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61.
Preclinical Research
A number of N‐benzoylindoles were designed and synthesized as deaza analogs of previously reported potent and selective HNE inhibitors with an indazole scaffold. The new compounds containing substituents and functions that were most active in the previous series were active in the micromolar range (the most potent had IC50 = 3.8 μM) or inactive. These results demonstrated the importance of N‐2 in the indazole nucleus. Docking studies performed on several compounds containing the same substituents but with an indole or an indazole scaffold, respectively, highlight interesting aspects concerning the molecule orientation and H‐bonding interactions, which could help to explain the lower activity of this new series. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.  相似文献   
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铅对作业工人甲状腺功能的影响   总被引:4,自引:0,他引:4  
目的 了解铅对作业工人甲状腺功能的影响。方法 选择暴露于铅作业环境下的人群 ,了解工人作业工龄 ,采用火焰原子吸收光谱法测定其作业环境中铅浓度 ,用原子吸收光谱法测定作业工人血铅 (PbB)浓度 ,用血液锌原卟啉测定仪测定血锌原卟啉 (ZPP)浓度 ,用放射免疫分析法检测血清中促甲状腺素 (TSH)、三碘甲状腺原氨酸 (T3)、甲状腺素 (T4 )、游离T3(FT3)、游离T4 (FT4 ) 5项甲状腺功能指标。结果 血铅 >2 .88μmol/L时 ,T3[(1 .54± 0 .39)nmol/L]、FT3[(5 .50± 1 .2 6)pmol/L]含量明显低于血铅 (1 .92~ 2 .88) μmol/L组 [T3(1 .71± 0 .45)nmol/L、FT3(6 .1 2± 1 .64)pmol/L] ,差异有显著性(P <0 .0 5)。铅作业工龄长短对甲状腺激素 (TH)含量未见明显影响。结论 高浓度血铅可能抑制了T4 的脱碘 ;铅作业工龄对甲状腺功能未见明显影响  相似文献   
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OBJECTIVE The aim of this study was to provide a comprehensive benchmark of 30-day ventriculoperitoneal(VP)shunt failure rates for a single institution over a 5-year study period for both adult and pediatric patients,to compare this with the results in previously published literature,and to establish factors associated with shunt failure.METHODS A retrospective database search was undertaken to identify all VP shunt operations performed in a single,regional neurosurgical unit during a 5-year period.Data were collected regarding patient age,sex,origin of hydrocephalus,and whether the shunt was a primary or secondary shunt.Operative notes were used to ascertain the type of valve inserted,which components of the shunt were adjusted/replaced(in revision cases),level of seniority of the most senior surgeon who participated in the operation,and number of surgeons involved in the operation.Where appropriate and where available,postoperative imaging was assessed for grade of shunt placement,using a recognized grading system.Univariate and multivariate models were used to establish factors associated with early(30-day)shunt failure.RESULTS Six hundred eighty-three VP shunt operations were performed,of which 321 were pediatric and 362 were adult.The median duration of postoperative follow-up for nonfailed shunts(excluding deaths)was 1263 days(range 525-2226 days).The pediatric 30-day shunt failure rates in the authors'institution were 8.8%for primary shunts and 23.4%for revisions.In adults,the 30-day shunt failure rates are 17.7%for primary shunts and 25.6%for revisions.In pediatric procedures,the number of surgeons involved in the operating theater was significantly associated with shunt failure rate.In adults,the origin of hydrocephalus was a statistically significant variable.Primary shunts lasted longer than revision shunts,irrespective of patient age.CONCLUSIONS A benchmark of 30-day failures is presented and is consistent with current national databases and previously published data by other groups.The number of surgeons involved in shunt operations and the origin of the patient's hydrocephalus should be described in future studies and should be controlled for in any prospective work.The choice of shunt valve was not a significant predictor of shunt failure.Most previous studies on shunts have concentrated on primary shunts,but the high rate of early shunt failure in revision cases(in both adults and children)is perhaps where future research efforts should be concentrated.  相似文献   
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目的 对兴安白芷进行系统的生药学研究以区别于其他白芷类药材.方法 按照常规生药学方法进行来源、性状、显微鉴定,按<中国药典>2005年版白芷项下方法进行薄层鉴别与含量测定.结果 找出了兴安白芷在生药性状、组织构造及化学成分上的主要特征.结论 为白芷种质资源的评价提供了参考依据.  相似文献   
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ObjectiveTo investigate the neurotransmitter enzyme Acetylcholinesterase (AChE) activity in the brain and blood of rats infected with Trypanosoma congolense (T. congo).MethodsPresence and degree of parasitemia was determined daily for each rat by the rapid matching method. AChE activity was determined by preparing a reaction mixture of brain homogenate and whole blood with 5, 5-dithiobisnitrobenzioc acid (DTNB or Ellman's reagent) and Acetylthiocholine (ATC). The increase in absorbance was recorded at 436 nm over 10 min at 2 min intervals. Trypanosome species identification (before inoculation and on day 10 post infection) was done by Polymerase chain reaction using specific primers.ResultsThe AChE activity in the brain and blood decreased significantly as compared with the uninfected control. The AChE activity dropped to 0.32 from 2.20 μmol ACTC min?1mg protein?1 in the brain and 4.57 to 0.76 μmol ACTC min-1mg protein?1 in the blood. The animals treated with Diminaveto at 3.5 mg/kg/d were observed to have recovered significantly from parasitemia and were able to regain AChE activity in the blood but not in the brain as compared to the control groups. We also observed, that progressive parasitemia resulted to alterations in PCV, Hb, RBC, WBC, neurophils, total protein, lymphocytes, monocytes and eosinophil in acute infections of T. congo. Polymerase chain reaction (PCR) of infected blood before inoculation and on day 10 post infection revealed 600 bp on agarose gel electrophoresis.ConclusionsThis finding suggest that decrease in AChE activity increases acetylcholine concentration in the synaptic cleft resulting to neurological failures in impulse transfer in T. congo infection rats.  相似文献   
69.
The nitric oxide pathway in pre-eclampsia: pathophysiological implications   总被引:2,自引:0,他引:2  
Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with NG-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined.  相似文献   
70.
A 57-year-old-man with a history of malaise, fever,night sweats and shortness of breath presented a diagnostic challenge to his medical team. He was pancytopaenic and had splenomegaly on admission but other investigations, including bone marrow aspiration, proved inconclusive. After the patient deteriorated clinically, the general surgical team was requested to perform a diagnostic splenectomy. The histology of this showed infection with visceral leishmaniasis. He recovered completely with Amphotericin treatment. Although this is a rare condition, particularly for the general surgeon, this case highlights the difficult position surgeons are often put in when performing major surgery diagnostically.  相似文献   
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