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51.
Predictivity of an in vitro model for acute and chronic skin irritation (SkinEthic) applied to the testing of topical vehicles 总被引:2,自引:0,他引:2
A. de Brugerolle de Fraissinette V. Picarles S. Chibout M. Kolopp J. Medina P. Burtin M.E. Ebelin S. Osborne F. K. Mayer A. Spake M. Rosdy B. De Wever R.A. Ettlin A. Cordier 《Cell biology and toxicology》1999,15(2):121-135
An in vitro human reconstructed epidermis model (SkinEthic) used for screening acute and chronic skin irritation potential
was validated against in vivo data from skin tolerability studies. The irritation potential of sodium lauryl sulfate (SLS),
calcipotriol and trans-retinoic acid was investigated. The in vitro epidermis-like model consists of cultures of keratinocytes
from human foreskin on a polycarbonate filter. The modulation of cell viability, the release and gene expression of proinflammatory
cytokines, interleukins 1α and 8, and morphological changes were evaluated during 3 days as endpoints representative for an
inflammatory reaction. The cumulative irritation potential of the topical products was evaluated in a human clinical study
by visual scoring and biophysical measurement of inflammatory skin reaction after repeated 24 h applications over 3 weeks
under Finn chamber patches. All topical products that were nonirritating in the human study were noncytotoxic and did not
induce cytokine expression in the in vitro acute model (day 1 exposure). All irritating controls exhibited specific cell viability
and cytokine patterns, which were predictive of the in vivo human data. The ranking of mild to moderate skin irritation potential
was based on the lack of cytotoxicity and the presence of cytokine patterns including gene expression specific for each irritant,
using the chronic in vitro model (up to 3 days exposure).
The human reconstructed epidermis model SkinEthic was shown to be a reliable preclinical tool predicting the irritation potential
of topical products. Moreover, it is a useful model in a two-step tiered strategy for screening acute and chronic irritation
potential for the selection of vehicles for new topical drugs.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
52.
Louise Shaxson 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1526):2141-2151
How can we strengthen the science–policy interface for plastics, the environment and human health? In a complex policy area with multiple stakeholders, it is important to clarify the nature of the particular plastics-related issue before trying to understand how to reconcile the supply and demand for evidence in policy. This article proposes a simple problem typology to assess the fundamental characteristics of a policy issue and thus identify appropriate processes for science–policy interactions. This is illustrated with two case studies from one UK Government Department, showing how policy and science meet over the environmental problems of plastics waste in the marine environment and on land. A problem-structuring methodology helps us understand why some policy issues can be addressed through relatively linear flows of science from experts to policymakers but why others demand a more reflexive approach to brokering the knowledge between science and policy. Suggestions are given at the end of the article for practical actions that can be taken on both sides. 相似文献
53.
54.
Eun Jin Park Joon Young Song Min Ju Choi Ji Ho Jeon Jah-yeon Choi Tae Un Yang Kyung Wook Hong Ji Yun Noh Hee Jin Cheong Woo Joo Kim 《The Korean journal of parasitology》2014,52(4):425-428
A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia. 相似文献
55.
Abhishek Chatterjee Celia Caballero-Franco Dannika Bakker Stephanie Totten Armando Jardim 《The Journal of biological chemistry》2015,290(42):25579-25594
Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280–320-kDa oligomeric structure consisting of ∼6–7 subunits. 相似文献
56.
A.S. Purewal 《FEMS microbiology letters》1991,82(2):229-232
The nucleotide sequence of the gene specifying the ethidium efflux system of Escherichia coli has been determined. The translated open reading frame has identified a membrane-bound polypeptide of 110 amino acids (11,960 Da) which shares 42% identity with a staphylococcal protein specifying resistance to ethidium. 相似文献
57.
人睫状神经营养因子的原核表达,纯化及其生物效应 总被引:2,自引:0,他引:2
人睫状神经营养因子(hCNTF)克隆入pBV220中,在DH5α菌株中表达,重组蛋白以包含体的形式存在,表达量为菌体总蛋白的50%左右。经比较发现用2mol/L脲洗涤包含体可溶解大量可溶性细菌蛋白,且包含体损失较小。在高浓度变性剂条件下进行sepharcylS-200凝胶过滤,解决了纯化中hCNTF易聚合的问题,在低浓度变性剂条件下进行DEAE离子交换,有利于蛋白活性的保持。经两步纯化后得到均一性hCNTF,纯度达95%以上。在自然状态下使hCNTF复性。纯化复性后的hCNTF对无血清培养的鸡胚背根节神经元和脊髓腹角运动神经元有明显的维持存活和促进生长发育的生物效应。 相似文献
58.
59.
60.
《Cytokine》2015,74(2):245-252
BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 109/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 109/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention. 相似文献