adequacy of laser heating of bone surface
and at the same time minimize the damage to the bone tissue, we developed a mathematical model of the temperature distribution
in bone due to laser irradiation. The thermal analysis shows that the temperature distribution depends on several parameters,
including the density, the specific heat, and the thermal conductivity of the osseous tissue. 相似文献
10.
Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were
selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into
TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of
TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry
(DSC) was also investigated. Phase transition temperature (Tc) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, Tc of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM
was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near Tc and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine)
only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA)
on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below Tc. However, ADM release from TSL was increased at the near and above Tc. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near
Tc. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed,
the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs
to preheated target sites due to its thermal behaviors. 相似文献