Collagen Cross-Linking for the Treatment of Fungal Keratitis

Objective: To evaluate whether corneal collagen cross-linking improves the outcome of fungal keratitis. Methods: This was a retrospective clinical study. Patients (n=82) with fungal infected eyes were treated at Affiliated Xiamen Eye Center of Xiamen University, from November 2011 to December 2017. Corneal cross-linking was performed using the standard protocol after a multi-antifungal drug treatment failed to resolve the infection in patients. Main outcome measures: Clinical symptoms and corneal healing were examined using a slit lamp biomicroscope and an in vivo laser confocal microscope. Visual acuity improvement was also evaluated. Results: After 6 months to 3 years of follow-up, corneal scars eventually developed in 71 of 82 eyes. In 52 of 82 eyes, visual acuity improved. However, corneal melting was exacerbated and uncontrolled in 8 patients who immediately underwent corneal transplant surgery. In one patient, self-conjunctival transplantation was performed, and two others received a therapeutic corneal transplant due to recurrent inflammation and melting. Conclusions: Our results demonstrate that corneal collagen cross-linking is an effective procedure to manage patients afflicted with fungal keratitis.     

SMILE联合快速角膜交联术后角膜光密度的早期临床观察

目的 观察飞秒激光小切口角膜基质透镜取出术联合快速角膜胶原交联术(SMILE Xtra)对角膜光密度的影响.方法 收集2017年3月至2019年7月在济南明水眼科医院矫正近视及近视散光的患者78例,纳入右眼数据(78眼)进行分析,根据手术方式分为SMILE Xtra组和SMILE组,其中SMILE Xtra组39例(3...     

Effects of Cross‐Link Density on Structures and Properties of Dual‐Sensitive Semi‐Interpenetrating Polymer Networks Hydrogel Microspheres

Semi‐interpenetrating polymer network (semi‐IPN) strategy is employed to fabricate uniform microspheres with temperature and pH dual‐responsive behavior, which is composed of poly(N‐isopropylacrylamide) and poly(acrylic acid) in the presence of N ,N ′‐methylenebisacrylamide (MBA) as the cross‐linker. The influences of MBA amount (M _m) on the structures and properties of the microspheres are investigated in terms of particle size, surface morphology, pH sensitivity, and thermo‐sensitivity with low critical solution temperature in the range M _m = 2.5–15%. Additionally, functional group distributions in the microspheres are probed by titration and employing the Henderson–Hasselbalch equation. The results show that all the properties strongly change depending on M _m. Based on transmission electron microscopy and confocal laser scanning microscopy measurements, and these properties, the M_m‐induced changes in the structures of the semi‐IPN microspheres are discussed.

     

AGE‐modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age‐related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end‐product (AGE)‐dependent non‐enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C‐type lectin‐like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin‐based contractility [myosin‐light chain‐2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE‐modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180^{ΔEx2–6/ΔEx2–6} mice, with constitutively exposed CTLD2 and decreased survival of men with early (non‐invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE‐dependent modification of the basal lamina induces invasive behaviour in non‐transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

准分子激光原位角膜磨镶术后角膜扩张的研究现状

准分子激光原位角膜磨镶术(LASIK)是日趋完善的一种角膜屈光手术,术后角膜扩张是其隐匿但严重的并发症,仍是屈光手术之后面临的最复杂和广泛讨论的问题之一.因此,LASIK术后角膜扩张的发病原因、危险因素及其预防和治疗有重要的现实意义.现对这些方面的研究现状作一综述.     

An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin

Abstract

The use of pectin for colon-specific drug delivery has been extensively investigated; however, when used alone, pectin is often compromised due to its high solubility. This study explored the feasibility of using an in situ compression-coated crosslinking system, composed of pectin and calcium chloride, for colon-specific drug delivery. A pectin/calcium chloride (P/Ca) coating was compressed onto a core tablet. The colon specificity of the compression-coated tablet was verified by dissolution, pharmacokinetics and scintigraphy with ^99mTc labeling. The in situ pectin and calcium chloride gel slowed the release of indomethacin. The lag time varied between 3?h and 7?h depending on the amount of calcium chloride and the coating weight. Pectinase triggered the release of indomethacin from the compression-coated tablet, which was then accelerated by the calcium chloride in the coating layer. The compression-coated tablet had a prolonged t_max and apparent t_1/2, as well as a decreased C_max and AUC_0–t, compared with the core tablet counterpart. Evaluation with γ-scintigraphy verified colon-specific delivery of the compression-coated tablet. In conclusion, the P/Ca in situ crosslinking system worked well for colon-specific drug delivery.     

The binding of glu- and lys-plasminogens to fibrin and their subsequent effects on fibrinolysis

The affinities of glu- and lys-plasminogens (plgn) for totally crosslinked fibrin were compared in two systems: a) incorporation into fibrin during clotting and b) direct adsorption onto fibrin immersed in plgn solution. Over a wide range of concentrations of plgn, uptakes were greater with incorporation than immersion, and in purified than in plasma systems. In all cases lys-plgn showed a greater affinity for fibrin than did glu-plgn. The potencies of glu- and lys-plgn were also compared in lysis systems using ¹²⁵I-labelled fibrin. The lysis achieved increased in proportion to the plgn concentrations to which clots were exposed. Fibrin to which plgn was adsorbed by immersion lysed slowly and incompletely when transferred to streptokinase (SK), irrespective of the type of plgn used. However, more lysis was achieved after incorporation of plgn, in which system prior exposure to lys-plgn gave more lysis in SK than did glu-plgn. In contrast, a third and slightly more potent lysis system (adsorbing SK-activator to washed fibrin then transferring the fibrin to plgn solution, called the SK→plgn regimen), produced marginally more lysis in glu- than lys-plgn. The molecular species of fibrin degradation products obtained with different lysis regimens were not altered by interchanging glu- and lys-plgns. Again, with either type of plgn, the binding to fibrin (in both incorporation and immersion systems) and the lysis rates of fibrin (in the SK→plgn regimen), were both decreased in the presence of plasma or serum. The pertinence of these test-tube data to $\text{in vivo}$ requirements for thrombolytic therapy is speculative, but they support both current theories that the impetus to fibrinolysis is provided a) by intrinsic plgn and b) by the adsorption of plgn activator to fibrin. It cannot be assumed that lys-plgn must be more effective than glu-plgn in lysis systems because of superior affinity for purified fibrin, and in these studies the most active lysis was achieved when either type of plgn percolated the fibrin and was activated to plasmin in situ.     

Reversal by Concanavalin A of the inhibitory effects of extracellular Ca2+ on pinocytosis in Amoeba proteus

When Concanavalin A, 1–20 μg ml^-1 binds to the surface of Amoeba proteus the cell's response to Ca²⁺ and to cationic inducers of pinocytosis is strikingly altered. Separately, Concanavalin A and Ca²⁺ are weak inducers but their combined effects are intense pinocytosis and suppression of the normal inhibitory effect of Ca²⁺ on cation-induced pinocytosis. At high concentrations (> 25 μg ml^-l) the lectin increases cellular uptake and binding of ⁴⁵Ca in the cell surface but the ionic permeability and the potential of the cell membrane are little changed by treatment with Concanavalin A. Subsequent addition of Ca²⁺ starts the pinocytic cycle and causes a fivefold increase of the membrane resistance without depolarizing the cell. Neither a rise of free intracellular calcium nor an influx of ⁴⁵Ca preceeds formation of pinocytotic channels when Con A is applied to cells in the presence of calcium. All effects of Concanavalin A are blocked by α-methylmannoside while succinyl-Concanavalin A is without effects on pinocytosis. These findings suggest that crosslinking of cell surface carbohydrates reverses calcium inhibition of pinocytosis and increases the cell's pinocytotic response to cations without modifying either the bioelectrical effects or the intracellular free concentration of calcium.