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Pemirolast potassium ocular in situ gels are safe and promising therapeutic alternatives to the existing medications for allergic conjunctivitis therapy.
The incidence of fungal infection after corneal transplant has increased significantly in recent years, especially
spp. This study aimed to evaluate the efficacy and safety of the addition of cycloheximide in Optisol-GS media in decreasing the growth of
spp. strains.
This in vitro laboratory efficacy study measured fungal colony growth in 24 vials of Optisol-GS that were divided into 6 groups of 4 vials each, as follows (1) MIC/2 cycloheximide, (2) MIC cycloheximide, (3) MICx5 cycloheximide, (4) MICx10 cycloheximide, from MIC values obtained for each strain, (5) unsupplemented optisol-GS as a positive control (added inoculum), and (6) unsupplemented optisol-GS as a negative control (no inoculum). In each group was added
and
, except in the negative control. The evaluated variables were fungal colony growth from the Optisol-GS vials, corneal endothelial cell density and endothelial cell viability at different concentrations of cycloheximide.
In the efficacy study, all strains showed a reduction in fungal cell growth from the second day at all evaluated concentrations of optisol-GS supplemented with cycloheximide, even at subinhibitory concentrations (MIC/2). For
, the colony count was reduced to 99%. No evidence of corneal endothelial toxicity was found at any concentration, in the safety study, compared with the paired control.
The addition of cycloheximide to optisol-GS decreased the fungal growth, demonstrating fungicide action against
and fungistatic action against
and
. This drug did not demonstrate toxicity to the corneal endothelium at different concentrations.
The addition of cycloheximide to optisol-GS decreased the fungal growth, demonstrating fungicide action against C. glabrata and fungistatic action against C. albicans and C. parapsilosis. This drug did not demonstrate toxicity to the corneal endothelium at different concentrations.
One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM),
coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive.
Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA.
The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP.
Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.
Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.Chimeric antigen receptor (CAR) T cell therapy has achieved unrivalled success in the treatment of B cell and plasma cell malignancies, with five CAR T cell products now approved by the US Food and Drug Administration (FDA). However, CAR T cell therapies for solid tumours have not been nearly as successful, owing to several additional challenges. Here, we discuss mechanisms of tumour resistance in CAR T cell therapy and the emerging strategies that are under development to engineer CAR T cells to overcome resistance.Large B-cell lymphomas (LBCLs) constitute a subgroup of aggressive but highly curable lymphoproliferative diseases. Treatment of relapsed/refractory (R/R) patients still represents an unmet clinical need, and novel drugs and combinations are in continuous development. The pan-B cell panel of surface antigens that characterizes LBCL leads to a large umbrella of druggable targets. Monoclonal antibodies (mAbs) express their activity against lymphoma by targeting multiple tumor-specific antigens. This category consists of a number of molecules with different mechanisms of action, including naked mAbs, radioimmunoconjugates, antibody-drug conjugates, checkpoint inhibitors, and bispecific antibodies. In the last decade, apart from the well-known role of the anti-CD20 mAb rituximab, novel mAbs have led to remarkable steps forward in the treatment of R/R LBCL in monotherapy and combined with chemotherapy. Multiple studies are in development trying to bring these novel compounds into the frontline setting to empower the RCHOP effect or as alternative chemotherapy-free options for elderly/unfit patients. This review provides insight into antilymphoma mAbs, focused on the efficacy and safety of the main molecules approved or in development for LBCL andperspectives on the treatment of this disease.
To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI).
A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis.
In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis.
Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.
Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.
To investigate the association between the inclusion of components identified on images in target spots of photodynamic therapy (PDT) and exudate relapse in eyes with age-related macular degeneration (AMD).
Forty-one eyes (39 patients) with polypoidal choroidal vasculopathy (PCV) and 32 eyes (31 patients) with typical AMD (tAMD) who underwent PDT were retrospectively investigated. Each component identified on fluorescein (FA) or indocyanine angiography (IA), optical coherence tomography (OCT), or color photography was graded as not depicted, covered with a margin ≥500 µm or <500 µm, and protruding. Associations between these grades and the dry rate (proportion of subjects with continuous absence of exudate over following 12-month period) and the relapse index (2 × number of injections administered + accumulation of exudate for 12 months post-PDT) were investigated.
In PCV, the association between worse coverage and decreasing dry rates for feeder vessels and polyps approached statistical significanceriate targets, corresponding to the existing guidelines, and feeder vessels, classic lesion, occult lesion, and PED in PCV and CNV on IA in tAMD were suggested as further targets. OCT was superior to FA for evaluating PED.
Intracanalicular dexamethasone insert is a resorbable sustained-release polyethylene glycol-based hydrogel insert delivering a 0.4 mg tapered dose of dexamethasone for up to 30 days to the ocular surface. It is FDA-approved for treating inflammation and pain after ocular surgery. It has also been studied for ocular surface diseases such as allergic conjunctivitis. WZ811 concentration This study assessed the plasma pharmacokinetic (PK) parameters of dexamethasone following intracanalicular insertion.
Study subjects (N=16) were healthy adults. A dexamethasone insert was unilaterally placed into the canaliculus, and blood samples were obtained for analysis 1 hour prior to insertion and 1, 2, 4, 8, 16, 24 hours and 4, 8, 15, 22 and 29 days after insertion. Safety analyses included slit lamp and dilated fundus examinations, best corrected visual acuity, intraocular pressure (IOP) and adverse events (AEs).
Plasma results were below the lower limit of quantitation (LLOQ) at all time points in five subjects (31.3%). Among subjects with quantifiable plasma concentrations, C
was <1 ng/mL (range, 0.05 to 0.81 ng/mL), AUC
ranged from 0.13 to 7.18 h∙ng/mL, and T
ranged from 4.0 to 163.0 hours. Mean (SD) IOP increased from 16.3 (1.4) mmHg at baseline to 19.3 (3.2) at Day 22 but returned to baseline after treatment. No changes occurred in dilated fundus, punctum, or visual acuity examinations.
The dexamethasone 0.4 mg insert results in minimal systemic exposure following intracanalicular administration.
The dexamethasone 0.4 mg insert results in minimal systemic exposure following intracanalicular administration.The Yamane intrascleral flanged haptic fixation technique has obviated the need for resources such as suture or glue. However, intraocular maneuvers to properly dock haptics into the needles for externalization can be difficult for even adept eye surgeons and is especially difficult when visualization through the cornea is poor. Additionally, one traditional resource, intraocular forceps, has been critical in both the original technique and proposed modifications since its inception. We describe a modified flanged intrascleral intraocular lens fixation technique by docking the second haptic externally at the main corneal incision. This technique does not require the use of microforceps, which is advantageous to surgeons who lack access to specialized instrumentation. Additionally, this technique may provide added safety, visibility, and ease for surgeons by docking the haptic externally at the corneal incision rather than within the eye.