BackgroundContact lens related keratitis is a frequent presentation to acute ophthalmology services. Patients often do not recall being counselled regarding the safe use of contact lenses therefore fail to comply with guidance.This study aimed to identify the content and format of advice given to patients with contact lens keratitis concerning appropriate hygiene practices, determine their compliance with this and finally characterise optometrist practices regarding contact lens advice provided to patients.MethodsAll adult patients presenting with contact lens related keratitis to the acute ophthalmology clinic were asked to complete a survey. Information was collected on lens type, format of advice received and compliance.Community optometrists were asked to complete an electronic survey on their contact lens review practices and routine patient education.ResultsAll patients surveyed recalled counselling on initiation of contact lenses; however 12% (6/50) were given no advice on return visits. This advice was in written format for 20% (10/50) of patients on initiation increasing to 32% (16/50) on renewal.Many patients slept (22%), showered (44%) or swam (36%) in lenses. 92% cleaned their contact lenses appropriately, but cases were washed infrequently (19% of cases cleaned < monthly) or with tap water (27%).All optometrists surveyed claimed to provide advice to patients in either written or verbal format for new and returning contact lens users. 49% (16/33) of optometrists gave written advice to patients on initial contact lens fitting, but only 1/33 continued with written advice for repeat customers.ConclusionThis study identified that although most patients were informed of appropriate hygiene requirements, compliance was poor. Optometrists regularly provide verbal advice but do not routinely offer written support and there is a mismatch between patient recollection and self-reported optometrist practice. It is suggested that patient education needs greater emphasis and both verbal and written information should be regularly provided on initial review and follow up assessments. 相似文献
Support vector machines (SVM) and other machine-learning (ML) methods have been explored as ligand-based virtual screening (VS) tools for facilitating lead discovery. While exhibiting good hit selection performance, in screening large compound libraries, these methods tend to produce lower hit-rate than those of the best performing VS tools, partly because their training-sets contain limited spectrum of inactive compounds. We tested whether the performance of SVM can be improved by using training-sets of diverse inactive compounds. In retrospective database screening of active compounds of single mechanism (HIV protease inhibitors, DHFR inhibitors, dopamine antagonists) and multiple mechanisms (CNS active agents) from large libraries of 2.986 million compounds, the yields, hit-rates, and enrichment factors of our SVM models are 52.4–78.0%, 4.7–73.8%, and 214–10,543, respectively, compared to those of 62–95%, 0.65–35%, and 20–1200 by structure-based VS and 55–81%, 0.2–0.7%, and 110–795 by other ligand-based VS tools in screening libraries of ≥1 million compounds. The hit-rates are comparable and the enrichment factors are substantially better than the best results of other VS tools. 24.3–87.6% of the predicted hits are outside the known hit families. SVM appears to be potentially useful for facilitating lead discovery in VS of large compound libraries. 相似文献
Modified carboxymethyl chitosan (CMC) containing phosphatidylethanolamine (PEA) groups were synthesized by a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated coupling reaction. The structure of the modified CMC exhibiting an amphiphilic character was analysed by FT-IR and 1H NMR. CMC-g-PEA beads were prepared with sodium tripolyphosphate (TPP) by ionic-crosslinking. The beads sizes were in range from 800 to 1200 μm and encapsulation efficiencies of drug were more than 68%. The morphologies of CMC-g-PEA beads were examined with scanning electron microscopy (SEM). The release experiments were performed using ketoprofen as an hydrophobic model drug. The drug dissolution kinetics showed longer release times for CMC-g-PEA beads: 20 h (at pH 1.4) and 45 h (at pH 7.4). The amount of the drug release was much higher in acidic solution than in basic solution due to the swelling properties of the matrix at acidic pH. These results suggest that modified CMC with PEA may become a potential delivery system to control the release of hydrophobic drugs. 相似文献
Medicinal chemists are facing an increasing challenge to deliver safer and more effective medicines. An appropriate balance between drug-like properties such as solubility, permeability, metabolic stability, efficacy and toxicity is one of the most challenging problems during lead optimization of a potential drug candidate. Insoluble and impermeable compounds can result in erroneous biological data and unreliable SAR in enzyme and cell-based assays. The weak inhibitory activity and non-drug-like properties of monastrol, the first small mitotic kinesin Eg5 inhibitor, has hampered its further development. In this investigation, a bioisosteric approach was applied that resulted in the replacement of C-5 carbonyl of monastrol with thio-carbonyl. Further lead optimization of drug-like properties was evaluated through in silico predictions by using ADMET predictor software. This minor structural modification resulted in upgraded human effective jejunal permeability (Peff) and improved permeability in Madin–Darby canine kidney (MDCK) cells. Furthermore, C-5 thiocarbonyl analogue of monastrol (named as Special-2) was found safe to administer orally with no phospholipidosis toxicity, no raised levels of serum glutamate oxaloacetate transaminase (SGOT) and no potential towards cardiotoxicity. Molecular docking study was also carried out to understand the binding modes of these compounds. The docking study showed high binding affinity of the designed compounds against KSP. Hence a combination of in silico ADMET studies and molecular docking can help to improve prediction success and these compounds might be act as potential candidate for KSP inhibition. 相似文献
Aim: The purpose of this study was to investigate the detailed mechanisms of oral absorption enhancement of bergenin (BN) using BN–phospholipid complex (BPC).
Methods: Multiple models such as ex vivo everted rat gut sac model and in vitro Caco-2 cell model were used. Meanwhile, the effect of chitosan on the enhancement of the permeability of BPC was evaluated.
Results: The limited absorption of BN was significantly improved in both ex vivo everted rat gut sac model and in vitro Caco-2 cell model when combined with phospholipid. The transport of BPC was uppermost 5.19-fold higher than that of BN. The results of ex vivo everted rat gut sac model showed that small intestine was a more suitable site for the absorption of BN and BPC than colon. Passive diffusion was the only way employed in the transport of BN, while BPC could transport across enterocytes by both passive diffusion and active transport which was found to be the clathrine-dependent receptor-mediated endocytosis. The absorption of BN was barely improved by the physical mixture of BN and phospholipid due to lack of stable intermolecular interactions. Moreover, the addition of chitosan could open the tight junctions of intestinal epithelial cells, thus significantly increasing the transport of BPC via paracellular route.
Conclusions: Totally different mechanisms, which led to the enhanced oral bioavailability, were utilized in the uptake and transport process of BPC compared with BN. These results would be of significance for the future development of oral delivery systems of BN. 相似文献
Bone-like apatite formation on porous calcium phosphate ceramics was investigated in static simulated body fluid (SBF) and dynamic SBF at different flowing rates. The results of a 14-day immersion in static SBF showed that the formation of bone-like apatite occurred both on the surface and in the pores of the samples. When SBF flowed at the physiological flow rate in muscle (2 ml/100 ml⋅min), bone-like apatite could be detected only in internal surface of the pores of samples. The result that bone-like apatite formation could only be found in the pores when SBF flowed at physiological flow rate was consistent with that of porous calcium phosphate ceramics implanted in vivo: osteoinduction was only detected inside the pores of the porous calcium phosphate ceramics. This result implicates that the bone-like apatite may play an important role in the osteoinduction of Ca-P materials. The dynamic model used in this study may be better than usually used static immersion model in imitating the physiological condition of bone-like apatite formation. Dynamic SBF method is very useful to understand bone-like apatite formation in vivo and the mechanism of ectopic bone formation in calcium phosphate ceramics. 相似文献