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1.
Rajendrababu Sharmila Puthuran George Varghese Alia Laxmi Ananya Uduman Mohammed Sithiq Wijesinghe Hiruni Kaushalya 《International ophthalmology》2022,42(8):2609-2618
International Ophthalmology - To investigate the efficacy and safety of non-valved Aurolab aqueous drainage implant (AADI) surgery combined with phacoemulsification in eyes with refractory glaucoma... 相似文献
2.
Norfloxacin and ofloxacin are two frequently prescribed second-generation fluoroquinolone antibiotics with an identical 4-quinolone chromophore and hence, are difficult to distinguish by conventional methods (UV or fluorescence). We have designed a Tb3+/Eu3+/cholate cocktail that enabled us to differentiate these two drugs and rapidly measure their concentrations when present together. Additionally, a Tb3+-cholate gel-based paper sensor was developed to detect and quantify them in a single drug containing system with a limit of detection (LOD) well below 100 nM.Rapid distinction of structurally similar fluoroquinolone antibiotics norfloxacin and ofloxacin, and their quantification in a mixture, were achieved using a supramolecular Tb/Eu gel cocktail.Fluoroquinolone antibiotics belong to one of the most important classes of human and veterinary medicines owing to their broad-spectrum activity and effective oral absorption. Norfloxacin and ofloxacin (Fig. 1) are among the most prescribed second generation fluoroquinolone antibiotics1,2 used for the treatment of respiratory and urinary tract infections, ocular and skin infections, pelvic inflammatory disease, gonococcal urethritis, infectious diarrhoea, etc. However, potential adverse reactions such as tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, hematuria, and central nervous system effects due to their excess intake have been well documented in the literature.3 Extensive use and misuse of the antibiotics as veterinary medicines have led to their appearance in milk,4,5 chicken6 and fish7 imposing adverse side effects for the consumer. Contamination of municipal wastewater, surface water and even groundwater results from their extensive usage, and from their excretion from human and animals unchanged.8 All these can cause the propagation of antibiotic-resistant micro-organisms9 leading to a disturbed ecosystem. Therefore, the development of a robust, rapid and straightforward analytical protocol for screening of Norfloxacin (NFLX) and Ofloxacin (OFLX) residues in biological fluids, sewage water, edible tissues and foodstuff is highly desirable for the control of their appropriate dosage, maintaining their pharmacokinetics and avoid environmental crisis.10 Various analytical methods for this purpose have been reported in the literature including spectrophotometry,11 spectrofluorimetry,12 voltammetry,13,14 capillary electrophoresis,15 chemiluminescence,16,17 and high performance liquid chromatography (HPLC).18 Several fluorescent probes have utilized molecular imprinting chemiluminescence,19 Neodymium-modified micellar media,20 carbon dots etc.21,22 Although fluorescence-based reporters provide greater intrinsic sensitivity, many of them are, however, incompatible with biological samples because of complications arising from background scattering and autofluorescence from endogenous components.23 Trivalent lanthanide ions have long radiative lifetimes allowing background-free measurement using time-gating. They also have sharp, well-defined long-wavelength emission fingerprints24 ideal for biological applications and can therefore serve as a strong sensing platform. They can be sensitized by proximate chromophores (‘‘antennae’’) and may act as attractive fluorogenic (turn on) and fluorolytic (turn-off) bio-probes. This group has extensively investigated photoluminescent lanthanide cholate supramolecular hydrogels25–32 by utilizing their in-built hydrophobic pockets to encapsulate small organic ‘antennas’. The self-assembly brings the antenna in close proximity to the acceptor lanthanide leading to energy transfer to the lanthanide ion. This strategy thus eliminates the need for the synthesis of antenna-linker-ligand type of probes to achieve lanthanide sensitization. A variety of lanthanide-luminescence based fluoroquinolone-assays17,33–38 have been reported in the literature. However, tedious synthesis of the probe, complex sample treatments, non-aqueous detection media, strict maintenance of pH have restricted the practical applicability of many of them.34–37 We have found that when doped in micromolar concentrations in Tb-Ch (5/15 mM) or Eu-Ch (5/15 mM) gels, both Norfloxacin and Ofloxacin significantly enhanced the luminescence intensities. Based on this finding we explored cholate-hydrogel based detection and quantification of these two fluoroquinolones. Initial experiments were performed in Tb (5 mM) cholate (15 mM) hydrogel by doping it with increasing concentrations of norfloxacin (NFLX). The emission intensity of Tb3+ showed a linear relationship with concentration (Fig. S1 in ESI†). Even 4 μM of NFLX resulted in 30-fold enhancement of sensitization of Tb3+ luminescence. Atomic force microscopy showed that the fibrous network of Tb3+-cholate gel remained unaltered (Fig. S2 in ESI†) when NFLX was doped in micromolar concentrations, proving the robustness and stability of the sensing gel system. Fluorescence microscopic image of semi-dried NFLX doped Tb-cholate gel (Fig. S2c in ESI†) showed uniform green luminescent gel fibres, indicating that the NFLX was distributed and embedded on the hydrophobic fibres, promoting the energy transfer process making the fibres green luminescent.Open in a separate windowFig. 1Structures of Norfloxacin and Ofloxacin.In order to simplify the sensing method, we chose a paper-based system. Such sensors39–41 are affordable, biodegradable, sensitive, specific, user-friendly, rapid, robust, and deliverable to end-users. For this purpose, Tb-cholate (5/15 mM) gel doped with NFLX (4 μM) was prepared, sonicated for 5–6 s to reduce the viscosity, and then applied (20 μL) on a 3 mm paper disc (Fig. 2). SEM images showed dried flakes of gel on the cellulose fibre network (Fig. S3 in ESI†). The thickness of the gel layer coated on the paper surface was about 8 μm, as determined by tilt-SEM (Fig. S3c in ESI†). Time gated fluorescence (TRF) was measured on the coated discs using a plate reader. After 5 min of drying, a significantly higher Tb3+ luminescence output was observed, compared to that measured in wet gels (Fig. 3b, 8 vs. 7). This increase may be attributed to the efficient wicking of water molecules from the gel in the hydrophilic cellulose frameworks of paper which in turn helps reduce the OH-mediated luminescence quenching.42 Increased sensitization on gel-coated paper discs was observed for both NFLX and OFLX. We also confirmed that the extent of sensitization of Tb3+ remained constant as a function of time (Fig. S4 in ESI†). The limit of detection (LOD) for NFLX and OFLX were measured based on Tb3+-luminescence output as a function of the drug concentration and were found to be 13.6 nM (Fig. S5a in ESI†) and 67 nM (Fig. S5b in ESI†), respectively. The paper-based method was used to quantify the NFLX spiked in milk samples (cow raw milk and a commercial homogenized toned milk) and in human blood serum. The LOD values measured were 68 nM, 100 nM and 100 nM, respectively (Fig. S12 and S13 in SI†). The time-gated detection method eliminated any interference from the matrix (serum or milk). This method is therefore simple, rapid, sensitive, autofluorescence and background emission free, and may thus serve as a practical tool for analytical screening.Open in a separate windowFig. 2Design of paper-based sensors (paper disc cutting, placing them on plate groove, gel dropcasting).Open in a separate windowFig. 3Tb3+ -luminescence (λem 545 nm, λex 330 nm) enhancement by NFLX (4 μM) (Ac, Ch, D: acetate solution, cholate matrix and coated paper disc, respectively).Distinguishing two structurally similar compounds of the same class is a fundamental objective of analytical research.Dennany et al. recently reported a [Ru(bpy)3]2+ based ECL sensor43 to distinguish Atropine and Scopolamine, two similar alkaloids. Encouraged by this report, we focused on the differentiation of norfloxacin and ofloxacin which have comparable 4-quinolone chromophores with similar functional groups attached (Fig. 1). With both drugs, the luminescence enhancement for Tb3+ was greater than that for Eu3+ (Fig. S8 & S9 in ESI†). Therefore, single lanthanide (Tb3+ or Eu3+) derived gels cannot differentiate them. For this purpose, heterobimetallic ensemble strategy was explored by adopting the ratiometric detection technique.44,45 In order to identify optimum conditions, a set of five cholate gels samples containing varying ratios of Tb3+ & Eu3+ (maintaining total concentration of 5 mM) was prepared. This set was doped with 1 μM NFLX. An identical set was prepared with 1 μM OFLX as the dopant. After drop casting the gels on paper discs, luminescence intensities were quantified on a plate reader (Fig. 4a and b). From these data, the sensitization bias ITb/IEu, as measured by I545/I617 (λex 330 nm), was calculated and plotted against the concentration of Tb3+ in the mixed gel. Tb3+/Eu3+ cocktail with [Tb3+] ≥ 2.5 mM doped with NFLX showed sensitization bias (I545/I617) values greater than 1, whereas with OFLX the bias was always less than 1 (Fig. 4c). Based on these observations we chose Tb3+/Eu3+/cholate (4.5 mM/0.5 mM/15 mM) cocktail as the probe to differentiate these two drugs over a wider concentration range (Fig. S15 in ESI†). Another set of measurements were made at low μM concentrations of the drugs (Fig. S14 in ESI†). The Terbium sensitization bias (ITb/IEu) was calculated and plotted against the concentration of FLXs and found to be greater than 1 for NFLX but less than 1 for OFLX (Fig. S14c in ESI†). In the Tb3+/Eu3+ mixed cholate hydrogel matrix three concurrent energy transfer processes can occur–energy transfer from sensitizer (i) to Tb3+, (ii) to Eu3+, and (iii) energy transfer from Tb3+ to Eu3+. While one of the emission bands of Tb3+ has overlap with the most intense 617 nm peak of Eu3+, the Eu3+ emission peak at 690 nm is solely contributed by Eu3+. The 690 nm emission intensity in 15 μM NFLX doped mixed gels was measured and found to linearly increase with the Tb3+ concentration (even though Eu3+ concentration is decreasing) indicating Tb3+– Eu3+ energy transfer (Fig. S19 in ESI†). Significant reduction of Tb3+-luminescence lifetime from 1.53 ms in NFLX doped Tb3+-Ch (4.5 mM/15 mM) gel to 0.55 ms in NFLX doped Tb3+/Eu3+-Ch (4.5 mM/0.5 mM/15 mM) gel provided additional evidence. In the Tb3+/Eu3+/cholate (4.5 mM/0.5 mM/15 mM) cocktail, the three concurrent energy transfer processes are optimized to show Tb3+/Eu3+ emission intensity ratio exactly reversed for the two drugs (Fig. S14, S16 in ESI†). The optimized cocktail was subsequently used to determine the ratio of the two drugs in a mixture. The drug mixtures (total concentration 20 μM) were doped in the cocktail and the photophysical behavior was investigated. The excitation spectra corresponding to Eu3+ 617 nm emission showed a unique pattern depending on the ratio of NFLX and OFLX in the mixture. The intensity (Fig. 5a) at 280 nm reflects NFLX excitation, whereas the intensity at 300 nm reflects OFLX excitation. Based on these findings, the Eu3+ emission intensity at 617 nm from the drug mixtures at two different excitation wavelengths 280 nm and 300 nm were evaluated. Ratiometric response I617 (λex 280)/I617(λex 300) was found to linearly increase with the ratio of NFLX concentration to the total concentrations of both the drugs in the mixture (Fig. 5c). To validate the need for using the cocktail in this study, the excitation spectra corresponding to Eu3+ at 617 nm in (NFLX + OFLX) doped Eu3+-Ch gel (no Tb) was recorded in which no such NFLX & OFLX ratio-dependent pattern was observed (Fig. S17 in ESI†). For further exploration of the cocktail, Terbium emission sensitization bias was calculated and found to be directly proportional to the ratio of NFLX concentration to the total concentrations of both the drugs in the mixture (Fig. 6b). This protocol can thus be used as a platform to determine the ratio and individual concentration of the two drugs when present in a mixture.Open in a separate windowFig. 4Emission intensities from Tb3+ at 545 nm and Eu3+ at 617 nm (λex 330 nm of 1 μM (a) NFLX and (b) OFLX doped mixed cholate {[Tb3+] + [Eu3+] = 5 mM} gel coated discs for varying ratios of Tb3+& Eu3+ (c) Terbium sensitization bias I545/I617 (λex 330 nm) as a function of Tb3+ concentration.Open in a separate windowFig. 5(a) Excitation spectra for Eu3+ emission (λem 617 nm) with respect to the ratio of two drugs (b) Intensity of Eu3+ emission at 617 nm for two excitation wavelengths (280 nm, 300 nm) in Tb3+/Eu3+/cholate (4.5 mM/0.5 mM/15 mM) gel coated discs with increasing concentrations of NFLX in a mixture of OFLX & NFLX, (c) intensity ratio plotted against the concentration of NFLX in the mixture.Open in a separate windowFig. 6(a) Tb3+ emission at 545 nm and Eu3+ emission 617 nm (b) Tb3+ sensitization bias in Tb3+/Eu3+/cholate (4.5 mM/0.5 mM/15 mM) gel coated discs with the ratio of NFLX concentration to the total drug concentration in the mixture (λex 330 nm).In conclusion, a hetero bimetallic ensemble Tb3+/Eu3+/cholate was designed for the differentiation of structurally similar NFLX and OFLX. Till date, only physical separation by HPLC is known to quantify norfloxacin and ofloxacin concentrations in a mixture. Additionally, a paper-based sensor has also been developed for the detection and quantification of them in single drug containing system with a lower nanomolar range. The method allowed autofluorescence free detection with biological samples without the need of deproteinization and sample processing. Nonetheless, our preliminary investigations employed to utilize ratiometric bis-lanthanide strategy will serve as the foundation for the fundamental need to differentiate structurally similar molecules. Further studies to utilize this supramolecular paper-based methodology in real diagnostic fields is underway in our lab. 相似文献
3.
Ananya Dutta Mithun Thulasidas Ajita Sasidharan Balam Pradeep V Rajesh Prabu 《Indian journal of ophthalmology》2022,70(12):4146
Purpose:To assess the association between radial peripapillary capillary (RPC) plexus using optical coherence tomography angiography (OCTA) and retinal nerve fibre layer (RNFL) thickness using spectral domain OCT (SD-OCT) in primary open-angle glaucoma (POAG) patients, glaucoma suspects, and healthy subjects.Methods:In this single-centre cross-sectional observational study, POAG, glaucoma suspects, and healthy patients underwent OCT-RNFL and optic nerve head angiography scans. The RNFL thickness and the vascular parameters obtained from RPC plexus, including perfusion density (PD), flux index (FI), and vessel density (VD), were analysed.Results:In all, 120 eyes of 120 patients, including 40 POAG patients, 40 glaucoma suspects, and 40 healthy subjects, were included. The pairwise comparison of mean RNFL thickness, FI, and VD showed significant difference (P < 0.001) in all sectors between POAG, glaucoma suspects, and healthy eyes. However, PD showed no significant difference between glaucoma suspects and healthy eyes. The average RNFL thickness was found to have a better diagnostic ability than VD to distinguish POAG eyes from healthy eyes and glaucoma suspects based on receiver operating characteristics curve and area under the curve. VD had better diagnostic accuracy than RNFL when glaucoma suspects and healthy were compared.Conclusion:OCT-RNFL has better diagnostic capability in differentiating glaucoma from healthy eyes compared to OCTA. However, OCTA was found to be better in screening out glaucoma suspects from healthy eyes. The VD is a better OCTA parameter than FI and PD to differentiate POAG and glaucoma suspects from healthy eyes. 相似文献
4.
Nguyen Thuy T. Ngo Lan Q. Promsudthi Ananya Surarit Rudee 《Clinical oral investigations》2017,21(7):2345-2353
Clinical Oral Investigations - The study aimed at assessing oxidative stress (OS) biomarker levels in the saliva of patients with chronic periodontitis (CP) and acute coronary syndrome (ACS) and... 相似文献
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7.
Maladaptive daydreaming (MD) is an immersive fantasy activity that leads to distress and socio-occupational dysfunction. MD has many features suggestive of behavioural addiction, but research exploring the phenomenology of this clinical construct is limited. MD has also been purported to be a maladaptive strategy to cope with distress, but often leads to uncontrollable absorption in fantasy world, social withdrawal and neglected aspects of everyday life. In this paper, we report the case of a 16-year-old boy who developed internet gaming disorder and MD after experiencing cyberbullying from his peers. The patient engaged in vivid, fanciful imagery that lasted for hours, leading to social dysfunction and academic deterioration. Baseline assessment revealed a Maladaptive Daydreaming Scale-16 score of 65 (cut-off 50) and an Internet Gaming Test-20 score of 86 (cut-off 71). The patient was managed primarily with psychological intervention. The therapy focused on behaviour modification and cognitive restructuring. Patients in clinical setting should be questioned about MD when presenting with excessive use of technology or other forms of behavioural addictions. Further studies are necessary to determine the biopsychosocial factors of MD and its correlates. There is also a need to study treatment and management approaches for treating MD. 相似文献
8.
Lynsey J Hamlett Andrew J McPartlin Edward J Maile Gareth Webster Ric Swindell Carl G Rowbottom Ananya Choudhury Adam H Aitkenhead 《The British journal of radiology》2015,88(1054)
Objective:
We investigated possible associations between planned dose–volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy.Methods:
For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose–volume (DVH), dose–surface (DSH) and dose–line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose–surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann–Whitney U test.Results:
Associations (p < 0.05) were found between equieffective dose (EQD23) and late toxicity as follows: overall toxicity with DVH and DSH at 13–24 Gy; proctitis with DVH and DSH at 25–36 Gy and with DVH, DSH and DLH at 61–67 Gy; bowel urgency with DVH and DSH at 10–20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction.Conclusion:
Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose–toxicity comparisons.Advances in knowledge:
This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions. 相似文献9.
10.
Isenberg G Sivak MV Chak A Wong RC Willis JE Wolf B Rowland DY Das A Rollins A 《Gastrointestinal endoscopy》2005,62(6):825-831
BACKGROUND: Endoscopic optical coherence tomography (EOCT) is a high-resolution, cross-sectional tissue-imaging technique that provides microscopic morphologic information. EOCT should detect dysplasia in Barrett's epithelium, but this has not been established in a prospective blinded study. This study evaluated the accuracy of EOCT for the diagnosis and the exclusion of dysplasia in patients with Barrett's esophagus. METHODS: A 2.4-mm diameter EOCT probe was modified for use with a cap-fitted, two-channel endoscope. Pairs of EOCT image streams and jumbo biopsy specimens were obtained. Endoscopy/EOCT procedures were performed by 4 endoscopists who separately reviewed the EOCT digital images for the absence or the presence of dysplasia (low grade, high grade, or cancer) for each biopsy specimen obtained. The endoscopists were blinded to the interpretation of the pathology. An experienced pathologist blinded to the endoscopic/EOCT findings evaluated each biopsy for the absence or the presence of dysplasia. The setting of the study was a major academic medical center. Adult patients with documented Barrett's esophagus greater than 2 cm were included in the study. The main outcome measurement was the accuracy of EOCT in the detection of dysplasia in patients with Barrett's esophagus. RESULTS: A total of 314 usable EOCT image stream/biopsy pairs were obtained in 33 patients. By using histology as the standard, the performance of EOCT was sensitivity, 68%; specificity, 82%; positive predictive value, 53%; negative predictive value, 89%; and diagnostic accuracy, 78%. Diagnostic accuracy for the 4 endoscopists ranged from 56% to 98%. Limitations of the study were the variability in endoscopists' accuracy rates, difficulty in real-time interpretation, and the need for refined criteria of dysplasia by EOCT imaging. CONCLUSIONS: The current EOCT system has an accuracy of 78% for the detection of dysplasia in patients with Barrett's esophagus. EOCT could be used to target biopsies to areas of Barrett's epithelium with a higher probability for the presence of dysplasia. However, further modifications, including increased resolution and identification of further potential OCT characteristics of dysplasia, are needed before EOCT can be used clinically. 相似文献