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141.
Belete A Desimmie Michael Humbert Eveline Lescrinier Jelle Hendrix Sofie Vets Rik Gijsbers Ruth M Ruprecht Ursula Dietrich Zeger Debyser Frauke Christ 《Molecular therapy》2012,20(11):2064-2075
The interaction between the human immunodeficiency virus (HIV) integrase (IN) and its cellular cofactor lens epithelium-derived growth factor (LEDGF/p75) is crucial for HIV replication. While recently discovered LEDGINs inhibit HIV-1 replication by occupying the LEDGF/p75 pocket in IN, it remained to be demonstrated whether LEDGF/p75 by itself can be targeted. By phage display we identified cyclic peptides (CPs) as the first LEDGF/p75 ligands that inhibit the LEDGF/p75–IN interaction. The CPs inhibit HIV replication in different cell lines without overt toxicity. In accord with the role of LEDGF/p75 in HIV integration and its inhibition by LEDGINs, CP64, and CP65 block HIV replication primarily by inhibiting the integration step. The CPs retained activity against HIV strains resistant to raltegravir or LEDGINs. Saturation transfer difference (STD) NMR showed residues in CP64 that strongly interact with LEDGF/p75 but not with HIV IN. Mutational analysis identified tryptophan as an important residue responsible for the activity of the peptides. Serial passaging of virus in the presence of CPs did not yield resistant strains. Our work provides proof-of-concept for direct targeting of LEDGF/p75 as novel therapeutic strategy and the CPs thereby serve as scaffold for future development of new HIV therapeutics. 相似文献
142.
Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed. 相似文献
143.
144.
Roy Patterson Irena M. Suszko Stephen G. Hendrix C.Raymond Zeiss 《The Journal of allergy and clinical immunology》1981,67(2):162-165
Aqueous extracts of tree pollen were partially purified and polymerized with methods previously established for preparation of ragweed and grass polymers. The polymerized tree preparations were antigenic as demonstrated by ability to elicit immediate-type skin reactivity in humans and to induce an immune response in rabbits. The polymerized tree antigen was 100- to 10,000-fold less skin reactive than monomer tree antigen in tree pollen-sensitive patients but both preparations had similar antigenicity in rabbits. These results demonstrate that polymerized tree antigens can be prepared and should have the therapeutic potential already demonstrated for polymerized ragweed preparations. 相似文献
145.
Jennifer L Leiting Jordan M Cloyd Ahmed Ahmed Keith Fournier rew J Lee Sophie Dessureault Seth Felder Jula Veerapong Joel M Baumgartner Callisia Clarke Harveshp Mogal Charles A Staley Mohammad Y Zaidi Sameer H Patel Syed A Ahmad Ryan J Hendrix Laura Lambert Daniel E Abbott Courtney Pokrzywa Mustafa Raoof Christopher J LaRocca Fabian M Johnston Jonathan Greer Travis E Grotz 《World journal of gastrointestinal oncology》2020,12(7):756-767
146.
The inter‐rater reliability between nurse‐assessors clinically assessing infection of chronic wounds using the WUWHS criteria 下载免费PDF全文
Jacqueline JHHM Vestjens Armand ALM Rondas Richard RJ White Samantha SL Holloway 《International wound journal》2018,15(1):8-15
The aim of this study was to determine the inter‐rater reliability between one expert‐nurse and four clinical‐nurses who were asked to clinically assess infection of chronic wounds by using the World Union of Wound Healing Societies (WUWHS) criteria. A quasi‐experimental design was used to collect the data. In comparison to phase 1 in which ‘open questions’ were asked, in phase 2 a pre‐printed form (checklist) was introduced. In both phases, 55 chronic wounds were clinically assessed. For each WUWHS criterion the inter‐rater reliability of signs and symptoms was expressed by Cohens Kappa (κ). A substantial agreement (κ ≥ 0·6) was considered as adequate. In both phases pocketing (p < 0·02), and erythema (p < 0·004) scored statistically significant results. Phase 2 showed higher inter‐rater agreements compared with phase 1 (three substantial agreements (easily bleeding/friable granulation tissue, delayed healing, increasing exudate), an almost perfect‐ and a perfect agreement for malodour and pain, respectively. According to the results it can be concluded that the clinical assessment of infection of chronic wounds may be better supported by a pre‐printed form than making use of an ‘open questions’ form. To provide this with a higher level of evidence, there is need for more well conducted studies. 相似文献
147.
Scanning electron microscopy and electron probe microanalysis studies are reported on thin sections of calcified coacervates
of α-elastin. It is found that the capacity of elastin coacervates to initiate calcification is a bulk property of the coacervate
and not limited to the serum-coacervate interface, that the calcium phosphate deposits act to bind the protein units together
and slow the dissolution and spreading of the coacervate as it floats on an air-water interface, and that, within the limits
of detectability, there is no involvement of sulfur. As the charged groups of α-elastin had been blocked, the initiation of
deposition is due to neutral sites in the protein which are tightly bound to the calcium phosphate deposits. 相似文献
148.
What we have learned from the myriad trials 总被引:2,自引:2,他引:0
149.
高效液相色谱法测定消痰咳片的含量 总被引:2,自引:0,他引:2
目的:采用反相色谱法同时测定消痰咳片中两种主要成分甲氧苄啶和磺胺体的含量。方法:以乙腈:0.1%H3PO4(15:85)为流动相,检测波长254nm,HPLC法测定含量。结果:试验表明,甲氧苄啶和磺胺林在0.8-8ug范围内呈良好的线性关系,回归方程分别为Y=-1127.1+110.2x(r=0.9994),Y=-1852.3 256.2x(r=0.9996),相对标准偏差分别为2.1%和0.8%。结论:该方法简便、准确、可靠。 相似文献
150.
目的:考察5种注射剂盐酸林可霉素注射液,盐酸精氨酸注射液,注射用玻璃酸酶,肝素钠注射液和顺铂注射液的细菌内毒素检查法可行性。方法:中国药典细菌内毒素检查法。结果;除d外,其余原液及稀释液均于有干扰作用。结论:d的原液及a的20倍以上稀释液可用灵敏度为0.5EU/ml的鲎试剂作细菌内毒素检查,而b,c和e尚需进一步探讨。 相似文献