Confocal microscopy findings in deep anterior lamellar keratoplasty performed after Descemet's stripping automated endothelial keratoplasty

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Pang A

2014-01-01

Full Text Available Audrey Pang,1,2 Karim Mohamed-Noriega,1 Anita S Chan,1,3–5 Jodbhir S Mehta1,3 1Singapore National Eye Centre, 2Department of Ophthalmology, Tan Tock Seng Hospital, 3Singapore Eye Research Institute, 4Department of Histopathology, Pathology, Singapore General Hospital, 5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Background: This study describes the in vivo confocal microscopy findings in two patients who had deep anterior lamellar keratoplasty (DALK following Descemet's stripping automated endothelial keratoplasty (DSAEK. Methods: The study reviewed the cases of two patients who first underwent DSAEK followed by DALK when their vision failed to improve due to residual stromal scarring. In the first case, a DSAEK was performed for a patient with pseudophakic bullous keratopathy. After surgery, the patient's vision failed to improve satisfactorily due to residual anterior stromal opacity and irregularity. Subsequently, the patient underwent a DALK. The same two consecutive operations were performed for a second patient with keratoconus whose previous penetrating keratoplasty had failed and had secondary graft ectasia. In vivo confocal microscopy was performed 2 months after the DALK surgery in both cases. Results: At 3 months after DALK, the best-corrected visual acuity was 6/30 in case 1 and 6/24 in case 2. In vivo confocal microscopy in both cases revealed the presence of quiescent keratocytes in the stroma layers of the DSAEK and DALK grafts, which was similar in the central and peripheral cornea. There was no activated keratocytes or haze noted in the interface between the grafts. Conclusion: Our short-term results show that performing a DALK after a DSAEK is an effective way of restoring cornea clarity in patients with residual anterior stromal opacity. In vivo confocal microscopy showed that there were no activated keratocytes seen in the interface of the grafts, which suggests

Indications for and techniques of keratoplasty at Vietnam National Institute of Ophthalmology

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Pham Ngoc Dong

2016-03-01

Full Text Available AIM: To report the indications for and techniques of corneal transplantation at Vietnam National Institute of Ophthalmology (VNIO over a period of 12y (2002-2013. METHODS: Records of patients who had undergone corneal transplantation at VNIO from January 1, 2002 to January 1, 2014 were reviewed to determine the indication for and type of corneal transplant performed. Patient age, gender, indication for corneal transplantation and surgical technique were recorded and analyzed. RESULTS: Corneal transplantation were underwent in 1390 eyes of 1278 patients with a mean age of 44.9±18.1y during the period under review. The most common indication was infectious corneal ulcer (n=670; 48.2%, followed by corneal scar (n=333, 24.0%, corneal dystrophy (n=138, 9.9% and failed graft (n=112, 8.1%. Nearly all procedures performed were penetrating keratoplasty (n=1300, 93.5%, with a few lamellar keratoplasty procedures performed: lamellar keratoplasty (n=52, 3.7%, Descemet’s stripping automated endothelial keratoplasty (n=27, 1.9% and deep anterior lamellar keratoplasty (n=11, 0.8%. CONCLUSION: While the most common indication for keratoplasty was infectious keratitis, nearly all indications for corneal transplantation were managed with penetrating keratoplasty. However, lamellar keratoplasty techniques, including deep anterior lamellar keratoplasty and Descemet’s stripping automated endothelial keratoplasty, are being performed with increasing frequency for isolated stromal and endothelial disorders, respectively.

Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

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Aruna K.R. Gupta

2016-01-01

Full Text Available Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK, 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK, 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05, while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV, i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained.

A simple rescue maneuver for unfolding and centering a tightly rolled graft in Descemet membrane endothelial keratoplasty

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Droutsas K

2014-10-01

Full Text Available Konstantinos Droutsas,1,2 Thomas Bertelmann,1 Frank M Schroeder,1 Dimitrios Papaconstantinou,2 Walter Sekundo1 1Department of Ophthalmology, Philipps University, Marburg, Germany; 2First Department of Ophthalmology, University of Athens, Medical School of Athens, Athens, Greece Abstract: A 74-year-old man underwent Descemet membrane endothelial keratoplasty (DMEK for endothelial decompensation due to Fuchs endothelial dystrophy. After descemetorhexis, the DMEK graft was inserted into the anterior chamber. However, unfolding of the graft was not possible as the graft was very tightly rolled together and the anterior chamber deep. After placing a 30G-cannula connected to an air-filled syringe inside the roll's lumen, a small air bubble was injected, which allowed the roll to open up, until it assumed a “taco” configuration around the bubble. Then, the graft was centered by pressing the posterior part of the roll against, and sweeping it over the iris. In the present case a “tight” DMEK roll was successfully unfolded by injection of a single air bubble into the roll’s lumen and centered by a “sweeping” the partialy unfolded graft over the iris. This technique allowed a controlled unfolding and centering of the DMEK graft with limited trauma to the donor endothelium and may be applied in cases where other less traumatic maneuvers are not successful. Keywords: Fuchs endothelial dystrophy, surgical technique, endothelial keratoplasty

Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Influence of the Graft-Host Junction on the Graft Survival Rate.

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Omoto, Takashi; Sakisaka, Toshihiro; Toyono, Tetsuya; Yoshida, Junko; Shirakawa, Rika; Miyai, Takashi; Yamagami, Satoru; Usui, Tomohiko

2018-04-01

To investigate the clinical results of Descemet stripping automated endothelial keratoplasty (DSAEK) for failed penetrating keratoplasty (PK) and the influence of the graft-host junction (GHJ) on the graft survival rate. Data were retrospectively collected on patient demographics, visual outcomes, complications, and graft survival rate for 17 eyes of 16 patients who underwent DSAEK for failed PK. The graft survival rate was compared between the eyes when divided into a bump group and a well-aligned group according to the shape of the GHJ detected on anterior segment optical coherence tomography. The most common indication for initial PK was bullous keratopathy after glaucoma surgery (35.3%). Seven eyes (41.2%) were classified into the bump group and 10 eyes (58.8%) into the well-aligned group. The mean best-ever documented visual acuity (BDVA) after DSAEK was 0.33 logMAR. Postoperatively, almost 70% of eyes achieved a BDVA that was within 0.2 logMAR of their preoperative BDVA. Graft detachment occurred in 29.4% of eyes and primary graft failure in 17.6%. All primary failures occurred in the bump group. The cumulative graft survival rate was 82.3% at 1 year, 73.2% at 2 years, and 58.6% at 3 years. Graft failure was more likely in eyes in the bump group than in those in the well-aligned group (P = 0.037, Wilcoxon test). DSAEK for failed PK had a favorable outcome in this study. However, the GHJ should be assessed carefully before performing the procedure.

Interface Fluid Syndrome After Laser In Situ Keratomileusis (LASIK) Because of Fuchs Endothelial Dystrophy Reversed by Descemet Membrane Endothelial Keratoplasty (DMEK).

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Luceri, Salvatore; Baksoellah, Zainab; Ilyas, Abbas; Baydoun, Lamis; Melles, Gerrit R J

2016-12-01

To describe a case that developed "interface fluid syndrome" after previous laser in situ keratomileusis (LASIK) because of Fuchs endothelial dystrophy (FED), which was reversed by Descemet membrane endothelial keratoplasty (DMEK). A 58-year-old male patient presented with bilateral visual impairment owing to FED and visually significant cataract. Cataract surgery was carried out in both eyes followed by DMEK in his left eye. After cataract surgery, visual acuity did not improve sufficiently because corneal thickness increased and a fine cleft with interface fluid developed between the LASIK-flap and the residual stromal bed. After uneventful DMEK in his left eye, the fluid resolved within a week and visual acuity improved rapidly. This case demonstrates that "interface fluid syndrome" after LASIK caused by concomitant endothelial dysfunction may be reversed by DMEK allowing fast visual recovery.

Electrospun nanofibrous SF/P(LLA-CL) membrane: a potential substratum for endothelial keratoplasty.

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Chen, Junzhao; Yan, Chenxi; Zhu, Mengyu; Yao, Qinke; Shao, Chunyi; Lu, Wenjuan; Wang, Jing; Mo, Xiumei; Gu, Ping; Fu, Yao; Fan, Xianqun

2015-01-01

Cornea transplant technology has progressed markedly in recent decades, allowing surgeons to replace diseased corneal endothelium by a thin lamellar structure. A thin, transparent, biocompatible, tissue-engineered substratum with corneal endothelial cells for endothelial keratoplasty is currently of interest. Electrospinning a nanofibrous structure can simulate the extracellular matrix and have beneficial effects for cell culture. Silk fibroin (SF) has good biocompatibility but poor mechanical properties, while poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) has good mechanical properties but poor biocompatibility. Blending SF with P(LLA-CL) can maintain the advantages of both these materials and overcome their disadvantages. Blended electrospun nanofibrous membranes may be suitable for regeneration of the corneal endothelium. The aim of this study was to produce a tissue-engineered construct suitable for endothelial keratoplasty. Five scaffolds containing different SF:P(LLA-CL) blended ratios (100:0, 75:25, 50:50, 25:75, 0:100) were manufactured. A human corneal endothelial (B4G12) cell line was cultured on the membranes. Light transmission, speed of cell adherence, cell viability (live-dead test), cell proliferation (Ki-67, BrdU staining), and cell monolayer formation were detected on membranes with the different blended ratios, and expression of some functional genes was also detected by real-time polymerase chain reaction. Different blended ratios of scaffolds had different light transmittance properties. The 25:75 blended ratio membrane had the best transmittance among these scaffolds. All electrospun nanofibrous membranes showed improved speed of cell adherence when compared with the control group, especially when the P(LLA-CL) ratio increased. The 25:75 blended ratio membranes also had the highest cell proliferation. B4G12 cells could form a monolayer on all scaffolds, and most functional genes were also stably expressed on all scaffolds. Only two genes

Fuchs' dystrophy associated with radial keratotomy: Lamellar or perforating keratoplasty?

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Rodriguez-Ausin, P; Antolin-Garcia, D; Santamaria Garcia, L; Blazquez-Fernandez, A-B

2017-05-01

A 70 year-old male patient with a history of radial keratotomy suffering from Fuchs' dystrophy and a cataract. The patient received a two-step surgery: lens phacoemulsification and intraocular lens implant, followed by descemet stripping automated endothelial keratoplasty in both eyes, four months later. There were no complications apart from a recurrent cystoid macular oedema in both eyes. The best corrected visual acuity was 20/40 both eyes, and the patient was satisfied. Descemet stripping automated endothelial keratoplasty may be considered as an alternative to penetrating keratoplasty in the case of endothelial dysfunction and radial keratotomy in patients with no corneal ectasia or significant stromal opacity. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Descemet membrane endothelial keratoplasty (DMEK) early stage graft failure in eyes with preexisting glaucoma.

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Treder, Maximilian; Alnawaiseh, Maged; Eter, Nicole

2017-07-01

To evaluate the effect of a preexisting glaucoma on the early postoperative outcome of a descemet membrane endothelial keratoplasty (DMEK). All patients who underwent DMEK surgery at the Department of Ophthalmology of the University of Muenster with a follow-up of at least 3 months (90d) were included in this study. The best corrected distance visual acuity (BCDVA), the intraocular pressure (IOD), the rate of re-keratoplasty and the rebubbling rate were inter alia recorded. The results of patients with (group 1) and without a preexisting glaucoma (group 2) were compared. 74 eyes of 59 patients with a mean follow-up of 152 ± 70 days were included. 65 eyes were in group 1 and 9 eyes in group 2. The BCDVA significantly improved in both groups after surgery (p glaucoma compared to patients with a preexisting glaucoma. In the early stage outcome of DMEK no significant impact of a preexisting glaucoma was found.

Organ culture storage of pre-prepared corneal donor material for Descemet's membrane endothelial keratoplasty.

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Bhogal, Maninder; Matter, Karl; Balda, Maria S; Allan, Bruce D

2016-11-01

To evaluate the effect of media composition and storage method on pre-prepared Descemet's membrane endothelial keratoplasty (DMEK) grafts. 50 corneas were used. Endothelial wound healing and proliferation in different media were assessed using a standard injury model. DMEK grafts were stored using three methods: peeling with free scroll storage; partial peeling with storage on the stroma and fluid bubble separation with storage on the stroma. Endothelial cell (EC) phenotype and the extent of endothelial overgrowth were examined. Global cell viability was assessed for storage methods that maintained a normal cell phenotype. 1 mm wounds healed within 4 days. Enhanced media did not increase EC proliferation but may have increased EC migration into the wounded area. Grafts that had been trephined showed evidence of EC overgrowth, whereas preservation of a physical barrier in the bubble group prevented this. In grafts stored in enhanced media or reapposed to the stroma after trephination, endothelial migration occurred sooner and cells underwent endothelial-mesenchymal transformation. Ongoing cell loss, with new patterns of cell death, was observed after returning grafts to storage. Grafts stored as free scrolls retained more viable ECs than grafts prepared with the fluid bubble method (74.2± 3% vs 60.3±6%, p=0.04 (n=8). Free scroll storage is superior to liquid bubble and partial peeling techniques. Free scrolls only showed overgrowth of ECs after 4 days in organ culture, indicating a viable time window for the clinical use of pre-prepared DMEK donor material using this method. Methods for tissue preparation and storage media developed for whole corneas should not be used in pre-prepared DMEK grafts without prior evaluation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Quantitative Analysis of Endothelial Cell Loss in Preloaded Descemet Membrane Endothelial Keratoplasty Grafts.

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Wolle, Meraf A; DeMill, David L; Johnson, Lauren; Lentz, Stephen I; Woodward, Maria A; Mian, Shahzad I

2017-11-01

Availability of preloaded Descemet membrane endothelial keratoplasty (pDMEK) tissue may increase acceptance of DMEK in surgical management of endothelial disease. The goal of this study was to determine the safety of pDMEK grafts for 24 hours before surgery by analyzing endothelial cell loss (ECL) using 2 image analysis software programs. A total of 18 cadaveric corneas were prepared for DMEK using a standardized technique and loaded in a modified Jones tube injector. Nine of the corneas were injected into Calcein AM vital dye after 1 minute (controls), and the remaining 9 corneas were left preloaded for 24 hours before injection into vital dye for staining. The stained corneas were imaged using an inverted confocal microscope. ECL was then analyzed and quantified by 2 different graders using 2 image analysis software programs. The control DMEK tissue resulted in 22.0% ± 4.0% ECL compared with pDMEK tissue, which resulted in 19.2% ± 7.2% ECL (P = 0.31). Interobserver agreement was 0.93 for MetaMorph and 0.92 for Fiji. The average time required to process images with MetaMorph was 2 ± 1 minutes and with Fiji was 20 ± 10 minutes. Intraobserver agreement was 0.97 for MetaMorph and 0.93 for Fiji. Preloading DMEK tissue is safe and may provide an alternative technique for tissue distribution and surgery for DMEK. The use of MetaMorph software for quantifying ECL is a novel and accurate imaging method with increased efficiency and reproducibility compared with the previously validated Fiji.

Standardization of the Descemet membrane endothelial keratoplasty technique: Outcomes of the first 450 consecutive cases.

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Satué, M; Rodríguez-Calvo-de-Mora, M; Naveiras, M; Cabrerizo, J; Dapena, I; Melles, G R J

2015-08-01

To evaluate the clinical outcome of the first 450 consecutive cases after Descemet membrane endothelial keratoplasty (DMEK), as well as the effect of standardization of the technique. Comparison between 3 groups: Group I: (cases 1-125), as the extended learning curve; Group II: (cases 126-250), transition to technique standardization; Group III: (cases 251-450), surgery with standardized technique. Best corrected visual acuity, endothelial cell density, pachymetry and intra- and postoperative complications were evaluated before, and 1, 3 and 6 months after DMEK. At 6 months after surgery, 79% of eyes reached a best corrected visual acuity of≥0.8 and 43%≥1.0. Mean preoperative endothelial cell density was 2,530±220 cells/mm2 and 1,613±495 at 6 months after surgery. Mean pachymetry measured 668±92 μm and 526±46 μm pre- and (6 months) postoperatively, respectively. There were no significant differences in best corrected visual acuity, endothelial cell density and pachymetry between the 3 groups (P > .05). Graft detachment presented in 17.3% of the eyes. The detachment rate declined from 24% to 12%, and the rate of secondary surgeries from 9.6% to 3.5%, from group I to III respectively. Visual outcomes and endothelial cell density after DMEK are independent of the technique standardization. However, technique standardization may have contributed to a lower graft detachment rate and a relatively low number of secondary interventions required. As such, DMEK may become the first choice of treatment in corneal endothelial disease. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of 10% SF6 Gas Compared to 100% Air Tamponade in Descemet's Membrane Endothelial Keratoplasty.

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Rickmann, Annekatrin; Szurman, Peter; Jung, Sacha; Boden, Karl Thomas; Wahl, Silke; Haus, Arno; Boden, Katrin; Januschowski, Kai

2018-04-01

To compare the clinical outcomes following Descemet's membrane endothelial keratoplasty (DMEK) with 100% air tamponade versus 10% sulfur hexafluoride (SF 6 ) tamponade. Retrospective analysis of 108 consecutive DMEK cases subdivided by anterior chamber tamponade with 54 eyes receiving 10% SF 6 and 54 eyes receiving 100% air injection. A post-hoc matched analysis revealed no statistically significant differences between the groups. The main outcome measurements were the complication rate, including intra- and postoperative complications and graft detachment rate requiring re-bubbling. Clinical outcome included best-corrected visual acuity (BCVA), endothelial cell count (ECC), and central corneal thickness (CCT) measured 1, 3, and 6 months after DMEK surgery. The graft detachment rate with consecutive re-bubbling was 18.5% in the air group and 22.2% in the SF 6 group (p = 0.2). Remaining small peripheral graft detachments with a clear cornea occurred more often in the 100% air group (air: 22.2%; 12/54, 6/12 inferior compared to SF 6 : 7.4%; 4/54, 2/4 inferior; p = 0.06). The primary graft failure rate was comparable between the two groups. No complete graft detachment occurred. Outcome results for BCVA, ECC, and CCT at all follow-up time points were comparable between the two groups. The clinical outcomes (including re-bubbling rate, primary graft failure rate, and endothelial cell loss) were comparable with 100% air versus 10% SF 6 tamponade, whereas other studies suggest that a higher SF 6 concentration (20%) may result in a lower re-bubbling rate.

Simultaneous versus sequential penetrating keratoplasty and cataract surgery.

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Hayashi, Ken; Hayashi, Hideyuki

2006-10-01

To compare the surgical outcomes of simultaneous penetrating keratoplasty and cataract surgery with those of sequential surgery. Thirty-nine eyes of 39 patients scheduled for simultaneous keratoplasty and cataract surgery and 23 eyes of 23 patients scheduled for sequential keratoplasty and secondary phacoemulsification surgery were recruited. Refractive error, regular and irregular corneal astigmatism determined by Fourier analysis, and endothelial cell loss were studied at 1 week and 3, 6, and 12 months after combined surgery in the simultaneous surgery group or after subsequent phacoemulsification surgery in the sequential surgery group. At 3 and more months after surgery, mean refractive error was significantly greater in the simultaneous surgery group than in the sequential surgery group, although no difference was seen at 1 week. The refractive error at 12 months was within 2 D of that targeted in 15 eyes (39%) in the simultaneous surgery group and within 2 D in 16 eyes (70%) in the sequential surgery group; the incidence was significantly greater in the sequential group (P = 0.0344). The regular and irregular astigmatism was not significantly different between the groups at 3 and more months after surgery. No significant difference was also found in the percentage of endothelial cell loss between the groups. Although corneal astigmatism and endothelial cell loss were not different, refractive error from target refraction was greater after simultaneous keratoplasty and cataract surgery than after sequential surgery, indicating a better outcome after sequential surgery than after simultaneous surgery.

Comparison of graft survival following penetrating keratoplasty and Descemet's stripping endothelial keratoplasty in eyes with a glaucoma drainage device.

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Iverson, Shawn M; Spierer, Oriel; Papachristou, George C; Feuer, William J; Shi, Wei; Greenfield, David S; O'Brien, Terrence P

2018-02-01

To compare corneal graft survival rates after penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSEK) in patients with a glaucoma drainage device (GDD) or medically managed glaucoma. A retrospective chart review was conducted on consecutive patients who underwent primary PK or primary DSEK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and a minimum of 6 months of follow-up. Graft failure was defined as an edematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularization and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan-Meier survival analysis. Patients were divided into four groups: GDD-PK, GDD-DSEK, medical-PK and medical-DSEK. Fifty-six eyes of 56 patients were identified as meeting inclusion criteria. Among eyes with a GDD, there was no difference in the proportion of failures between PK grafts (48%) and DSEK grafts (50%) (p = 0.90). Failure occurred earlier in DSEK recipients compared to PK recipients, 5.82 ± 6.77 months versus 14.40 ± 7.70 months, respectively (p = 0.04). A Kaplan-Meier analysis did not identify a difference between the four groups with respect to graft failure (p = 0.52). There is no significant difference in graft survival rates between medically and surgically treated glaucoma patients for either PK or DSEK grafts. In patients with GDD, graft failure occurs earlier in DSEK compared to PK.

Hybrid Technique of Lamellar Keratoplasty (DMEK-S

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Pavel Studeny

2013-01-01

Full Text Available Purpose: To evaluate the outcomes of the hybrid technique of posterior lamellar keratoplasty (DMEK-S. Materials and Methods: 71 eyes of 55 patients enrolled in a single-center study underwent posterior lamellar keratoplasty with a hybrid lamella DMEK-S implanted using a solution implantation technique, owing to endothelial dysfunction. The outcome measures studied were visual acuity and endothelial cell density. Results: The rate of endothelial cell loss caused by surgery was 43.8%. During followups, we observed the stabilization of postoperative findings, or at minimum a very low rate of corneal endothelial cell loss. The UCDVA and BCDVA dramatically improved postoperatively. The rebubbling rate in our group of patients was 61.9%. We replaced the lamella due to its failure or malfunction in 17 patients (23.9%. Conclusion: In summary, DMEK-S combines the advantages of DSEK/DSAEK and DMEK. The central zone of bare Descemet’s membrane and endothelium allows for very good visual outcomes, and the peripheral rim allows for better manipulation of the lamella during implantation. It is an effective method of treating the endothelial dysfunction of various etiologies, but the high complication rate needs to be addressed before widespread implementation of the technique in the future.

Electrospun nanofibrous SF/P(LLA-CL membrane: a potential substratum for endothelial keratoplasty

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Chen JZ

2015-05-01

Full Text Available Junzhao Chen,1,* Chenxi Yan,1,* Mengyu Zhu,1,* Qinke Yao,1 Chunyi Shao,1 Wenjuan Lu,1 Jing Wang,2 Xiumei Mo,2 Ping Gu,1 Yao Fu,1 Xianqun Fan1 1Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Biomaterials and Tissue Engineering Laboratory, College of Chemistry and Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Cornea transplant technology has progressed markedly in recent decades, allowing surgeons to replace diseased corneal endothelium by a thin lamellar structure. A thin, transparent, biocompatible, tissue-engineered substratum with corneal endothelial cells for endothelial keratoplasty is currently of interest. Electrospinning a nanofibrous structure can simulate the extracellular matrix and have beneficial effects for cell culture. Silk fibroin (SF has good biocompatibility but poor mechanical properties, while poly(L-lactic acid-co-Ɛ-caprolactone (P(LLA-CL has good mechanical properties but poor biocompatibility. Blending SF with P(LLA-CL can maintain the advantages of both these materials and overcome their disadvantages. Blended electrospun nanofibrous membranes may be suitable for regeneration of the corneal endothelium. The aim of this study was to produce a tissue-engineered construct suitable for endothelial keratoplasty.Methods: Five scaffolds containing different SF:P(LLA-CL blended ratios (100:0, 75:25, 50:50, 25:75, 0:100 were manufactured. A human corneal endothelial (B4G12 cell line was cultured on the membranes. Light transmission, speed of cell adherence, cell viability (live-dead test, cell proliferation (Ki-67, BrdU staining, and cell monolayer formation were detected on membranes with the different blended ratios, and expression of some functional genes was also detected by real-time polymerase chain reaction.Results: Different blended ratios of scaffolds

Long-Term Functional and Anatomical Outcome after Descemet Stripping Automated Endothelial Keratoplasty: A Prospective Single-Center Study

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Jeroen van Rooij

2018-01-01

Full Text Available Purpose. To investigate the long-term anatomical and functional outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK. Methods. Prospective follow-up of 114 eyes (95 subjects after DSAEK for endothelial dysfunction. Measurements included best spectacle-corrected visual acuity (BSCVA, straylight, endothelial cell density (ECD, and graft thickness. Results. The mean follow-up time was 5.1 ± 1.5 years. Four grafts ultimately failed (after 5 to 7 years. From baseline up to 1 year after DSAEK, mean BSCVA improved by 0.30 logMAR. This beneficial effect remained until the last follow-up (LFU. After DSAEK, straylight was reduced. ECD sharply dropped by 900 cells/mm2 (33% immediately after surgery and, thereafter, steadily decreased at a rate of 11 cells/mm2 per month. No significant correlation was observed between graft thickness at 3 years and BSCVA. Conclusions. We observed a low graft failure rate and a normalization of graft thickness. Postoperative straylight remained elevated relative to the normal population. The sharp initial and the subsequent more gradual ECD decline are consistent with other studies. A significant and prolonged functional gain can be achieved by posterior lamellar grafting for endothelial dysfunction.

Clinical Validation of Point-Source Corneal Topography in Keratoplasty

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Vrijling, A C L; Braaf, B.; Snellenburg, J.J.; de Lange, F.; Zaal, M.J.W.; van der Heijde, G.L.; Sicam, V.A.D.P.

2011-01-01

Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using

Complications and management in Descemet′s stripping endothelial keratoplasty: Analysis of consecutive 430 cases

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Samar K Basak

2014-01-01

Full Text Available Purpose: To analyze the complications and their managements in Descemet′s stripping endothelial keratoplasty (DSEK in consecutive 430 cases by single surgeon in a tertiary eye hospital. Materials and Methods: 430 eyes of 366 patients with endothelial dysfunctions scheduled for DSEK, were analyzed retrospectively. In all cases donor dissection was performed manually, and ′Taco′ insertion and unfolding technique was used. Intra-operative and postoperative complications with their managements and outcomes were reviewed retrospectively. Periodic endothelial cell density was analyzed for each patient till the last visit. Follow-up period was between 3 to 60 months (mean 18.7 months. Results: 13 (3.0% eyes had operative complications during donor dissection and 16 (3.7% had during recipient procedure. In 7 (1.6% eyes, donor lenticule was replaced with a new one during the surgery. In early postoperative period, 21 (4.9% eyes had donor dislocation and 12 (2.8% eyes had air-induced pupillary block; and they were managed immediately. 2 cases had primary graft failure and in 1 case had postoperative bacterial endophthalmitis requiring evisceration. In late postoperative period, 48 (11.3% eyes had secondary glaucoma and 14 (3.3% eyes had late secondary graft failure. Endothelial rejection occurred in 5 (1.2% cases. Mean endothelial cell loss was 19.7% after 3 months and 54.2% after 5 years. Total graft failure in this series was 31 (7.2% and in 17 cases re-DSEK was performed successfully. Conclusions: Both operative and postoperative complications do occur in DSEK. Most of these complications can be managed by medical or appropriate surgical means. Some of the complications can be avoided and reduced with experience.

Recurrent progressive anterior segment fibrosis syndrome following a descemet-stripping endothelial keratoplasty in an infant with congenital aniridia

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Mihir Kothari

2014-01-01

Full Text Available Progressive anterior segment fibrosis syndrome (ASFS, after intraocular surgery in older children (≥9 years and adults with congenital aniridia, is described in the literature. In this report, we describe an unique case of ASFS in an infant with congenital aniridia following a combined trabeculotomy-ectomy and its recurrence after a descemet stripping endothelial keratoplasty. The ophthalmologists should be well aware of this entity and warn the parents about its possibilities. Use of immunomodulators or prolonged anti-inflammatory therapy may be considered to prevent its occurrence.

Patients with Fuchs Endothelial Dystrophy and Cataract Undergoing Descemet Stripping Automated Endothelial Keratoplasty and Phacoemulsification with Intraocular Lens Implant: Staged versus Combined Procedure Outcomes.

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Sykakis, Evripidis; Lam, Fook Chang; Georgoudis, Panagiotis; Hamada, Samer; Lake, Damian

2015-01-01

Purpose. To compare the surgical outcomes of staged and combined phacoemulsification with intraocular lens implant (phaco+IOL) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with Fuchs' endothelial dystrophy and cataract. Setting. Corneoplastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, UK. Methods. Retrospective study of patients who had combined phaco+IOL and DSAEK (group 1) or phaco+IOL followed within 2 months by DSAEK (group 2). Patients who had previous eye surgery or any other ocular comorbidities were excluded. Results. There were 28 eyes in group 1 and 31 in group 2. There were no significant differences in the demographics and corneal tissue characteristics of the two groups. The endothelial disc dislocation and rebubbling rate within 1 week in group 1 was 21.42% and in group 2 was 3.2% (P = 0.04), while the endothelial cell density at 12 months was 1510 ± 433 for group 1 and 1535 ± 482 for group 2 (P = 0.89). The mean 12-month logMAR visual acuity was 0.28 ± 0.24 for group 1 and 0.33 ± 0.15 for group 2 (P = 0.38). Conclusions. Although the combined procedure seems to be associated with a higher complication rate the final outcomes seem to be similar to both methods.

One-year follow-up of femtosecond laser-assisted penetrating keratoplasty

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Tan JCH

2013-02-01

Full Text Available Johnson Choon-Hwai Tan, Wee-Jin HengNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, SingaporeBackground: The purpose of this report is to describe the initial outcomes of femtosecond laser-assisted penetrating keratoplasty.Methods: This retrospective surgical case series consisted of 10 eyes from 10 patients undergoing penetrating keratoplasty at a tertiary center. Femtosecond laser was used to perform a zig-square incision on the donor cornea with matched dimensions on the recipient cornea. Outcomes measured included: unaided visual acuity and best spectacle-corrected visual acuity preoperatively and at one, 3, 6, and 12 months postoperatively; manifest refractive and topographic astigmatism at 3, 6, and 12 months postoperatively; and endothelial cell density loss, calculated at the end of the one-year follow-up period.Results: At one-year follow-up, there was an improvement in unaided visual acuity from a mean preoperative logMAR of 1.67 to 0.44, and best spectacle-corrected visual acuity from a mean preoperative logMAR of 1.33 to 0.13. By postoperative month 3, mean manifest refractive and topographic astigmatism was 2.31 ± 1.41 D and 2.59 ± 1.57 D, respectively. The mean reduction in endothelial cell density was 20.7% after one year of follow-up.Conclusion: Femtosecond laser-assisted penetrating keratoplasty provided a good visual outcome and early visual rehabilitation due to precise graft-host alignment and reduced astigmatism in the early postoperative months.Keywords: penetrating keratoplasty, femtosecond laser-assisted keratoplasty

Indications of Optical Coherence Tomography in Keratoplasties: Literature Review

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Thiago Trindade Nesi

2012-01-01

Full Text Available Optical coherence tomography (OCT of the anterior segment, in particular corneal OCT, has become a reliable tool for the cornea specialist, as it provides the acquisition of digital images at high resolution with a noncontact technology. In penetrating or lamellar keratoplasties, OCT can be used to assess central corneal thickness and pachymetry maps, as well as precise measurements of deep stromal opacities, thereby guiding the surgeon to choose the best treatment option. OCT has also been used to evaluate the keratoplasty postoperative period, for early identification of possible complications, such as secondary glaucoma or donor disc detachments in endothelial keratoplasties. Intraoperatively, OCT can be used to assess stromal bed regularity and transparency in anterior lamellar surgeries, especially for those techniques in which a bare Descemet’s membrane is the goal. The purpose of this paper is to review and discuss the role of OCT as a diagnostic tool in various types of keratoplasties.

Changes in corneal sensation, epithelial damage, and tear function after descemet stripping automated endothelial keratoplasty.

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Hirayama, Yumiko; Satake, Yoshiyuki; Hirayama, Masatoshi; Shimazaki-Den, Seika; Konomi, Kenji; Shimazaki, Jun

2013-09-01

To study the ocular surface changes in eyes after Descemet stripping automated endothelial keratoplasty (DSAEK) compared with those after penetrating keratoplasty (PKP). This prospective study compared the changes in 31 eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease-matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial integrity was evaluated using a fluorescein staining score. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using the Schirmer test, tear clearance test, tear function index, and tear break-up time. The postoperative fluorescein staining score was significantly higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal sensation was significantly better in the DSAEK group than in the PKP group (P sensation after DSAEK was significantly better than the preoperative value (P = 0.02). There were no statistically significant changes in the Schirmer test, tear clearance test, tear function index, or break-up time before and after the surgery in both the DSAEK and PKP groups. No significant differences were observed between the DSAEK and PKP groups after the surgery. Corneal sensation was preserved, and epithelial damage was less severe after DSAEK compared with PKP. Preservation of corneal sensation may contribute to the early recovery of visual function and long-term maintenance of ocular surface health after DSAEK.

An ?All-laser? Endothelial Transplant

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Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

2015-01-01

The ?all laser? assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in...

Air Versus Sulfur Hexafluoride Gas Tamponade in Descemet Membrane Endothelial Keratoplasty: A Fellow Eye Comparison.

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von Marchtaler, Philipp V; Weller, Julia M; Kruse, Friedrich E; Tourtas, Theofilos

2018-01-01

To perform a fellow eye comparison of outcomes and complications when using air or sulfur hexafluoride (SF6) gas as a tamponade in Descemet membrane endothelial keratoplasty (DMEK). One hundred thirty-six eyes of 68 consecutive patients who underwent uneventful DMEK in both eyes for Fuchs endothelial corneal dystrophy were included in this retrospective study. Inclusion criteria were air tamponade (80% of the anterior chamber volume) in the first eye and 20% SF6 gas tamponade (80% of the anterior chamber volume) in the second eye; and same donor tissue culture condition in both eyes. All eyes received laser iridotomy on the day before DMEK. Main outcome measures included preoperative and postoperative best-corrected visual acuity, endothelial cell density, corneal volume, rebubbling rate, and rate of postoperative pupillary block caused by the air/gas bubble. Thirteen of 68 eyes (19.1%) with an air tamponade needed rebubbling compared with 4 of 68 eyes (5.9%) with an SF6 gas tamponade (P = 0.036). Postoperative pupillary block necessitating partial release of air/gas occurred in 1 eye (1.5%) with an air tamponade and 3 eyes (4.4%) with an SF6 gas tamponade (P = 0.301). There were no significant differences in preoperative and postoperative best-corrected visual acuity, endothelial cell density, and corneal volume within 3-month follow-up. Our results confirm the previously reported better graft adhesion when using an SF6 gas tamponade in DMEK without increased endothelial cell toxicity. The rate of pupillary block in eyes with an SF6 gas tamponade was comparable to that with an air tamponade. As a consequence, we recommend using SF6 gas as the tamponade in DMEK.

Candida Endophthalmitis After Descemet Stripping Automated Endothelial Keratoplasty With Grafts From Both Eyes of a Donor With Possible Systemic Candidiasis.

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Palioura, Sotiria; Sivaraman, Kavitha; Joag, Madhura; Sise, Adam; Batlle, Juan F; Miller, Darlene; Espana, Edgar M; Amescua, Guillermo; Yoo, Sonia H; Galor, Anat; Karp, Carol L

2018-04-01

To report 2 cases with late postoperative Candida albicans interface keratitis and endophthalmitis after Descemet stripping automated endothelial keratoplasty (DSAEK) with corneal grafts originating from a single donor with a history of presumed pulmonary candidiasis. Two patients underwent uncomplicated DSAEK by 2 corneal surgeons at different surgery centers but with tissue from the same donor and were referred to the Bascom Palmer Eye Institute with multifocal infiltrates at the graft-host cornea interface 6 to 8 weeks later, and anterior chamber cultures that were positive for the same genetic strain of C. albicans. Immediate explantation of DSAEK lenticules and daily intracameral and instrastromal voriconazole and amphotericin injections failed to control the infection. Thus, both patients underwent therapeutic penetrating keratoplasty with intraocular lens explantation, pars plana vitrectomy, and serial postoperative intraocular antifungal injection. Both patients are doing well at 2 years postoperatively with best-corrected vision of 20/20 and 20/30+ with rigid gas permeable lenses. One patient required repeat optical penetrating keratoplasty and glaucoma tube implantation 1 year after the original surgery. Literature review reveals that donor lenticule explantation and intraocular antifungals are often inadequate to control fungal interface keratitis, and a therapeutic graft is commonly needed. Interface fungal keratitis and endophthalmitis due to infected donor corneal tissue is difficult to treat, and both recipients of grafts originating from the same donor are at risk of developing this challenging condition.

Descemet Membrane Endothelial Keratoplasty Learning Curve for Graft Preparation in an Eye Bank Using 645 Donor Corneas.

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Parekh, Mohit; Ruzza, Alessandro; Romano, Vito; Favaro, Elisa; Baruzzo, Mattia; Salvalaio, Gianni; Grassetto, Andrea; Ferrari, Stefano; Ponzin, Diego

2018-03-01

To investigate the learning curve of Descemet membrane endothelial keratoplasty (DMEK) graft preparation in an eye bank. Four operators prepared 645 DMEK grafts using the stripping technique between 2014 and 2017 at the Veneto Eye Bank Foundation, Italy. Endothelial cell loss (ECL) and tissue wastage were recorded retrospectively after DMEK preparation and correlated with the number of tissues prepared each year by each operator. On average, our operators performed 1 donor preparation a week over the course of this study. Only donors older than 60 years were used in this study, and approximately 10% of donors had diabetes. The Wilcoxon test for paired data and 1-way ANOVA were used for checking statistical significance with the Tukey test as post hoc analysis. P 0.05). There is a learning curve for DMEK graft preparation. ECL and tissue wastage can be reduced with practice and skills. However, each operator may be limited to his or her own learning capability.

Clinical outcomes of trabeculectomy vs. Ahmed glaucoma valve implantation in patients with penetrating keratoplasty : (Trabeculectomy vs. Ahmed galucoma valve in patients with penetrating keratoplasty).

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Akdemir, Mehmet Orcun; Acar, Banu Torun; Kokturk, Furuzan; Acar, Suphi

2016-08-01

The aim of this study was to compare the visual outcomes, intraocular pressure (IOP), and endothelial cell loss caused by trabeculectomy (TRAB) and Ahmed glaucoma valve (AGV) implantation in patients who had previously undergone penetrating keratoplasty (PKP). The data from all patients who underwent surgical treatment of glaucoma after PKP were reviewed at the Cornea Department of Haydarpasa Numune Education and Research Hospital. Eighteen patients who had undergone surgical treatment of glaucoma after PKP were included in this retrospective study. Time between PKP and glaucoma surgeries, visual acuity results, IOP results, endothelial cell counts (ECC) before the surgery, at 1st, 6th, and 12th month of surgery were recorded. Differences between two groups were evaluated. Mean loss of ECC was 315 cells/mm(2) in the AGV group and 197 cells/mm(2) in TRAB group at 12th month of glaucoma surgery. The difference between endothelial cell loss at 12th month of surgery was statistically significant and higher in AGV group (p glaucoma. Ahmed glaucoma valve had a significantly better IOP lowering but higher endothelial cell loss effect.

Patients with Fuchs Endothelial Dystrophy and Cataract Undergoing Descemet Stripping Automated Endothelial Keratoplasty and Phacoemulsification with Intraocular Lens Implant: Staged versus Combined Procedure Outcomes

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Evripidis Sykakis

2015-01-01

Full Text Available Purpose. To compare the surgical outcomes of staged and combined phacoemulsification with intraocular lens implant (phaco+IOL and Descemet stripping automated endothelial keratoplasty (DSAEK in patients with Fuchs’ endothelial dystrophy and cataract. Setting. Corneoplastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, UK. Methods. Retrospective study of patients who had combined phaco+IOL and DSAEK (group 1 or phaco+IOL followed within 2 months by DSAEK (group 2. Patients who had previous eye surgery or any other ocular comorbidities were excluded. Results. There were 28 eyes in group 1 and 31 in group 2. There were no significant differences in the demographics and corneal tissue characteristics of the two groups. The endothelial disc dislocation and rebubbling rate within 1 week in group 1 was 21.42% and in group 2 was 3.2% P=0.04, while the endothelial cell density at 12 months was 1510±433 for group 1 and 1535±482 for group 2 P=0.89. The mean 12-month logMAR visual acuity was 0.28±0.24 for group 1 and 0.33±0.15 for group 2 P=0.38. Conclusions. Although the combined procedure seems to be associated with a higher complication rate the final outcomes seem to be similar to both methods.

Ceratoplastia endotelial lamelar profunda em distrofia de Fuchs: relato de caso Deep lamellar endothelial keratoplasty in Fuchs' dystrophy: case report

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Fernando Trench de Oliveira Komatsu

2004-08-01

Full Text Available Descrever o caso de paciente portador de distrofia de Fuchs submetido a ceratoplastia endotelial lamelar profunda. O procedimento cirúrgico foi realizado no olho direito em um caso de distrofia de Fuchs com falência endotelial. Realizou-se incisão límbica superior, o estroma corneano foi delaminado e um disco lamelar de 8,5 mm com 0,150 mm de espessura, contendo estroma, membrana de Descemet e endotélio, foi transplantado sem sutura corneana. Foram avaliados: acuidade visual sem e com correção, biomicroscopia, topografia, paquimetria ultra-sônica e densidade endotelial. A paciente apresentava na avaliação pré-operatória acuidade visual com correção de 20/100 (+4,00 DE -3,25 DC x 60º, astigmatismo de 6,6 dioptrias (37,5 a 12º x 44,1 a 102º, espessura paquimétrica de 0,625 mm e contagem endotelial de 720 cel/mm². Após três meses da cirurgia, apresentava-se com acuidade visual com correção de 20/30 (-1,25 DE -0,50 DC x 45º, astigmatismo regular de 1,0 dioptria (37,2 a 75º x 38,2 a 165º, espessura paquimétrica de 0,503 mm e contagem endotelial de 2447 cel/mm². Observaram-se como complicações: corte inadvertido da íris, má coaptação de bordas, dobras do disco doador e nébula na interface. Os resultados preliminares sugerem que a ceratoplastia endotelial lamelar posterior é uma alternativa para o tratamento cirúrgico da distrofia de Fuchs com falência endotelial. Seguimento mais prolongado e maior número de casos são necessários para melhor entendimento e caracterização desta técnica e de suas repercussões.To report a case of deep lamellar endothelial keratoplasty (DLEK technique applied to a patient with Fuchs' dystrophy. The surgical procedure was performed on the right eye for a case of Fuchs' dystrophy with endothelial failure. Through a 9 mm self-sealing scleral tunnel incision, a stromal pocket was dissected at 0.35 mm depth. A 8.5 mm lamellar donor disc with 0.150 mm thickness, containing posterior

New continuous air pumping technique to improve clinical outcomes of descemet-stripping automated endothelial keratoplasty in asian patients with previous ahmed glaucoma valve implantation.

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Chang-Min Liang

Full Text Available BACKGROUND: To evaluate the outcomes of Descemet-stripping automated endothelial keratoplasty (DSAEK with the use of continuous air pumping technique in Asian eyes with previous Ahmed glaucoma valve implantation. METHODS: The DSAEK procedure was modified in that complete air retention of the anterior chamber was maintained for 10 min using continuous air pumping at 30 mm Hg. The primary outcome measurement was graft survival, and postoperative clinical features including, rate of graft detachment, endothelial cell count, intraocular pressure (IOP, surgical time and cup/disc ratio were also recorded. RESULTS: A total of 13 eyes of 13 patients which underwent modified DSAEK and 6 eyes of 6 patients which underwent conventional DSAEK were included. There was a significant difference in graft survival curves between two groups (P = 0.029; the 1-year graft survival rates were estimated as 100% and 66.7% for patients with modified DSAEK and those with traditional DSAEK, respectively. The rate of graft detachment were 0% and 33.3% for the modified DSAEK and conventional DSAEK groups, respectively (P = 0.088. The significantly lowered surgical time for air tamponade was noted in the modified DSAEK group compared to that in the conventional DSAEK group [median (IQR: 10.0 (10.0, 10.0 min vs. 24.5 (22.0, 27.0 min; P<0.001] Postoperatively, patients in the modified DSAEK group had significantly lower IOP as compared to the conventional DSAEK group [12.0 (11.0, 15.0 mm Hg vs. 16.0 (15.0, 18.0 mm Hg; P = 0.047]. Modified DSAEK patients had higher endothelial cell counts as compared to conventional DSAEK patients [2148.0 (1964.0, 2218.0 vs. 1529.0 (713.0, 2014.0], but the difference did not reach statistical significance (P = 0.072. CONCLUSIONS: New continuous air pumping technique in DSAEK can be performed safely and effectively in patients with prior GDDs placement who have corneal failure.

Descemet's stripping-automated endothelial keratoplasty for symptomatic thioridazine deposits in the cornea

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Masoumeh Mohebbi

2017-01-01

Full Text Available The aim of this study was to use Descemet's Stripping-automated Endothelial Keratoplasty (DSAEK as a novel treatment to remove thioridazine corneal deposits. A 53-year-old female presented with a 3-month history of visual loss and glare. She had been taking thioridazine (100 mg/day for 1 year for a psychiatric disorder. Dense yellowish-brown deposits had developed in the posterior stroma. Thioridazine was discontinued, and she was switched to fluoxetine. One year after discontinuation of thioridazine, her symptoms and signs did not resolve. Standard DSAEK was performed on her left eye. Two weeks after DSAEK, an anterior subcapsular cataract was detected in the same eye. Phacoemulsification and intraocular lens implantation were performed after 3 months. The left cornea became completely clear after DSAEK, and the patient's best-corrected visual acuity improved from 20/40 to 20/20 at 1 month after cataract surgery. All-visual symptoms such as glare and halos improved postoperatively. We suggest that DSAEK can be used as a novel treatment to reduce vision problems caused by thioridazine-induced corneal deposits.

CLINICAL OUTCOME OF PENETRATING KERATOPLASTY IN CORNEAL OPACITIES OF DIFFERENT AETIOLOGY- A CLINICAL STUDY

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Dipak Bhuyan

2017-01-01

Full Text Available BACKGROUND Corneal transplantation or grafting is an operation in which abnormal corneal host tissue is replaced by healthy donor cornea. According to the World Health Organization (WHO, corneal diseases are among the major causes of vision loss and blindness in the world today after cataract and glaucoma. The aim of the study is to- 1. Evaluate the different aetiology of corneal opacity including active infective aetiology as indicated for penetrating keratoplasty. 2. Determine the clinical outcome of penetrating keratoplasty in relation to graft survival, graft rejection and peri-operative complications in different aetiology groups. 3. Determine the final visual outcome. MATERIALS AND METHODS Candidates for keratoplasty were selected from- 1. Eye Bank of Regional Institute of Ophthalmology (R.I.O. 2. R.I.O OPD. The study period was from September 2014 to August 2015. 30 cases were taken in the study. Descriptive statistics were applied to analyse the data wherever necessary. RESULTS 34.6±19.73 yrs. (mean±SD was the mean age at which transplants were done in the study. Out of total 30 cases, 13 (43.33% and 17 (56.66% were male and female, respectively. The different indications for penetrating keratoplasty are- Post ulcer corneal opacity in 14 cases (46.66%, posttraumatic corneal opacity 9 cases (30%, pseudophakic bullous keratopathy 4 cases (13.33%, corneal dystrophy in 2 cases (6.66% and non-healing corneal ulcer in 1 case (3.33%. 16 cases (53.33% showed clear graft till the last follow up while 11 (33.33% cases showed partially clear graft resulting in improved visual outcome while 3 cases (10.00% of the grafts were opaque due to graft failure. CONCLUSION The major indications for penetrating keratoplasty in this part of the world are post ulcer and posttraumatic corneal opacity and majority of them are illiterate agricultural workers who failed to get adequate treatment on time. Graft survival rate is high, which can be attributed to the

Precut cornea for Descemet's stripping endothelial keratoplasty: experience at a single eye bank.

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Mohamed, Ashik; Chaurasia, Sunita; Chandragiri, Venkataswamy; Kandhibanda, Srinivas; Gunnam, Srinivas; Garg, Prashant

2017-06-01

The aim of the study is to describe the experience with precut facility for endothelial keratoplasty at a single eye bank affiliated to a tertiary eye care center in India. Data on precut tissues from Nov 2012 to Dec 2014 were retrospectively reviewed from the electronic database of the eye bank of a tertiary eye care center in South India. Donor characteristic data including donor age, precut and postcut endothelial cell density (ECD), recipient age, and thickness of graft were collected. The number of precuts increased from 42 in 2012 (Nov and Dec) and 422 in 2013 to 584 in 2014. Of the total of 1048 precuts, seven (0.67 %) were miscut and could not be utilized for transplants. The donor age ranged from 2 to 89 years. A mean change of 43.6 ± 325.2 cells/mm 2 in ECD was noted after cut, proportional increase in mean being 1.9 %. The change in ECD after cut was negatively correlated with ECD before cut. The recipient age ranged from 1 to 89 years. The median thickness of donor lenticule after cut was 148 µm (interquartile range 131-166 µm). Analysis of precut donor corneas from a single eye bank shows that the ECD of the processed tissues was excellent for transplantation. The tissue wastage in the hands of eye bank personal was minimal.

Nomogram to Predict Graft Thickness in Descemet Stripping Automated Endothelial Keratoplasty: An Eye Bank Study.

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Bae, Steven S; Menninga, Isaac; Hoshino, Richard; Humphreys, Christine; Chan, Clara C

2018-06-01

The purpose of this study was to develop a nomogram to predict postcut thickness of corneal grafts prepared at an eye bank for Descemet stripping automated endothelial keratoplasty (DSAEK). Retrospective chart review was performed of DSAEK graft preparations by 3 experienced technicians from April 2012 to May 2017 at the Eye Bank of Canada-Ontario Division. Variables collected included the following: donor demographics, death-to-preservation time, death-to-processing time, precut tissue thickness, postcut tissue thickness, microkeratome head size, endothelial cell count, cut technician, and rate of perforation. Linear regression models were generated for each microkeratome head size (300 and 350 μm). A total of 780 grafts were processed during the study period. Twelve preparation attempts resulted in perforation (1.5%) and were excluded. Mean precut tissue thickness was 510 ± 49 μm (range: 363-670 μm). Mean postcut tissue thickness was 114 ± 22 μm (range: 57-193 μm). Seventy-nine percent (608/768) of grafts were ≤130 μm. The linear regression models included precut thickness and donor age, which were able to predict the thickness to within 25 μm 80% of the time. We report a nomogram to predict thickness of DSAEK corneal grafts prepared in an eye bank setting, which was accurate to within 25 μm 80% of the time. Other eye banks could consider performing similar analyses.

Graft failure: III. Glaucoma escalation after penetrating keratoplasty.

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Greenlee, Emily C; Kwon, Young H

2008-06-01

Glaucoma after penetrating keratoplasty is a frequently observed post-operative complication and is a risk factor for graft failure. Penetrating keratoplasty performed for aphakic and pseudophakic bullous keratopathy and inflammatory conditions are more likely to cause postoperative glaucoma compared with keratoconus and Fuchs' endothelial dystrophy. The intraocular pressure elevation may occur immediately after surgery or in the early to late postoperative period. Early postoperative causes of glaucoma include pre-existing glaucoma, retained viscoelastic, hyphema, inflammation, pupillary block, aqueous misdirection, or suprachoroidal hemorrhage. Late causes include pre-existing glaucoma, angle-closure glaucoma, ghost cell glaucoma, suprachoroidal hemorrhage, and steroid-induced glaucoma. Determining the cause of IOP elevation can help guide therapeutic intervention. Treatments for refractory glaucoma include topical anti-glaucoma medications such as beta-adrenergic blockers. Topical carbonic anhydrase inhibitors, miotic agents, adrenergic agonists, and prostaglandin analogs should be used with caution in the post-keratoplasty patient, because of the possibility of corneal decompensation, cystoid macular edema, or persistent inflammation. Various glaucoma surgical treatments have reported success in post-keratoplasty glaucoma. Trabeculectomy with mitomycin C can be successful in controlling IOP without the corneal toxicity noted with 5-fluorouracil. Glaucoma drainage devices have successfully controlled intraocular pressure in postkeratoplasty glaucoma; this is, however, associated with increased risk of graft failure. Placement of the tube through the pars plana may improve graft success compared with implantation within the anterior chamber. In addition, cyclophotocoagulation remains a useful procedure for eyes that have refractory glaucoma despite multiple surgical interventions.

Comparison of Sulfur Hexafluoride (SF6) and Air Tamponade in Noniridectomized Descemet Membrane Endothelial Keratoplasty.

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Einan-Lifshitz, Adi; Sorkin, Nir; Boutin, Tanguy; Showail, Mahmood; Borovik, Armand; Jamshidi, Farzad; Chan, Clara C; Rootman, David S

2018-03-01

To compare the efficacy and safety of 20% sulfur hexafluoride gas (SF6) and air tamponade in patients who underwent noniridectomized Descemet membrane endothelial keratoplasty (DMEK). A retrospective chart review of patients who underwent DMEK with either air or SF6 tamponade: 41 eyes received air tamponade (group 1) and 41 received SF6 tamponade (group 2). Best spectacle-corrected visual acuity, endothelial cell density, and complications including graft detachment and elevated intraocular pressure were compared. The mean follow-up time was 8 ± 4 months in group 1 and 3 ± 2 months in group 2. Mean best spectacle-corrected visual acuity improved from 1.12 ± 0.88 to 0.64 ± 0.78 logarithm of the minimum angle of resolution (logMAR) in group 1 (P = 0.009) and from 1.00 ± 0.78 to 0.62 ± 0.53 logMAR in group 2 (P = 0.006). The graft detachment rate was 39% (16 eyes) in group 1 and 42% (17 eyes) in group 2 (P = 0.822). The rate of graft detachment larger than one third of the graft area was 17% in group 1 and 20% in group 2 (P = 0.775). Rebubbling was performed in 26.8% and 20% of eyes in group 1 and 2, respectively (P = 0.43). Average endothelial cell loss was 32% in group 1 and 33% in group 2 (P = 0.83). In the immediate postoperative period, elevated intraocular pressure was observed in 2 eyes (5%) in group 1 and in 4 eyes (10%) in group 2 (P = 0.4). There was 1 primary graft failure in each group. Use of air with it being readily available and short acting is a good method of Descemet membrane tamponade in noniridectomized DMEK.

Rebubbling in Descemet Membrane Endothelial Keratoplasty: Influence of Pressure and Duration of the Intracameral Air Tamponade.

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Pilger, Daniel; Wilkemeyer, Ina; Schroeter, Jan; Maier, Anna-Karina B; Torun, Necip

2017-06-01

To explore the impact of intracameral air tamponade pressure and duration on graft attachment and rebubbling rates. A prospective, interventional, nonrandomized study. setting: Department of Ophthalmology, Charité - Universitätsmedizin Berlin. One hundred seventeen patients who underwent Descemet membrane endothelial keratoplasty (DMEK). Intraocular pressure (IOP) at the end of the surgery, immediately after filling the anterior chamber with air, categorized into low (20 mm Hg), and the time until partial removal of the air. Rebubbling rates and endothelial cell density over a 3-month follow-up period analyzed by a multivariable Cox regression model and an analysis of covariance model. Thirty-two patients required a rebubbling (27% [95% CI 19%-35%]). Nine patients required more than 1 rebubbling (7% [95% CI 3%-12%]). Compared with normal IOP, lower (HR 8.98 [95% CI 1.07-75.41]) and higher IOP (HR 10.63 [95% CI 1.44-78.27]) increased the risk of requiring a rebubbling (P = .006). Independent of the IOP, an air tamponade duration beyond 2 hours reduced the risk of rebubbling (HR 0.36 [95% CI 0.18-0.71, P = .003]). One month after surgery, the mean endothelial cell loss was 13% (95% CI 2%-25%) and 23% (95% CI 17%-29%) in the group with air tamponade duration of below and above 2 hours, respectively (P = .126). At 3 months after surgery, it was 31% (95% CI 17%-42%) and 42% (95% CI 32%-52%) in the respective groups (P = .229). A postsurgical air tamponade of at least 2 hours with an IOP within the physiological range could help to reduce rebubbling rates. Copyright © 2017 Elsevier Inc. All rights reserved.

New techniques in lamellar keratoplasty.

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Alio, Jorge L; Shah, Sunil; Barraquer, Carmen; Bilgihan, Kamil; Anwar, Mohammed; Melles, Gerrit R J

2002-08-01

In the past years, several lamellar keratoplasty surgical techniques have been developed, modified or improved in the past years, including microkeratome assisted anterior and posterior lamellar keratoplasty, anterior lamellar keratoplasty using air-dissection or visco-dissection, sutureless posterior lamellar keratoplasty, LASIK for postkeratoplasty astigmatism, and excimer laser assisted keratophakia for keratoconus or to manage complications after LASIK. These procedures may continue to gain interest as alternative procedures for a penetrating keratoplasty in the treatment of various corneal disorders.

Corneal endothelial rejection after penetrating keratoplasty treated with intravenous and topic corticosteroid: one year follow up

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Ricardo Yuji Abe

2013-02-01

Full Text Available OBJECTIVE: To analyze the recovery of visual acuity (VA and graft survival after first episode of endothelial rejection in penetrating keratoplasty (PKP treated with intravenous (IV and topic corticosteroid. METHODS: Interventional, prospective, non-comparative case series study evolving 32 PKP patients in one year follow up, who presented first episode of corneal endothelial rejection. The patients were submitted to 500 mg IV injection of methylprednisolone in association with topical prednisolone. Main outcome measures included VA recovery and corneal edema regression. Second outcome included new rejections and graft failure. Multivariate analysis techniques were used to estimate rates of graft outcome events and the impact of risk factors. RESULTS: A total of 32 eyes from 32 patients (13 male and 19 female were included in the study. The mean VA (in number of letters before rejection was 48 (22 to 88 letters. Patients treated within 7 days or less of initial symptoms had better VA recovery, corneal edema regression and less graft failure (p<0.001. Patients with previous ocular surgery had worse VA recovery and more graft failure (p<0.047. CONCLUSION: The association between the other risk factors and the outcomes did not reach statistical significance in the multivariate model because of the small numbers of patients. Methylprednisolone in association with topical prednisolone is an alternative treatment for graft rejection. Our study showed that patients treated within 7 days of symptoms and no previous anterior segment surgery had better visual outcome and graft survival after treatment.

Corneal iron ring after conductive keratoplasty.

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Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Pallikaris, Ioannis G

2003-08-01

To report formation of corneal iron ring deposits after conductive keratoplasty. Observational case report. Case report. A 54-year-old woman underwent conductive keratoplasty for hyperopia. One year after conductive keratoplasty, iron ring pattern pigmentation was detected at the corneal epithelium of both eyes. This is the first report of the appearance of corneal iron ring deposits following conductive keratoplasty treatment in a patient. It is suggested that alterations in tear film stability, resulting from conductive keratoplasty-induced changes in corneal curvature, constitute the contributory factor for these deposits.

Endophthalmitis after descemet stripping endothelial keratoplasty with concave-oriented dislocation on slit-lamp optical coherence topography.

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Kaiura, Terry L; Ritterband, David C; Koplin, Richard S; Shih, Carolyn; Palmierto, Pat M; Seedor, John A

2010-02-01

To present the first reported case of Descemet membrane stripping endothelial keratoplasty (DSEK)-associated endophthalmitis with concave dislocation on slit-lamp optical coherence topography (SL-OCT). An 86-year-old man underwent DSEK for corneal decompensation secondary to prior surgery. On all postoperative visits, a slit-lamp examination and SL-OCT were performed. On the first postoperative day, the lenticle was dislocated in a concave configuration as imaged with the SL-OCT. On the second postoperative day, the patient had eye pain, nausea, and increased intraocular pressure. On SL-OCT imaging, the concave configuration and fibrin stranding were imaged. With intraocular pressure lowering, the patient's pain subsided, and he was scheduled for a lenticle refloat the following day. The next day, endophthalmitis was diagnosed secondary to exuberant purulent inflammation. At surgery, the lenticle was removed, cultures were obtained, and pars plana vitrectomy and intravitreal injections were administered. Intraoperative cultures were positive for heavy growth of Streptococcus pneumoniae. Endophthalmitis is a potential complication for any intraocular procedure including DSEK. SL-OCT imaging postoperatively may reveal concave lenticle configuration and subtle anterior chamber fibrin stranding may be early sign of endophthalmitis.

Outcome of Descemet stripping automated endothelial keratoplasty in eyes with an Ahmed glaucoma valve.

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Chiam, Patrick J; Cheeseman, Robert; Ho, Vivian W; Romano, Vito; Choudhary, Anshoo; Batterbury, Mark; Kaye, Stephen B; Willoughby, Colin E

2017-05-01

The purpose was to investigate the survival of Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with an Ahmed glaucoma valve (AGV). The study had a retrospective case-series of patients with an AGV in the anterior chamber undergoing a DSAEK. Included in the analysis were graft size, number of previous operations, post-operative glaucoma medications, post-operative intraocular pressure (IOP) control, graft size and donor factors (age, endothelial cell density, and post-mortem time). A generalised linear model with binary logistic regression was used to test for an effect on graft survival at 1 year and 1.5 years. Fourteen eyes from 13 patients were included. The survival rate of the first DSAEK at 6, 12, 18, 24 and 30-months was 85%, 71%, 50%, 36% and 30%, respectively. The mean duration to graft failure was 12.9 ± 6.2 months. Five of the seven failed first grafts went on to have a repeat DSAEK. The mean follow-up in this subgroup was 30.7 ± 18.4 months. The survival rate of second DSAEK at 6, 12, 18 and 24 months was 100% (5/5), 100% (5/5), 75% (3/4) and 67% (2/3). Only one second DSAEK failed in the duration of the study and went on to receive a third DSAEK which failed at 18-months. The mean IOP within the first year was significantly lower for grafts that survived at 1 and 1.5 years (17.4 mmHg, 16.9 mmHg) than for grafts that failed (19.4 mmHg, 19.4 mmHg) (p = 0.04, p = 0.009). DSAEK is a viable alternative to PK to restore visual function in eyes with an AGV sited in the anterior chamber. IOP is an important risk factor for graft failure.

[Remote results of high myopia surgical correction by tunnel keratoplasty ].

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Dushin, N V; Beliaev, V S; Gonchar, P A; Barashkov, V I; Kravchinina, V V; Frolov, M A

2000-01-01

Remote results evidence high refraction efficiency of tunnel keratoplasty, stable results being observed for up to 15 years. A total of 104 operations (58 patients) were analyzed for a period of observation of more than 10 years. The patients' ages varied from 17 to 52 years, there were 34 women and 24 men. The main advantage of interlamellar refraction meridional keratoplasty is easiness of operation. At present it is the operation of choice for dosed reduction of eye refraction aimed at correction of high myopia and astigmatism. The possibility of correcting residual myopia after keratotomy and repair of refraction abnormalities resultant from perforating keratoplasty is particularly interesting. The possibility of regulating the corrective effect in remote periods by replacing the implants also deserves attention. Hence, low traumatism, high efficiency, and stability of the refraction effect once more confirm our recommendation to use tunnel keratoplasty in clinical practice.

Air Pump-Assisted Graft Centration, Graft Edge Unfolding, and Graft Uncreasing in Young Donor Graft Pre-Descemet Endothelial Keratoplasty.

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Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Agarwal, Athiya; A I, Saijimol

2017-08-01

To assess an air pump-assisted technique for graft centration, graft edge unfolding, and graft uncreasing while performing pre-Descemet endothelial keratoplasty (PDEK) using young donor grafts. Continuous pressurized air infusion was used for graft centration, graft edge unfolding, and graft unwrinkling. Ten eyes of 10 patients underwent PDEK with donors aged below 40 years. In all eyes, the donor scrolled into tight scrolls. In all cases, the air pump-assisted technique was effective in positioning and centering the graft accurately and in straightening infolded graft edges and smoothing out graft creases and wrinkles. Endothelial cell loss was 38.6%. Postoperative best-corrected visual acuity at 6 months was 0.66 ± 0.25 in decimal equivalent. Continuous pressurized air infusion acted as a third hand providing a continuous pressure head that supported the graft and prevented graft dislocation as well as anterior chamber collapse during intraocular maneuvering. Adequate maneuvering space was available in all cases, and bleeding, if any, was tamponaded successfully in all cases. Although very young donor grafts may be used for PDEK, they are difficult to center and unroll completely before floating against host stroma. An air pump-assisted technique using continuous pressurized air infusion allows successful final graft positioning even with very young donor corneas. It thus makes surgery easier as several key steps are made easier to handle. It additionally helps in tamponading hemorrhage during peripheral iridectomy, increasing surgical space, preventing fluctuations in the anterior chamber depth, and promoting graft adherence.

Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

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Li Cui

2014-06-01

Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty.

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Zafar, Andleeb; Aslanides, Ioannis M; Selimis, Vasileios; Tsoulnaras, Konstantinos I; Tabibian, David; Kymionis, George D

2018-01-01

We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

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Bernadette K. Madathil

2014-01-01

Full Text Available Endothelial keratoplasty is a recent shift in the surgical treatment of corneal endothelial dystrophies, where the dysfunctional endothelium is replaced whilst retaining the unaffected corneal layers. To overcome the limitation of donor corneal shortage, alternative use of tissue engineered constructs is being researched. Tissue constructs with intact extracellular matrix are generated using stimuli responsive polymers. In this study we evaluated the feasibility of using the thermoresponsive poly(N-isopropylacrylamide-co-glycidylmethacrylate polymer as a culture surface to harvest viable corneal endothelial cell sheets. Incubation below the lower critical solution temperature of the polymer allowed the detachment of the intact endothelial cell sheet. Phase contrast and scanning electron microscopy revealed the intact architecture, cobble stone morphology, and cell-to-cell contact in the retrieved cell sheet. Strong extracellular matrix deposition was also observed. The RT-PCR analysis confirmed functionally active endothelial cells in the cell sheet as evidenced by the positive expression of aquaporin 1, collagen IV, Na+-K+ ATPase, and FLK-1. Na+-K+ ATPase protein expression was also visualized by immunofluorescence staining. These results suggest that the in-house developed thermoresponsive culture dish is a suitable substrate for the generation of intact corneal endothelial cell sheet towards transplantation for endothelial keratoplasty.

Donor cross-linking for keratoplasty: a laboratory evaluation.

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Mukherjee, Achyut; Hayes, Sally; Aslanides, Ioannis; Lanchares, Elena; Meek, Keith M

2015-12-01

This laboratory-based investigation compares the topographic outcomes of conventional penetrating keratoplasty with that of a novel procedure in which donor corneas are cross-linked prior to keratoplasty. Penetrating keratoplasty procedures with continuous running sutures were carried out in a porcine whole globe model. Sixty eyes were randomly paired as 'donor' and 'host' tissue before being assigned to one of two groups. In the cross-linked group, donor corneas underwent riboflavin/UVA cross-linking prior to being trephined and sutured to untreated hosts. In the conventional keratoplasty group, both host and donor corneas remained untreated prior to keratoplasty. Topographic and corneal wavefront measurements were performed following surgery, and technical aspects of the procedure evaluated. Mean keratometric astigmatism was significantly lower in the cross-linked donor group at 3.67D (SD 1.8 D), vs. 8.43 D (SD 2.4 D) in the conventional keratoplasty group (p < 0.005). Mean wavefront astigmatism was also significantly reduced in the cross-linked donor group 4.71 D (SD 2.1) vs. 8.29D (SD 3.6) in the conventional keratoplasty group (p < 0.005). Mean RMS higher order aberration was significantly lower in the cross-linked donor group at 1.79 um (SD 0.98), vs. 3.05 um (SD 1.9) in the conventional keratoplasty group (P = 0.02). Qualitative analysis revealed less tissue distortion at the graft-host junction in the cross-linked group. Cross-linking of donor corneas prior to keratoplasty reduces intraoperative induced astigmatism and aberrations in an animal model. Further studies are indicated to evaluate the implications of this potential modification of keratoplasty surgery.

Graft rejection episodes after Descemet stripping with endothelial keratoplasty: part two: the statistical analysis of probability and risk factors.

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Price, M O; Jordan, C S; Moore, G; Price, F W

2009-03-01

To investigate risk factors and probability of initial immunological graft rejection episodes after Descemet stripping with endothelial keratoplasty (DSEK). Outcomes of 598 DSEK cases from a single tertiary referral centre were reviewed. Risk factors and probability of rejection were assessed by multivariate Cox proportional hazards modelling. Rejection episodes occurred in 54 eyes of 48 patients. Estimated probability of a rejection episode was 7.6% by 1 year and 12% by 2 years after grafting. Relative risk of rejection was five times higher for African-American patients compared with Caucasians (p = 0.0002). Eyes with pre-existing glaucoma (9%) or steroid-responsive ocular hypertension (27%) had twice the relative risk of rejection (p = 0.045) compared with eyes that did not have those problems. Patient age, sex and corneal diagnosis did not significantly influence rejection risk. Risk of rejection was not increased when fellow eyes were grafted within 1 year of the first eye (p = 0.62). Pre-existing glaucoma or steroid-responsive ocular hypertension and race were the two factors that independently influenced relative risk of rejection after DSEK. Rejection risk was not increased if the fellow eye was grafted within the prior year with DSEK.

Outcome of therapeutic penetrating keratoplasty in a tertiary eye care center in Nepal

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Bajracharya L

2015-12-01

Full Text Available Leena Bajracharya, Reeta Gurung Department of Cornea, Tilganga Institute of Ophthalmology, Kathmandu, Nepal Background: Corneal ulcer is an important cause of blindness in developing countries. Therapeutic keratoplasty for infective keratitis is a frequently performed surgery in these countries.Objective: To find out the outcome of therapeutic keratoplasty for infective keratitis.Methods: Records of 5 years were reviewed of patients who underwent therapeutic keratoplasty from 2006 to 2010. Data collected included demographic parameters, indications for surgery, microbiology of the ulcers, type of surgery performed, and donor tissue details. In the follow-up period, ocular status was evaluated in terms of eradication of disease, anatomic success, graft clarity, visual acuity, and development of glaucoma and cataract.Results: In all, 180 eyes of 180 patients were enrolled in the study; 59.4% of the patients were male. Average age was 44.4±16.7 years. Overall, 71% of infective keratitis was perforated. A total of 101 (56% eyes were positive for organisms of which 49 showed pure fungus and 49 showed pure bacteria. The commonest fungus and bacteria isolated were Aspergillus and Streptococcus, respectively. Average follow-up period was 29±23 months. Overall cure rate of infection was 88.8%, anatomical success rate was 89.5%, and graft clarity was 37.2%. Overall, 43.4% had secondary glaucoma. In the postoperative course, 65.8% of phakic eyes had developed cataract. In all, 38.6% of graft had endothelial failure and 24% of the graft failed due to late infective keratitis. Overall functional success with a visual acuity above 6/60 was 25.4%. Bacterial keratitis had a significantly higher cure rate, anatomical success, and graft clarity compared to fungal keratitis.Conclusion: Therapeutic keratoplasty is an important procedure to save the eye and preserve vision in severe infective keratitis. There is a high incidence of postoperative glaucoma

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty

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Andleeb Zafar

2018-02-01

Full Text Available Purpose: We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. Methods: The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK, and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Results: Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. Conclusion: A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

An "All-laser" Endothelial Transplant.

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Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

2015-07-06

The "all laser" assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in the surgery room with optical coherence tomography (OCT), in order to correctly design the donor tissue dimensions. A femtosecond laser is used to cut the donor cornea. The recipient eye is prepared by manual stripping of the descemetic membrane. The donor endothelium is inserted into a Busin-injector, the peripheral inner side is stained with a proper chromophore (a water solution of Indocyanine Green) and then it is pulled in the anterior chamber. The transplanted tissue is placed in the final and correct location and then diode laser welding is induced from outside the eyeball. The procedure has been performed on more than 15 patients evidencing an improvement in surgery performances, with a good recovery of visual acuity and a reduced donor lenticule dislocation event.

Penetrating keratoplasty for treatment of corneal abscesses in horses – case report

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Zita Makra

2013-01-01

Full Text Available This case report describes the surgical technique and outcome of allograft transplantation to treat full thickness corneal abscesses in three horses. In all three cases penetrating keratoplasty was performed. Each affected eye had an abscess within the corneal stroma. An initial full thickness circular corneal incision was made around the lesion. After excision of the stromal abscess the created defect was replaced with a larger diameter full thickness donor graft and the initial corneal incision was repaired. All of the horses that underwent penetrating keratoplasty procedure healed with a scar at the graft site and remained visual. Penetrating keratoplasty is an effective technique for surgical removal of medically nonresponsive full thickness stromal abscess in horses and results in a visual and cosmetically acceptable globe. The advantages of this technique compared to medical therapy are that there is less scarring, shorter healing times and less damage of the globe because of the concurrent uveitis. To the authors’ knowledge, clinical experience with penetrating keratoplasty in horses has not been reported in Europe so far.

Topographic hot spot before descemet stripping automated endothelial keratoplasty is associated with postoperative hyperopic shift.

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Shimizu, Tsutomu; Yamaguchi, Takefumi; Satake, Yoshiyuki; Shimazaki, Jun

2015-03-01

The aim of this study was to investigate topographic "hot spots" on the anterior corneal surface before Descemet stripping automated endothelial keratoplasty (DSAEK) and their effects on postoperative visual acuity and hyperopic shift. Twenty-seven eyes of 27 patients with bullous keratopathy, who underwent DSAEK were studied. We defined a hot spot as a focal area with relatively high refractive power on the anterior corneal surface in eyes with bullous keratopathy. Refractive spherical equivalent, keratometric value, and corneal topography were retrospectively evaluated using anterior segment optical coherence tomography (AS-OCT). Hot spots were identified in 11 eyes (42.3%) before DSAEK and disappeared in 9 eyes of these eyes (81.8%) at 6 months after DSAEK. AS-OCT revealed focal epithelial thickening in the same areas as the hot spots. There was no significant difference in the postoperative visual acuity between eyes with and without hot spots (P > 0.05). The keratometric value of the anterior corneal surface significantly flattened from 45.7 ± 2.7 diopters (D) before DSAEK to 44.2 ± 2.7 D 1 month after DSAEK in eyes with hot spots (P = 0.01), whereas in eyes without hot spots, there were no significant differences in the keratometric values before and after DSAEK. At 6 months, the refractive change was +1.1 ± 1.3 D in eyes with hot spots and -0.2 ± 0.6 D in eyes without hot spots (P = 0.034). In eyes with focal epithelial thickening, topographic hot spots on the anterior corneal surface were observed using AS-OCT. The hot spots disappeared after DSAEK and had no influence on the postoperative visual acuity.

The treatment of acute corneal hydrops by subtotal penetrating keratoplasty. Clinical case

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I. A. Loskutov

2014-07-01

Full Text Available Clinical case of acute hydrops treatment using subtotal penetrating keratoplasty (PK is presented. The diagnosis of acute hydrops was based on clinical and functional evaluations including optical coherent tomography (OCT. A part of diseased cornea was removed and examined under a light microscope. These studies revealed morphological changes in almost all corneal layers. OCT and histology demonstrated that PK was indicated to this patient. Recent literature data on the epidemiology and pathogenesis of acute hydrops are presented. This rare disease results from tears in the Descemet’s membrane that allow aqueous humor to enter the stroma. Current treatment is aimed to suppress corneal inflammation, restore endothelium and Descemet’s membrane integrity and drain stromal cysts to optimize cornea healing. In this case, subtotal PK was performed due to the significant corneal thinning and a high risk of its melting. «Material for corneal graft» (iLab, Moscow, Russia was used as a donor material.

[Posterior lamellar keratoplasty with DSEK technique and use of the Tan EndoGlide - short-term results].

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Kałuiny, Bartłomiej J; Piotrowiak, Ilona; Sołdańska, Beata; Grzybek, Katarzyna; Czajkowska, Monika; Galas, Małgorzata; Malukiewicz, Grazyna

2013-01-01

To present the differences in surgical technique of DSEK (Descemet's Stripping Endothelial Keratoplasty) with the use of Tan EndoGlide (Coronet, UK) and Busin Glide (Moria, FR). Short-term results will also be presented, DSEK was performed in 24 eyes, in 8 cases the surgery was combined with cataract phacoemulsification and lOL implantation. Surgery course and 6 months postoperative results of first 12 eyes performed with the use of Tan EndoGlide were compared with 12 consecutive eyes preformed with Busin Glide. Tan EndoGlide provided much more stable anterior chamber, donor tissue unfolding process was better controlled but the incision was wider incision. Surgically induced mean refractory cylinder 6. months after the surgery was 1.56 - 1.15 Dsph in Tan EndoGlide group and 1.18 +/- 1.10 Dsph in Busin Glide group (P 0.05). Mean CDVA was 0.65+/- 0.27 and 0.63 +/- 0.25, respectively (P>0,05). Statistically significant differences in intra- and post-operative complications between both groups were not found. The Tan EndoGlide used during posterior lamellar keratoplasty with DSEK technique is a good alternative to currently used methods. It provides better stabilization of the anterior chamber, however its use is linked with higher postoperative astigmatism in comparison with Busin Glide. The visual outcomes and endothelial cell loss 6 months after the surgery were similar in both groups.

An “All-laser” Endothelial Transplant

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Rossi, Francesca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Pini, Roberto; Menabuoni, Luca

2015-01-01

The “all laser” assisted endothelial keratoplasty is a procedure that is performed with a femtosecond laser used to cut the donor tissue at an intended depth, and a near infrared diode laser to weld the corneal tissue. The proposed technique enables to reach the three main goals in endothelial keratoplasty: a precise control in the thickness of the donor tissue; its easy insertion in the recipient bed and a reduced risk of donor lenticule dislocation. The donor cornea thickness is measured in the surgery room with optical coherence tomography (OCT), in order to correctly design the donor tissue dimensions. A femtosecond laser is used to cut the donor cornea. The recipient eye is prepared by manual stripping of the descemetic membrane. The donor endothelium is inserted into a Busin-injector, the peripheral inner side is stained with a proper chromophore (a water solution of Indocyanine Green) and then it is pulled in the anterior chamber. The transplanted tissue is placed in the final and correct location and then diode laser welding is induced from outside the eyeball. The procedure has been performed on more than 15 patients evidencing an improvement in surgery performances, with a good recovery of visual acuity and a reduced donor lenticule dislocation event. PMID:26167711

Femtosecond laser cutting of endothelial grafts: comparison of endothelial and epithelial applanation.

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Bernard, Aurélien; He, Zhiguo; Gauthier, Anne Sophie; Trone, Marie Caroline; Baubeau, Emmanuel; Forest, Fabien; Dumollard, Jean Marc; Peocʼh, Michel; Thuret, Gilles; Gain, Philippe

2015-02-01

Stromal surface quality of endothelial lamellae cut for endothelial keratoplasty with a femtosecond laser (FSL) with epithelial applanation remains disappointing. Applanation of the endothelial side of the cornea, mounted inverted on an artificial chamber, has therefore been proposed to improve cut quality. We compared lamellar quality after FSL cutting using epithelial versus endothelial applanation. Lamellae were cut with an FSL from organ-cultured corneas. After randomization, 7 were cut with epithelial applanation and 7 with endothelial applanation. Lamellae of 50-, 75-, and 100-μm thickness were targeted. Thickness was measured by optical coherence tomography before and immediately after cutting. Viable endothelial cell density was quantified immediately after cutting using triple labeling with Hoechst/ethidium/calcein-AM coupled with image analysis with ImageJ. The stromal surface was evaluated by 9 masked observers using semiquantitative scoring of scanning electronic microscopy images. Histology of 2 samples was also analyzed before lamellar detachment. Precision (difference in target/actual thickness) and thickness regularity [coefficient of variation (CV) of 10 measurements] were significantly better with endothelial applanation (precision: 18 μm; range, 10-30; CV: 11%; range, 8-12) than with epithelial applanation (precision: 84 μm; range, 54-107; P = 0.002; CV: 24%; range, 13-47; P = 0.001). Endothelial applanation provided thinner lamellae. However, viable endothelial cell density was significantly lower after endothelial applanation (1183 cells/mm2; range, 787-1725 versus 1688 cells/mm2; range, 1288-2025; P = 0.018). FSL cutting of endothelial lamellae using endothelial applanation provides thinner more regular grafts with more predictable thickness than with conventional epithelial applanation but strongly reduces the pool of viable endothelial cells.

Diagnosis and Management of Iridocorneal Endothelial Syndrome

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Sacchetti, Marta; Mantelli, Flavio; Macchi, Ilaria; Ambrosio, Oriella; Rama, Paolo

2015-01-01

The iridocorneal endothelial (ICE) syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of “ICE-cells” on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty. PMID:26451377

MMSC-LIKE LIMBAL CELLS COTRANSPLANTATION PROMOTES LOCAL IMMUNOCORRECTION AND CORNEAL GRAFT TRANSPARENT RETENTION IN HIGH RISK KERATOPLASTY

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S. A. Borzenok

2014-01-01

Full Text Available Aim was to evaluate clinical results of donor corneal graft survival in high-risk recipients in co-transplantation of preserved allogenic limbal grafts. Materials and methods. Two types of penetrative keratoplasties were carried out in patients with corneal graft opacities and high risk of rejection (n = 69. Co-transplantation of donor cornea and allogenic MMSC-like limbal cells in the form of limbal transplants was carried out in the 1st group (n = 36; in the 2nd group (n = 33 only the cornea was transplanted. Results. Observation of the patients during one year after surgery showed that the rate of transparent cornea engraftment increased in the 1st group (86,1 against 69,7% in the 2nd group. The density of endothelial cells was also higher in the 1st group (85,9 against 76,2% in the 2nd group. At the same time, progressive decreasing of pro-inflammatory cytokines (IL-6, IFNγ, TNFα and increasing of anti-inflammatory cytokines (IL-10, IL-1RA, TGFβ along with higher level of HLA-G5 were revealed in the recipients’ tear fluid in the 1st group in comparison to the 2nd group. Conclusion. Simultaneous transplantation of preserved limbal grafts with corneal graft in high-risk keratoplasty favors the transparent cornea engraftment, obviously, this is due to immunoregulatory activity of the MMSC-like limbal cells. 

In situ ultrahigh-resolution optical coherence tomography characterization of eye bank corneal tissue processed for lamellar keratoplasty.

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Brown, Jamin S; Wang, Danling; Li, Xiaoli; Baluyot, Florence; Iliakis, Bernie; Lindquist, Thomas D; Shirakawa, Rika; Shen, Tueng T; Li, Xingde

2008-08-01

To use optical coherence tomography (OCT) as a noninvasive tool to perform in situ characterization of eye bank corneal tissue processed for lamellar keratoplasty. A custom-built ultrahigh-resolution OCT (UHR-OCT) was used to characterize donor corneal tissue that had been processed for lamellar keratoplasty. Twenty-seven donor corneas were analyzed. Four donor corneas were used as controls, whereas the rest were processed into donor corneal buttons for lamellar transplantation by using hand dissection, a microkeratome, or a femtosecond laser. UHR-OCT was also used to noninvasively characterize and monitor the viable corneal tissue immersed in storage medium over 3 weeks. The UHR-OCT captured high-resolution images of the donor corneal tissue in situ. This noninvasive technique showed the changes in donor corneal tissue morphology with time while in storage medium. The characteristics of the lamellar corneal tissue with each processing modality were clearly visible by UHR-OCT. The in situ characterization of the femtosecond laser-cut corneal tissue was noted to have more interface debris than shown by routine histology. The effects of the femtosecond laser microcavitation bubbles on the corneal tissue were well visualized at the edges of the lamellar flap while in storage medium. The results of our feasibility study show that UHR-OCT can provide superb, in situ microstructural characterization of eye bank corneal tissue noninvasively. The UHR-OCT interface findings and corneal endothelial disc thickness uniformity analysis are valuable information that may be used to optimize the modalities and parameters for lamellar tissue processing. The UHR-OCT is a powerful approach that will allow us to further evaluate the tissue response to different processing techniques for posterior lamellar keratoplasty. It may also provide information that can be used to correlate with postoperative clinical outcomes. UHR-OCT has the potential to become a routine part of tissue

Modified Descemet’s Stripping Automated Endothelial Keratoplasty: The Use of Ophthalmic Viscoelastic Devices in Hypotonic Eyes That Had Undergone Glaucoma Filtering Surgeries

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Itaru Oyakawa

2018-01-01

Full Text Available Purpose. Descemet’s stripping automated endothelial keratoplasty (DSAEK is more difficult in hypotonic eyes with filtering bleb, due to the difficulties in elevating the intraocular pressure (IOP. We report a new method that uses ophthalmic viscoelastic devices (OVDs to achieve good graft adhesion. Case Presentation. We performed modified DSAEK surgery on 2 eyes of 2 patients, who had previously undergone a trabeculectomy. Both eyes had functioning filtering blebs; the IOP was lower than 10 mmHg without medication. After the graft was inserted into the anterior chamber, the conjunctiva was penetrated, apart from the bleb, using a 30 G needle, and Healon V® was injected into the bleb until the encapsulated space was filled completely. Air was subsequently injected into the anterior chamber to promote the graft attachment to the back surface of the cornea. The IOP was elevated above 40 mmHg in both eyes 1 h after surgery and then decreased to less than 30 mmHg over the subsequent 3 h period. The implanted graft showed good adhesion and no dislocation. Conclusions. Our novel DSAEK procedure that adds one step of OVD injection into the filtering bleb may be useful for hypotonic eyes that had undergone filtering surgeries.

Deep anterior lamellar keratoplasty in the management of keratoconus

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Rajesh Fogla

2013-01-01

Full Text Available Advanced cases of keratoconus often require surgical intervention to restore corneal anatomy and improve eyesight. Penetrating keratoplasty (PK although commonly performed has potential risk of immunological rejection and is now no longer automatically the first choice of surgery. DALK procedures have evolved, which allows surgical replacement of recipient′s corneal stroma, leaving behind healthy descemet membrane (DM and endothelium. This reduces the risk of allograft endothelial rejection and late graft failure. In recent times, DALK techniques have led to significant improvements in visual outcome and current results are comparable to PK. Big bubble technique of DALK has become the most popular among the various surgical techniques described. Manual near DM DALK also gives good outcome although the visual recovery is often delayed. Future integration of femtosecond laser technology along with diagnostic imaging technology is likely to further improve outcomes of DALK in keratoconus.

[Interlamellar sectoral keratoplasty in the surgical correction of astigmatism].

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Frolov, M A; Beliaev, V S; Dushin, N V; Kravchinina, V V; Barashkov, V I; Gonchar, P A

1996-01-01

A new original method of interlamellar sectorial keratoplasty is proposed for surgical correction of astigmatism. Eleven operations were carried out in 8 patients (11 eyes) with astigmatism of 4 to 7.0 diopters. Vision acuity without correction was 0.6 to 1.0 in 5 patients (7 eyes, 63.6%). In 2 patients (2 eyes, 18.2%) vision acuity without correction was 0.3 to 0.5 diopters, and in 2 more patients (2 eyes, 18.2%) it was from 0.1 to 0.3 diopters, that is, equal to the maximal vision acuity with the optimal correction. The refraction effect stabilized in 3-4 months. The highest refraction effect attained was 7.0 diopters. The patients were followed up for 3 months to 4 years. Clinical analysis of the operations confirmed the efficacy and reliability of the method and stability of refraction. Interlamellar sectorial keratoplasty is recommended for surgical correction of astigmatism.

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

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Natalia Vázquez

Full Text Available Corneal keratoplasty (penetrating or lamellar using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of

Infectious crystalline keratopathy caused by Cladosporium sp. after penetrating keratoplasty: a case report

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Stock RA

2016-08-01

emphasizes the clinical characteristics and outcome of this type of keratitis. Keywords: cornea, keratitis, Cladosporium, penetrating keratoplasty, corneal ulcer

Combined keratoplasty and cataract extraction.

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Demeler, U; Hinzpeter, E N

1977-04-01

A short film showing our technique of combined penetrating keratoplasty and intracapsular cataract extraction was shown, and the postoperative results in 72 eyes after an average of 3 years were reported.

Contact Lens Visual Rehabilitation in Keratoconus and Corneal Keratoplasty

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Yelda Ozkurt

2012-01-01

Full Text Available Keratoconus is the most common corneal distrophy. It’s a noninflammatory progressive thinning process that leads to conical ectasia of the cornea, causing high myopia and astigmatism. Many treatment choices include spectacle correction and contact lens wear, collagen cross linking, intracorneal ring segments implantation and finally keratoplasty. Contact lenses are commonly used to reduce astigmatism and increase vision. There are various types of lenses are available. We reviewed soft contact lenses, rigid gas permeable contact lenses, piggyback contact lenses, hybrid contact lenses and scleral-semiscleral contact lenses in keratoconus management. The surgical option is keratoplasty, but even after sutur removal, high astigmatism may stil exists. Therefore, contact lens is an adequate treatment option to correct astigmatism after keratoplasty.

Development of a nomogram for femtosecond laser astigmatic keratotomy for astigmatism after keratoplasty.

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St Clair, Ryan M; Sharma, Anushree; Huang, David; Yu, Fei; Goldich, Yakov; Rootman, David; Yoo, Sonia; Cabot, Florence; Jun, Jason; Zhang, Lijun; Aldave, Anthony J

2016-04-01

To develop a nomogram for femtosecond laser astigmatic keratotomy (AK) to treat post-keratoplasty astigmatism. Three academic medical centers. Retrospective interventional case series. A review of post-keratoplasty femtosecond laser AK was performed. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, and keratometry were recorded preoperatively and 1, 3, 6, and 12 months postoperatively. The location, length, depth, and diameter of the AK incisions were recorded, and the surgically induced astigmatic correction was related to these variables using regression analysis. One hundred forty femtosecond laser AK procedures were performed after penetrating keratoplasty (PKP) (n = 129) or deep anterior lamellar keratoplasty (DALK) (n =11), with 89 procedures (80 PKP, 9 DALK) included in the analysis. The mean CDVA improved from 20/59 (0.47 logMAR ± 0.38 [SD]) preoperatively to 20/45 (0.35 ± 0.31 logMAR) postoperatively (P = .013) (n = 46). The mean keratometric astigmatism decreased from 8.26 ± 2.90 diopters (D) preoperatively to 3.62 ± 2.59 D postoperatively (P AK to treat post-keratoplasty astigmatism was generated using regression analysis. Femtosecond laser AK significantly improved UDVA and CDVA and significantly reduced keratometric astigmatism and refractive cylinder after keratoplasty. The nomogram generated should improve the accuracy of post-keratoplasty femtosecond laser AK. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Corneal endothelium in xeroderma pigmentosum: clinical specular microscopy study.

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Mohamed, Ashik; Peguda, Rajini; Ramappa, Muralidhar; Ali, Mohammad Javed; Chaurasia, Sunita

2016-06-01

Xeroderma pigmentosum is a condition caused due to a defective DNA repair mechanism when exposed to ultraviolet radiation. Many of the patients with this disorder develop severely oedematous cornea with varying degrees of anterior corneal haze, which necessitates a full-thickness keratoplasty or selective endothelial keratoplasty. Presence of corneal oedema suggests that these patients have a dysfunctional endothelium. The purpose of this study is to evaluate the corneal endothelium in the patients with xeroderma pigmentosum when clinical specular microscopy was feasible. Thirteen patients with classic skin changes of xeroderma pigmentosum were included in the study conducted during January 2010-December 2012. An age-matched group of 13 volunteers were included as controls who were emmetropes without any history of ocular or systemic illness. Corneal endothelium was assessed using specular microscopy from the central clear area of cornea. The mean age of the patients with xeroderma pigmentosum was 16.6±7.2 years and that of the controls was 17.4±6.9 years (p=0.78). The number of analysed cells and endothelial cell density were significantly higher in controls (pxeroderma pigmentosum (p≤0.007). The specular microscopic findings in patients with xeroderma pigmentosum are suggestive of an accelerated endothelial cell loss. It is pertinent that the treating physicians must be involved in emphasising proper ocular protection from ultraviolet radiation to prevent avoidable blindness from xeroderma pigmentosum. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Novel method to avoid the open-sky condition in penetrating keratoplasty: covered cornea technique.

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Arslan, Osman S; Unal, Mustafa; Arici, Ceyhun; Cicik, Erdoğan; Mangan, Serhat; Atalay, Eray

2014-09-01

The aim of this study was to present a novel technique to avoid the open-sky condition in pediatric and adult penetrating keratoplasty (PK). Seventy-two eyes of 65 infants and children and 44 eyes of 44 adult patients were operated on using this technique. After trephining the recipient cornea up to a depth of 50% to 70%, the anterior chamber was entered at 1 point. Then, only a 2 clock hour segment of the recipient button was incised, and this segment was sutured to the recipient rim with a single tight suture. The procedure was repeated until the entire recipient button was excised and resutured. The donor corneal button was sutured to the recipient corneal rim. The sutures between the recipient button and the rim were then cut off, and the recipient button was drawn out. None of the patients operated on with this technique developed complications related to the open-sky condition. Visual acuities, graft failure rates, and endothelial cell loss were comparable with the findings of studies performed for conventional PK. The technique described avoids the open-sky condition during the entire PK procedure. Endothelial cell loss rates are acceptable.

Evaluation of corneal biomechanical properties following penetrating keratoplasty using ocular response analyzer

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Vanathi Murugesan

2014-01-01

Full Text Available Purpose: To evaluate corneal biomechanical properties in eyes that has undergone penetrating keratoplasty (PK. Materials and Methods: Retrospective observational study in a tertiary care centre. Data recorded included ocular response analyzer (ORA values of normal and post-keratoplasty eyes [corneal hysteresis (CH, corneal resistance factor (CRF, Goldmann-correlated intraocular pressure (IOPg, and cornea-compensated intraocular pressure (IOPcc], corneal topography, and central corneal thickness (CCT. Wilcoxon signed rank test was used to analyze the difference in ORA parameter between post-PK eyes and normal eyes. Correlation between parameters was evaluated with Spearman′s rho correlation. Results: The ORA study of 100 eyes of 50 normal subjects and 54 post-keratoplasty eyes of 51 patients showed CH of 8.340 ± 1.85 and 9.923 ± 1.558, CRF of 8.846 ± 2.39 and 9.577 ± 1.631 in post-PK eyes and normal eyes, respectively. CH and CRF did not correlate with post-keratoplasty astigmatism (P = 0.311 and 0.276, respectively while a significant correlation was observed with IOPg (P = 0.004 and IOPcc (P < 0.001. Conclusion: Biomechanical profiles were significantly decreased in post-keratoplasty eyes with significant correlation with higher IOP as compared with that in normal eyes.

Real-time assessment of corneal endothelial cell damage following graft preparation and donor insertion for DMEK.

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Maninder Bhogal

Full Text Available To establish a method for assessing graft viability, in-vivo, following corneal transplantation.Optimization of calcein AM fluorescence and toxicity assessment was performed in cultured human corneal endothelial cells and ex-vivo corneal tissue. Descemet membrane endothelial keratoplasty grafts were incubated with calcein AM and imaged pre and post preparation, and in-situ after insertion and unfolding in a pig eye model. Global, macroscopic images of the entire graft and individual cell resolution could be attained by altering the magnification of a clinical confocal scanning laser microscope. Patterns of cell loss observed in situ were compared to those seen using standard ex-vivo techniques.Calcein AM showed a positive dose-fluorescence relationship. A dose of 2.67μmol was sufficient to allow clear discrimination between viable and non-viable areas (sensitivity of 96.6% with a specificity of 96.1% and was not toxic to cultured endothelial cells or ex-vivo corneal tissue. Patterns of cell loss seen in-situ closely matched those seen on ex-vivo assessment with fluorescence viability imaging, trypan blue/alizarin red staining or scanning electron microscopy. Iatrogenic graft damage from preparation and insertion varied between 7-35% and incarceration of the graft tissue within surgical wounds was identified as a significant cause of endothelial damage.In-situ graft viability assessment using clinical imaging devices provides comparable information to ex-vivo methods. This method shows high sensitivity and specificity, is non-toxic and can be used to evaluate immediate cell viability in new grafting techniques in-vivo.

Femtosecond laser-assisted keratoplasty in a child with corneal opacity:case report

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E. Yu. Markova

2014-01-01

Full Text Available Corneal opacities are the fourth cause of blindness world-wide. Over the past two centuries, various corneal transplantation (i.e., keratoplasty methods have been developed and improved. Nowadays, femtolaserssisted keratoplasty is one of most promising techniques. Femtosecond laser have several advantages that provide additional surgical benefits. Among them, no thermal injury, the ability to cut deeply on a single plane and to perform various corneal profiles should be mentioned. In children, corneal disorders are of special importance while femtosecondassisted keraatoplasty case reports are rare. Here, we describe femtosecond laserssisted penetrating keratoplasty in a girl with a rough central corneal opacity.

A clinical comparison of the Xpert non-contact tonometer with the Goldmann applanation tonometer after penetrating keratoplasty.

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Lisle, C; Ehlers, N

2000-04-01

To assess the agreement between the Xpert non-contact tonometer (NCT) and the Goldmann applanation tonometer in patients who have undergone penetrating keratoplasty. The study material consisted of 42 consecutive patients (43 eyes) who had undergone penetrating keratoplasty within the previous 13 months. The slope of the linear relationship between the two measurement methods did not differ significantly from 1.0. The mean difference between the methods of 0.96 mmHg was not statistically significant. The range of intraindividual differences between the methods was from -9.8 to 22.8 mmHg. The standard deviation of differences was 6.62 mmHg. The 95% limits of agreement were -12.00 to 13.94 mmHg. There was no significant correlation between the central corneal thickness, astigmatism or transplant size and the difference between the methods The Xpert NCT shows considerable variation from the Goldmann values The degree of agreement with the true IOP value remains to be shown.

STUDY OF THE ANATOMICAL AND VISUAL RESULTS OF THERAPEUTIC PENETRATING KERATOPLASTY

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Chhaya Ashok Shinde

2017-03-01

Full Text Available BACKGROUND Therapeutic penetrating keratoplasty for corneal infections restores anatomical integrity. Improvement in instrumentation and surgical techniques, better postoperative management have improved corneal transplant outcome. Purpose of the study was to know what are the anatomical and visual results after therapeutic keratoplasty and to judge what could be the factors affecting the results. MATERIALS AND METHODS Prospective, non-comparative, observational cohort study was done in 56 patient (56 eyes operated for therapeutic penetrating keratoplasty at tertiary care institute .Patients were reviewed for demographic data, postoperative best-corrected visual acuity, graft clarity, and complications. Pre-operative treatment in bacterial infections included Cefazolin 50 mg/ml and Tobramycin 1.4 % or gentamicin 1.4% half hourly, 1% atropine drops. Fungal infections were treated with Natamycin 5% suspension. Debridement was done. Amphotericin B was used against yeasts. Voriconazole (1% eye drops were given in Aspergillus species. With full aseptic precautions penetrating keratoplasty was carried out. The graft was 0.5 mm larger than the lesion. Keratoplasties were evaluated for (1 Graft clarity at 1 month and 1 year postoperative. (2 Cure of the infectious disease after surgery. (3 Anatomical success rate and visual results. RESULTS At the end of one year clear graft with bacterial keratitis was seen in 23 eyes (74.19% out of 31 eyes. In fungal keratitis clear graft was seen in 10 eyes (45.45% out of 22 eyes. 48.22% patients had vision of FC 1m-6/60 compared to preoperative vision at the end of one year. At the end of one year anatomical integrity was maintained in 53 (94.64% cases and it was lost in 5.36% patients. CONCLUSION Patients who underwent keratoplasty with 7.5 mm graft size had maximum graft clarity at the end of one year. Graft was clear in 36 patients (64.29% out of total 56 patients. At the end of 1 year vision improved to FC 1 mt

Evaluation of the Role of Umbilical Cord Serum and Autologous Serum Therapy in Reepithelialization After Keratoplasty: A Randomized Controlled Clinical Trial.

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Kamble, Neha; Sharma, Namrata; Maharana, Prafulla K; Bandivadekar, Pooja; Nagpal, Ritu; Agarwal, Tushar; Velpandian, Thirumurthy; Mittal, Suneeta; Vajpayee, Rasik B

2017-09-01

To evaluate the role of umbilical cord serum (UCS) and autologous serum (AS) therapy in reepithelialization of corneal graft after keratoplasty in a randomized controlled trial. A total of 105 eyes with epithelial defect (ED) after keratoplasty (penetrating keratoplasty-67 and anterior lamellar keratoplasty-38) on the first postoperative day were included in the study. The eyes were randomized into three groups: UCS (n=35), AS (n=35), and artificial tears (AT) (n=35). All patients received standard postoperative medical therapy. The primary outcome measure was time to epithelialization, and secondary outcome measures were best-corrected visual acuity and graft clarity. The ED healed completely in 103 eyes. The mean time for complete reepithelialization was 2.5±2.1, 3.1±2.2, and 4.5±1.4 days in UCS, AS, and AT groups, respectively. The mean percentage decrease in the size of the ED was significantly better in the UCS and AS groups as compared with the AT group (P=0.001). The rate of reepithelialization was comparable between the AS and UCS groups (P=0.3). On bivariate analysis, significant correlation was found between the mean size of postoperative ED, grade of the donor cornea (P=0.001), and the presence of preoperative ED (P=0.001). No complications were associated with the use of serum therapy. Most of the cases of postkeratoplasty corneal ED can be managed with AT only. The serum therapy (AS/UCS) helps in the faster reepithelialization of postkeratoplasty ED as compared with AT and may be considered as a treatment option for early epithelial healing.

[Interlamellar circular keratoplasty for correction of high myopia].

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Beliaev, V S; Dushin, N V; Gonchar, P A; Frolov, M A; Barashkov, V I; Kravchinina, V V; Balikoev, T M

1995-01-01

A new method is proposed for the correction of high myopia: Interlamellar circular keratoplasty. This method has been used in 15 patients (17 eyes) aged 18 to 54 with 9 to 17 diopters myopia. Vision acuity attained was at least 0.5 in 10 (60.3%) patients; in 7 (35.2%) patients vision acuity was 0.3 without correction, that is, was equal to the maximal vision acuity with the optimal correction. The highest refraction effect was 15.0 diopters. The patients were followed up for 3 months to 16 years. The proposed method for the correction of high myopia is highly effective, simple, and is recommended for clinical practice.

Femtosecond laser enabled keratoplasty for advanced keratoconus

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Yathish Shivanna

2013-01-01

Full Text Available Purpose : To assess the efficacy and advantages of femtosecond laser enabled keratoplasty (FLEK over conventional penetrating keratoplasty (PKP in advanced keratoconus. Materials and Methods: Detailed review of literature of published randomized controlled trials of operative techniques in PKP and FLEK. Results: Fifteen studies were identified, analyzed, and compared with our outcome. FLEK was found to have better outcome in view of better and earlier stabilization uncorrected visual acuity (UCVA, best corrected visual acuity (BCVA, and better refractive outcomes with low astigmatism as compared with conventional PKP. Wound healing also was noticed to be earlier, enabling early suture removal in FLEK. Conclusions: Studies relating to FLEK have shown better results than conventional PKP, however further studies are needed to assess the safety and intraoperative complications of the procedure.

Laser in situ keratomileusis for residual hyperopic astigmatism after conductive keratoplasty.

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Kymionis, George D; Aslanides, Ioannis M; Khoury, Aghlab N; Markomanolakis, Marinos M; Naoumidi, Tatiana; Pallikaris, loannis G

2004-01-01

To report a case of laser in situ keratomileusis (LASIK) in a patient with previous conductive keratoplasty. A 48-year-old man underwent conductive keratoplasty for low hyperopic astigmatism (manifest refraction OD: +2.25 -0.50 x 77 degrees; OS: +2.50 -0.50 x 105 degrees). Three months postoperatively, UCVA was 20/25 and BSCVA was 20/20 in both eyes; manifest refraction OD: -0.25 -0.75 x 110 degrees; OS: +0.75 -0.75 x 50 degrees. Sixteen months after the operation, regression of refractive outcome was (manifest) OD: +1.75 -1.25 x 90 degrees; OS: +2.50 -0.50 x 85 degrees; UCVA was 20/40 in the right eye and 20/63 in the left eye and BSCVA was 20/20 in both eyes. LASIK was performed for hyperopic regression in the left eye using an automated microkeratome (Alcon SKBM, 130-microm plate; Aesculap-Meditec MEL 70 excimer laser). LASIK was uneventful and no intraoperative or postoperative complications related to the previous conductive keratoplasty procedure or LASIK were observed. Three months after LASIK and 19 months after the initial conductive keratoplasty, the patient's left eye was emmetropic; UCVA was 20/20(-2), BSCVA was 20/20 and manifest refraction was +0.25 -0.25 x 35 degrees. There was a uniform increase in topographical steepening. Visual acuity, refraction and topographic findings remained unchanged at 6 months. Even though our experience is limited, treatment of hyperopia with LASIK in an eye with refractive regression following previous conductive keratoplasty resulted in a predicted refractive outcome, with no complications, and improvement in visual acuity at 6 months follow-up.

The use of postoperative slit-lamp optical coherence tomography to predict primary failure in descemet stripping automated endothelial keratoplasty.

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Shih, Carolyn Y; Ritterband, David C; Palmiero, Pat-Michael; Seedor, John A; Papachristou, George; Harizman, Noga; Liebmann, Jeffrey M; Ritch, Robert

2009-05-01

To determine if central donor lenticle thickness as measured by slit-lamp optical coherence tomography (SL OCT; Heidelberg Engineering, Heidelberg, Germany) is predictive of primary donor failure in patients undergoing Descemet stripping automated endothelial keratoplasty (DSAEK). Retrospective cross-sectional study. Eighty-four patients who underwent DSAEK surgery by 2 surgeons (D.C.R. and J.A.S.) were enrolled. At each postoperative visit (postoperative day 1, week 1, month 1, and month 2), an SL OCT scan was obtained. Statistical differences in SL OCT measurements of successful and failed DSAEK procedures were measured using the Student t test. A successful DSAEK surgery was defined as having an anatomically attached, clear recipient corneal stroma and donor lenticle compatible with good vision 2 months after surgery. A failed DSAEK surgery was defined as an attached donor lenticle with SL evidence of corneal edema and thickening visible at 2 months or more. Ninety-three eyes of 84 consecutive patients who underwent DSAEK surgery also underwent postoperative SL OCT. After 2 months of follow-up, 82 (88%) procedures were successful and 11 (12%) procedures were failures. The average donor lenticle thickness in successful DSAEK eyes was 314 +/- 128 microm on postoperative day 1 as compared with failed DSAEK eyes, which averaged 532 +/- 259 microm (P = .0013). This was independent regardless of whether the lenticle was attached on the first postoperative visit. Seventy-nine (98%) successful DSAEK eyes had a lenticle thickness of or = 350 microm at the 1-week postoperative visit. Statistically significant differences in SL OCT thickness measurements were seen between successful and failed DSAEK cases at all examinations after postoperative week 1. Corneal thickness measurements made with SL OCT are an important predictor of DSAEK failure in both attached and detached lenticles within the first week of surgery. DSAEK lenticle thickness of 350 microm or less at 1 week

Ahmed glaucoma valve in post-penetrating-keratoplasty glaucoma: A critically evaluated prospective clinical study

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Panda, Anita; Prakash, Vadivelu Jaya; Dada, Tanuj; Gupta, Anoop Kishore; Khokhar, Sudarshan; Vanathi, Murugesan

2011-01-01

Aim: The aim was to evaluate the outcome of Ahmed glaucoma valve (AGV) in post-penetrating-keratoplasty glaucoma (PKPG). Materials and Methods: In this prospective study, 20 eyes of 20 adult patients with post-PKPG with intraocular pressure (IOP) >21 mmHg, on two or more antiglaucoma medications, underwent AG (model FP7) implantation and were followed up for a minimum of 6 months. Absolute success was defined as 5 glaucoma managed by AGV implantation revealed a satisfactory outcome up to 6 months of follow-up. PMID:21586837

Accuracy of Corneal Thickness by Swept-Source Optical Coherence Tomography and Scheimpflug Camera in Virgin and Treated Fuchs Endothelial Dystrophy.

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Arnalich-Montiel, Francisco; Ortiz-Toquero, Sara; Auladell, Clara; Couceiro, Ana

2018-06-01

To assess intraobserver repeatability, intersession reproducibility, and agreement of swept-source Fourier-domain optical coherence tomography (SS-OCT) and the Scheimpflug camera in measuring corneal thickness in virgin and grafted eyes with Fuchs endothelial corneal dystrophy (FECD). Thirty-six control eyes, 35 FECD eyes, 30 FECD with corneal edema eyes, 25 Descemet stripping automated endothelial keratoplasty (DSAEK) eyes, and 29 Descemet membrane endothelial keratoplasty (DMEK) eyes were included. The apical center, pupillary center, and thinnest corneal thickness were determined in 3 consecutive images and repeated 2 weeks later. Repeatability and reproducibility coefficients, intraclass correlation coefficients, and 95% limits of agreement (LOA) between measurements were calculated. Agreement between devices was assessed using Bland-Altman analysis. Corneal thickness measurements were highly reproducible and repeatable with both systems. SS-OCT showed better repeatability in all corneal locations in the normal, FECD, FECD with edema, DSAEK, and DMEK groups (coefficient of variation ≤0.60%, ≤0.36%, ≤0.43%, ≤1.09%, and ≤0.48%, respectively) than the Scheimpflug (coefficient of variation ≤1.15%, ≤0.92%, ≤1.10%, ≤1.25%, and ≤1.14%, respectively). Between-session 95% LOA for SS-OCT was less than 3% for all groups except for the FECD with edema group, being almost double using the Scheimpflug camera. Differences between instruments were statistically significant in all groups and locations (P group (P ≤ 0.51); however, SS-OCT underestimated all measurements. SS-OCT provides better reproducible and repeatable measurements of corneal thickness than those obtained with the Scheimpflug camera in patients with FECD or an endothelial transplant. Variations between examinations higher than the 95% LOA observed in our study should raise awareness of changes in the endothelial function.

Indications and Visual Outcome of Penetrating Keratoplasty in Tertiary Eye Care Institute in Uttarakhand

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Gupta, Neeti; Dhasmana, Renu; Nagpal, Ramesh Chander; Bahadur, Harsh; Maitreya, Amit

2016-01-01

Introduction Corneal blindness forms significant proportion of visual blindness in developing countries and penetrating keratoplasty (PK) can restore vision for this. The prognosis of PK is dependent on the corneal diseases responsible for corneal blindness. Aim To evaluate the indications and visual outcome of PK in tertiary eye care institute in Uttarakhand. Materials and Methods Data was reviewed from the medical records of 145 PK done in Department of Ophthalmology, Himalayan Institute of Medical Sciences from January 2012 to October 2014. Analysis of data was done for evaluation of the indications and visual outcome by Paired student’s t-test for hypothesis testing of grouped values of preoperative and last follow-up best corrected visual acuity in cases of optical and therapeutic grafts. A p-value < 0.05 was considered statistically significant. Results In this study data of 145 eyes of 138 patients was reviewed. The most common indication for keratoplasty was corneal scarring including adherent leucoma 48 (33.10%). Therapeutic keratoplasty was done for 33 cases with maximum 30(20.68%) cases of infectious keratitis. One case of tectonic graft was included in therapeutic keratoplasty group for analysis. There was statistically significant difference (p=.0001) in best corrected visual acuity improvement from 1.39 logMAR+ 0.022(SD) preoperatively to 0.367 logMAR+0.44(SD) postoperatively and 1.4 logMAR+.000(SD) preoperatively to 0.16 logMAR+0.57(SD) postoperatively for optical and therapeutic grafts respectively. Conclusion Infective keratitis either active or healed was the major indication for keratoplasty. Poor prognosis indications were most common in this part of the country. The visual outcome following corneal transplantation was encouraging particularly in cases of optical keratoplasty. PMID:27504319

Complications and Management of Deep Anterior Lamellar Keratoplasty

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Banu Torun Acar

2014-10-01

Full Text Available Objectives: To report the intraoperative and postoperative follow-up complications and management of these in deep anterior lamellar keratoplasty (DALK surgery. Materials and Methods: Two hundred eighty-four eyes of 252 patients followed up in our cornea clinic who underwent DALK using Anwar’s big-bubble technique with healthy Descemet’s membrane and endothelium were included in this study. Intraoperative and postoperative complications as well as the management and treatment of these complications were evaluated. Results: Big bubble was created in 220 (77.5% eyes of 284 eyes, and lamellar dissection was performed in 64 (22.5% eyes. Perforation occurred during trephination in 4 eyes, and the procedure was accomplished by penetrating keratoplasty (PK. Intraoperative microperforation occurred in 44 eyes. Perforation enlarged in 4 eyes and PK was performed. Operation was continued in 40 eyes with air injection into the anterior chamber. In postopertive follow-up period, double anterior chamber (DAC occurred in 32 of 40 eyes. DAC spontaneously regressed in 8 eyes, and air was given into the anterior chamber with a second surgical intervention in 24 eyes. DAC improved in 20 eyes. Four eyes underwent PK. Fungal keratitis evolved at the interface in one eye, because of no healing during the follow-up period, this eye underwent PK under antifungal therapy. Eyes with interface haze and Descemet’s membrane folds were followed. Conclusion: DALK is a difficult technique with a steep learning curve. In addition to the complications seen in PK, specific complications can occur in lamellar surgery. (Turk J Ophthalmol 2014; 44: 337-40

Black diaphragm intraocular lens implantation and penetrating keratoplasty in aphakic eyes with traumatic aniridia

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Xiao-Guang Dong

2013-04-01

Full Text Available AIM: To evaluate the long-term outcome of implantation of black diaphragm intraocular (BDI lens combined with penetrating keratoplasty (PKP for managing aphakic eyes with traumatic aniridia and corneal damage. METHODS: Six aphakic eyes of six patients with traumatic aniridia and corneal damage had BDI lens implantation at Qingdao Eye Hospital, Shandong Eye Institute from June 2008 to November 2011. Medical records of the patients were reviewed. Three patients received PKP and after 12-18months were implanted with BDI lens. The other three patients completed PKP and BDI lens implantation at the same time. The corrected visual acuity, intraocular pressure and number of corneal endothelial cells were monitored. RESULTS: The patients were followed up for an average of 24.3±12.1months (range 14-48 months. All BDI lenses were located well. The best corrected visual acuity got improved in 5 patients (0.1-1.0 and decreased in 1 patient from 0.4 to 0.2. Three patients had normal intraocular pressure (IOP after implantation. Two patients required antiglaucoma medications to control IOP within the normal range and 1 patient implanted Ahmed glaucoma valve to control IOP. The corneal grafts kept transparent in all eyes and the corneal endothelial counting >1 000/mm2, although two patients experienced acute graft rejection and loss more than 30% corneal endothelial cells. CONCLUSION: Implantation of BDI lens combined with PKP is an effective option for managing aphakic eyes with traumatic aniridia and corneal damage. Although the results in our study are encouraging, additional studies of the long-term safety and efficacy are required. A larger study population and longer follow-up may be beneficial.

Simultaneous topography-guided PRK followed by corneal collagen cross-linking after lamellar keratoplasty for keratoconus

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Spadea L

2012-11-01

Full Text Available Leopoldo Spadea,1 Marino Paroli21University of L’Aquila, Department of Biotechnological and Applied Clinical Sciences, Eye Clinic, L’Aquila, 2La Sapienza University, Department of Biotechnology and Medical-Surgical Sciences, Latina, ItalyBackground: The purpose of this paper is to report the results of using combined treatment of customized excimer laser-assisted photorefractive keratectomy (PRK and prophylactic corneal collagen crosslinking (CXL for residual refractive error in a group of patients who had previously undergone lamellar keratoplasty for keratoconus.Methods: The study included 14 eyes from 14 patients who had originally been treated for keratoconus in one eye by excimer laser-assisted lamellar keratoplasty (ELLK, and subsequently presented with residual ametropia (-6.11 D ± 2.48, range -2.50 to -9.50. After a mean 40.1 ± 12.4 months since ELLK they underwent combined simultaneous corneal regularization treatment with topographically guided transepithelial excimer laser PRK (central corneal regularization and corneal CXL induced by riboflavin-ultraviolet A.Results: After a mean 15 ± 6.5 (range 6–24 months, all eyes gained at least one Snellen line of uncorrected distance visual acuity (range 1–10. No patient lost lines of corrected distance visual acuity, and four patients gained three lines of corrected distance visual acuity. Mean manifest refractive spherical equivalent was -0.79 ± 2.09 (range +1 to -3.0 D, and topographic keratometric astigmatism was 5.02 ± 2.93 (range 0.8–8.9 D. All the corneas remained clear (haze < 1.Conclusion: The combination of customized PRK and corneal CXL provided safe and effective results in the management of corneal regularization for refractive purposes after ELLK for keratoconus.Keywords: corneal collagen crosslinking, excimer laser-assisted lamellar keratoplasty, photorefractive keratectomy

Remote manipulation of posterior lamellar corneal grafts using a magnetic field.

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Nahum, Yoav; Barliya, Tilda; Bahar, Irit; Livnat, Tami; Nisgav, Yael; Weinberger, Dov

2013-06-01

In posterior lamellar keratoplasty procedures such as Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, the lamellar graft is manipulated directly or by injecting an air bubble. This preliminary study sought to evaluate the feasibility of guiding lamellar corneal grafts by generating a magnetic field. Rabbit and porcine Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty grafts were manually produced and immersed in a ferromagnetic solution containing nanomagnetic particles conjugated to streptavidin or in gadoteric acid. For the feasibility study, grafts were transferred to an artificial anterior chamber or plastic test tube and a magnetic field was generated with a handheld NdFeB disc magnet. The presence and the sustainability of graft motion were documented under various conditions. For the semiquantitative study, whole or partial grafts were transferred to a plastic test tube after immersion, and the amount of tissue retraction induced by the remote magnet was graded. The grafts were successfully manipulated in all directions by the magnet, from a distance of up to 7 mm. They remained ferromagnetic more than 24 hours after immersion in the ferromagnetic solutions. The degree of retraction was affected by graft size, immersion time, time from immersion, and immersion solution. Posterior lamellar corneal grafts may be made ferromagnetic and remotely manipulated by creation of a magnetic field. The ferromagnetic properties are adjustable. This technique holds promise in attaching and repositioning grafts during keratoplasty. Further research is needed to assess the possible effects of ferromagnetic solutions on corneal endothelial cells and on lamellar graft clarity.

Excimer laser-assisted anterior lamellar keratoplasty for keratoconus, corneal problems after laser in situ keratomileusis, and corneal stromal opacities.

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Bilgihan, Kamil; Ozdek, Sengül C; Sari, Ayça; Hasanreisoğlu, Berati

2006-08-01

To evaluate excimer laser-assisted anterior lamellar keratoplasty to augment thin corneas as in keratoconus ( .05). This technique presents a different modality for the treatment of keratoconus, post-LASIK corneal problems, and other corneal stromal opacities with anterior lamellar keratoplasty. Additional studies with more patients and longer follow-up will help determine the role of this technique as a substitute for penetrating keratoplasty in these patients.

The value-based medicine comparative effectiveness and cost-effectiveness of penetrating keratoplasty for keratoconus.

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Roe, Richard H; Lass, Jonathan H; Brown, Gary C; Brown, Melissa M

2008-10-01

To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. Penetrating keratoplasty for patients with severe keratoconus seems to be a

A new vision through combined osteo-odonto-keratoplasty: A review

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Lakshmi Shetty

2014-01-01

Full Text Available This is an extensive review of osteo-odonto-keratoplasty (OOKP where the vision is restored by using tooth as an implant in the environment of the eye. The window of the soul is our eye and the window of the eye is cornea. This review article aims at discussing the remarkable operation to regain the sight of patients with corneal blindness. In this procedure where a multidisciplinary approach from both oral and maxillofacial surgeon and ophthalmologist contributes to restore vision in the most severe cases of corneal blindness. This involves removing a canine tooth from the patient, shaping and drilling to allow implantation of an artificial plastic corneal device and finally implanting back into the eye few months later. The OOKP, is the keratoprosthesis of choice for end-stage corneal blindness not amenable to penetrating keratoplasty. This transplantation procedure has an autologous dental root-bone lamina complex and buccal mucosal graft to secure the optical cylinder which acts as a ray of vision for corneal blindness. This review comprises the indications, contraindications, and patient assessment and the surgical procedure, complications ,surgical inter professionalism and future scope of OOKP. The source of data for the review has been Pubmed, Medline and all the research studies and published reports on osteo-odonto-keratoplasty. In this complex procedure good results can be obtained with modern technology and expertise.

Indications for Corneal Transplantation at a Tertiary Referral Center in Tehran

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Mohammad Zare

2010-01-01

Full Text Available Purpose: To report the indications and techniques of corneal transplantation at a tertiary referral center in Tehran over a 3-year period. Methods: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran from March 2004 to March 2007 were reviewed to determine the indications and types of corneal transplantation. Results: During this period, 776 eyes of 756 patients (including 504 male subjects with mean age of 41.3±21.3 years underwent corneal transplantation. The most common indication was keratoconus (n=317, 40.8% followed by bullous keratopathy (n=90, 11.6%, non-herpetic corneal scars (n=62, 8.0%, infectious corneal ulcers (n=61, 7.9%, previously failed grafts (n=61, 7.9%, endothelial and stromal corneal dystrophies (n=28, 3.6%, and trachoma keratopathy (n=26, 3.3%. Other indications including Terrien′s marginal degeneration, post-LASIK keratectasia, trauma, chemical burns, and peripheral ulcerative keratitis constituted the rest of cases. Techniques of corneal transplantation included penetrating keratoplasty (n=607, 78.2%, deep anterior lamellar keratoplasty (n=108, 13.9%, conventional lamellar keratoplasty (n=44, 5.7%, automated lamellar therapeutic keratoplasty (n=8, 1.0%, and Descemet stripping endothelial keratoplasty (n=6, 0.8% in descending order. The remaining cases were endothelial keratoplasty and sclerokeratoplasty. Conclusion: In this study, keratoconus was the most common indication for penetrating keratoplasty which was the most prevalent technique of corneal transplantation. However, deep anterior lamellar keratoplasty is emerging as a growing alternative for corneal pathologies not involving the endothelium.

Spontaneous wound dehiscence after penetrating keratoplasty

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Alireza Foroutan

2014-10-01

Full Text Available Spontaneous wound separation may be developed even months after suture removal especially in the context of long-term corticosteroid therapy. A 68-year-old Caucasian woman presented to our cornea clinic with spontaneous wound dehiscence after her third penetrating keratoplasty (PKP which was performed three years ago. An Ahmed glaucoma valve (New World Medical, Ranchos Cucamonga, CA was inserted ten months after the third PKP, which successfully controlled intraocular pressure (IOP. At the examination, the last sutures were removed eight months ago and she was using flourometholone 0.1 % (Sina Darou, Tehran, Iran with a dose of once a day. There was one quadrant of wound dehiscence from 8 to 11 o`clock associated with anterior wound gape and severe corneal edema. Resuturing was performed for the patient. At the one month examination, the corneal edema was resolved and best corrected visual acuity was 20/200 mainly due to previous glaucomatous optic neuropathy. Caution about the prolonged use of corticosteroids is necessary. Topical immunosuppressives could be a promising choice in this field.

Resultados e indicações de ceratoplastias penetrantes realizadas por médicos em treinamento, num país em desenvolvimento Indications and results of penetrating keratoplasty performed by training physicians in a developing country

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Marta Ferrari Teixeira

2001-11-01

- "Hospital de Base", in terms of indication for penetrating keratoplasty and final visual acuity. The minimum follow-up to assess the final visual acuity was 6 months. The cases of penetrating keratoplasty were divided into 6 groups of preoperative diagnosis for better comparison and statistical analysis of the final visual acuity. Such groups were: keratoconus, pseudophakic bullous keratopathy, aphakic bullous keratopathy, Fuchs' endothelial distrophy, band keratopathy and leukomas. All surgeries were performed by residents under supervision. Results: Keratoconus was the group that reached the highest average increase of postoperative lines of visual acuity (7.55 ± 2.83 and band keratopathy the smallest one (0.33 ± 3.20. A significant difference was observed among the indications for penetrating keratoplasty when compared to developed countries, where keratoconus is the most predominant indication. Our analysis revealed that the most important indications for penetrating keratoplasty in decreasing order were: leukoma, pseudophakic bullous keratopathy, keratoconus, Fuchs' endothelial distrophy, aphakic bullous keratopathy and band keratopathy. Conclusion: Keratoconus showed significant difference of final visual acuity levels (p value < 0,05 when compared to the other 5 groups of penetrating keratoplasty indications.

Ceratoplastia penetrante e glaucoma Penetrating keratoplasty and glaucoma

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Márcio Eulálio Barreto Soares

2007-08-01

Full Text Available O objetivo deste artigo é discutir os conhecimentos atuais sobre a abordagem clínica e terapêutica da ceratoplastia penetrante e do glaucoma a ela associado.The aim of this article is to make a review about glaucoma associated with penetrating keratoplasty, describing since its incidence and risk factors until the different options for treatment.

Nebivolol: impact on cardiac and endothelial function and clinical utility

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Toblli JE

2012-03-01

Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

Keratorefractive Effect of High Intensity Focused Ultrasound Keratoplasty on Rabbit Eyes

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Zhiyu Du

2016-01-01

Full Text Available Purpose. To evaluate high intensity focused ultrasound (HIFU as an innovation and noninvasive technique to correct presbyopia by altering corneal curvature in the rabbit eye. Methods. Eighteen enucleated rabbit eyes were treated with a prototype HIFU keratoplasty. According to the therapy power, these eyes were divided three groups: group 1 (1 W, group 2 (2 W, and group 3 (3 W. The change in corneal power was quantified by a Sirius Scheimpflug camera. Light microscopy (LM and transmission electron microscopy (TEM were performed to determine the effect on the corneal stroma. Results. In the treated eyes, the corneal curvature increases from 49.42 ± 0.30 diopters (D and 48.00 ± 1.95 D before procedure to 51.37 ± 1.11 D and 57.00 ± 1.84 D after HIFU keratoplasty application in groups 1 and 3, respectively. The major axis and minor axis of the focal region got longer when the powers of the HIFU got increased; the difference was statistically significant (p<0.05. LM and TEM showed HIFU-induced shrinkage of corneal stromal collagen with little disturbance to the underlying epithelium. Conclusions. We have preliminarily exploited HIFU to establish a new technique for correcting presbyopia. HIFU keratoplasty will be a good application prospect for treating presbyopia.

A case of acute postoperative keratitis after deep anterior lamellar keratoplasty by multidrug resistant Klebsiella

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Leena Bajracharya

2015-01-01

Full Text Available A healthy lady of 42 years underwent deep anterior lamellar keratoplasty for granular dystrophy. The very next day, it was complicated by development of infectious keratitis. The organism was identified as multidrug resistant Klebsiella pneumoniae. Donor corneal button may be implicated in the transmission of infection in an otherwise uneventful surgery and follow-up. Nosocomial infections are usually severe, rapidly progressive and difficult to treat. Finally, the lady had to undergo therapeutic penetrating keratoplasty for complete resolution of infection.

Collagen crosslinking for ectasia following PRK performed in excimer laser-assisted keratoplasty for keratoconus.

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Spadea, Leopoldo

2012-01-01

To report the results of corneal collagen crosslinking (CXL) in a patient with corneal ectasia developed after excimer laser-assisted lamellar keratoplasty for keratoconus and a secondary photorefractive keratectomy (PRK) for residual refractive error. A 33-year-old woman, who had originally been treated for keratoconus in the right eye by excimer laser-assisted lamellar keratoplasty, subsequently had her residual ametropia treated by topographically guided, transepithelial excimer laser PRK. Five years after PRK, the patient developed corneal ectasia showing concomitant visual changes of best spectacle-corrected visual acuity (BSCVA) reduced to 20/33 with a refraction of -6.00 +6.00 × 30. The minimum corneal thickness at the ectasia apex was 406 µm. A treatment of riboflavin-UVA-induced corneal CXL was performed on the right eye. Two years after the CXL treatment, the right eye improved to 20/20 BSCVA with a refraction of plano +1.00 × 50 while exhibiting a clear lamellar graft. Corneal CXL provided safe and effective management of ectasia developed after excimer laser-assisted lamellar keratoplasty and PRK.

Microkeratome-assisted lamellar keratoplasty for keratoconus: stromal sandwich.

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Bilgihan, Kamil; Ozdek, Sengül C; Sari, Ayça; Hasanreisoglu, Berati

2003-07-01

To evaluate microkeratome-assisted lamellar keratoplasty for the treatment of keratoconus when it is not possible to correct the astigmatic ametropia with contact lenses. Ophthalmology Department, School of Medicine, Gazi University, Ankara, Turkey. This prospective study comprised 9 eyes of 7 keratoconus patients with contact lens intolerance. The donor cornea was prepared with a microkeratome and punched with a 7.25 mm or 7.50 mm trephine. Following the creation of a standard 9.0 mm corneal flap in the host cornea, the donor stromal button was implanted under this corneal flap like a sandwich. Transepithelial photorefractive keratectomy or laser in situ keratomileusis was performed when the corneal topography and refraction stabilized by the end of the sixth postoperative month. Follow-up ranged from 7 to 22 months. All patients gained 5 or more lines (mean 7.2 lines +/- 1.6 [SD]), and no patient lost a line of vision. The mean corneal thickness was 432.7 +/- 36.1 micrometers preoperatively and 578.1 +/- 45.1 micrometers after refractive surgery. The early visual results of this surgical technique are promising and seem to be comparable to those with penetrating keratoplasty.

Indications and outcomes of pediatric keratoplasty in a tertiary eye care center: A retrospective review.

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Gulias-Cañizo, Rosario; Gonzalez-Salinas, Roberto; Hernandez-Zimbron, Luis Fernando; Hernandez-Quintela, Everardo; Sanchez-Huerta, Valeria

2017-11-01

To evaluate indications and outcomes of pediatric keratoplasty in a tertiary eye center, and identify factors that affect visual outcomes.We performed a retrospective review of penetrating keratoplasty in children aged 0 to 18 years between 1995 and 2011 in the Asociación para Evitar la Ceguera en México IAP, Hospital "Dr. Luis Sánchez Bulnes".A total of 574 penetrating keratoplasties were performed during the study interval. Median follow-up was 5.0 years. Main indications included keratoconus (55.58%), postherpetic scarring (9.58%), traumatic opacities (7.49%), and bullous keratopathy (6.09%). Rejection rates at 5 years were 27% overall, and among indications, keratoconus showed the best graft survival at 60-months follow-up (85%). The percentage of patients with best corrected visual acuity (BCVA) posttransplant >20/400 at 5 years in the nonrejection group was 81.25% and 82.74% in 10 years of age (YOA) groups, respectively, versus a BCVA posttransplant > 20/400 at 5 years in the rejection group of 53.68% and 51.72% in 10 YOA groups, respectively. There was a statistically significant reduced rejection rate between genders at 18 months of follow-up, favoring males.Despite being considered a high-risk procedure in children, penetrating keratoplasty can achieve good results, especially in patients with keratoconus. It can achieve significative improvements of visual acuity, provided there is an adequate follow-up and treatment adherence.

Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil

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Nina Ni

2015-01-01

Full Text Available Purpose. To present the clinical and histopathologic correlation of two cases of epithelial downgrowth (EDG after prior intraocular surgery. Methods. Observational case reports. Results. We present two cases of EDG occurring after intraocular surgery. In both cases, after two anterior chamber injections of 5-fluorouracil (5FU, the area of EDG initially regressed. In Case 1, a limited area of EDG eventually recurred, and penetrating keratoplasty with cryotherapy was curative. In Case 2, subsequent corneal edema required Descemet-stripping automated endothelial keratoplasty, and the patient remained clinically free of EDG without further treatment. Conclusion. Intracameral 5FU may have a role in the treatment of EDG after intraocular surgery, though its precise utilization and impact remain to be defined.

Glaucoma associated with iridocorneal endothelial syndrome in 203 Indian subjects.

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Premanand Chandran

Full Text Available To report the demographic profile, clinical features, and prevalence of glaucoma and its management in patients with Iridocorneal endothelial (ICE syndrome.Retrospective review of 203 consecutive subjects with ICE syndrome at a tertiary eye care centre between January 1988 and June 2013.ICE syndrome was present in 223 eyes of 203 subjects, 124 (61% were female and 79 (39% were male. The median age at presentation was 43 years (1st (Q1 and 3rd (Q3 quartile; 34, 51 years. ICE syndrome was unilateral in 183 (90% subjects, and bilateral in 20 (10% subjects. The most common clinical variant was progressive iris atrophy (PIA, 115; 52% eyes, followed by Chandler syndrome (CS, 87; 39% eyes and Cogan-Reese syndrome (CRS, 21; 9% eyes. Glaucoma was found in 156 eyes (70% at presentation and the median (Q1, Q3 intraocular pressure in eyes with glaucoma was 24 (16, 38 mm Hg. Seven eyes developed glaucoma during the follow-up period, increasing the percentage of eyes with glaucoma to 73%. Intraocular pressure was managed medically in 81 eyes (50% and the other 82 eyes (50% required surgical intervention. Corneal edema was present in 124 eyes (56% of which, 32 eyes (14% required keratoplasty.In our study on ICE syndrome in Indian population, the presentation was predominantly uniocular and more common in middle aged women. Progressive iris atrophy was the most common clinical variant. ICE syndrome was associated with glaucoma in over 70% of the eyes and half of the eyes had corneal edema.

Preparation of pre-cut corneas from fresh donated whole globes for Descemet's stripping automated keratoplasty: 3-year results at the Central Eye Bank of Iran.

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Kanavi, Mozhgan Rezaei; Javadi, Mohammad Ali; Javadi, Fatemeh; Chamani, Tahereh

2014-09-01

To describe the technique and the results of the preparation of pre-cut corneas for Descemet's stripping automated endothelial keratoplasty (DSAEK) during a 3-year period at the Central Eye Bank of Iran (CEBI). The method of preparation of pre-cut corneas from donated whole globes at the CEBI is described and the frequency and percentage of pre-cut corneas prepared for DSAEK, between April 2009 and March 2012, are specified. Moreover, post-operative reports are reviewed for any complaints about using pre-cut tissues for DSAEK. Out of the 1,518 donated whole globes appropriate for DSAEK, 1,478 (97.4 %) pre-cut corneas were successfully prepared. The method of preparation failed in 40 (2.6 %) cases. Based on the eye bank post-operative reports, thickness of pre-cut tissues for DSAEK was deemed unacceptable in only 6 (0.4 %) cases prior to surgery; five of these were too thick and one was too thin. Preparation of pre-cut corneas, for DSAEK from donated whole globes, in the CEBI is a safe and easy method, with very good preservation of endothelial cells after the preparation of the pre-cut corneas and reduced risks from corneal manipulation.

Keratomycosis caused by Acremonium Recifei, treated with keratoplasty, Miconazole and Ketoconazole

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H.J. Simonsz (Huib)

1983-01-01

textabstractA patient is discussed who developed a fungal corneal ulcer due to Acremonium (Cephalosporium) Recifei after a piece of a coconut flew into his eye while he was cracking it. Treatment consisted of keratoplasty, Miconazole as ointment and intravenously, and Ketaconazole orally. Diagnosis

Comparison the post operative refractive errors in same size corneal transplantation through deep lamellar keratoplasty and penetrating keratoplasty methods after sutures removing in keratoconus patients

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Hasan Razmjoo

2016-01-01

Full Text Available Background: Corneal transplantation is a surgery in which cornea is replaced by a donated one and can be completely penetrating keratoplasty (PK or included a part of cornea deep lamellar keratoplasty (DLK. Although the functional results are limited by some complications, it is considered as one of the most successful surgeries. This study aimed to compare the refractive errors after same size corneal transplantation through DLK and PK methods in keratoconus patients over 20 years. Materials and Methods: This descriptive, analytical study was conducted in Feiz Hospital, Sadra and Persian Clinics of Isfahan in 2013–2014. In this study, 35 patients underwent corneal transplantation by PK and 35 patients by DLK, after removing the sutures, the patients were compared in terms of best corrected visual acuity (BCVA and refractive errors. Data were analyzed using Chi-square and t Student tests by SPSS software. Results: The BCVA mean in DLK and PK groups was 6/10 ± 2/10 and 5/10 ± 2/10, respectively, with no significant difference (P = 0.4. The results showed 9 cases of DLK and 6 cases of PK had normal (8/10 ≤ BCVA visual acuity (25.7% vs. 17.1%, 24 cases of DLK and 27 cases of PK had mild vision impairment (68.6% vs. 77.1% and 2 cases of the DLK group and 2 cases of PK had moderate vision impairment, (5.7% vs. 5.7%, there was no significant difference in “BCVA” (P = 0.83. Conclusions: Both methods were acceptably effective in improving BCVA, but according to previous articles (5,9,10 the DLK method due to fewer complications and less risk of rejection was superior to another method and in the absence of any prohibition this method is recommended.

Explore the full thick layer of corneal transplantation in the treatment of pseudomonas aeruginosa corneal ulcer infection

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Xin Wang

2015-02-01

Full Text Available AIM: To explore the feasibility, safety and effect of the full-thickness lamellar keratoplasty for the treatment of pseudomonas aeruginosa corneal ulcer. METHODS: Based on a retrospective non-controlled study, 25 patients were given the full-thickness lamellar keratoplasty for clinical diagnosis of pseudomonas aeruginosa infection and corneal ulcer medication conventional anti-gram-negative bacteria. Routine follow-up were carried out at postoperative 1wk; 1, 3, 6, 12, 18mo to observe the situation of corneal epithelial healing, recurrent infection, immune rejection, graft transparency and best corrected visual acuity, etc. At the 6 and 12mo postoperative, corneal endothelial cell density was reexamined.RESULTS: No patients because of Descemet's membrane rupture underwent penetrating keratoplasty surgery: One only in cases of bacterial infection after 1mo, once again did not cultivate a culture of bacteria pseudomonas aeruginosa, and the remaining 24 cases average follow-up 14±6mo, corneal graft were transparent, the cure rate was 96%. At the sixth month after surgery, there were 16 cases of eye surgery best corrected visual acuity ≥4.5, of which 3 cases ≥4.8. At the sixth month after surgery, the average corneal endothelial cell density 2 425±278/mm2; At 12mo postoperatively, it was 2 257± 326/mm2.CONCLUSION: Full-thickness lamellar keratoplasty is an effective method of pseudomonas aeruginosa infection in the treatment of corneal ulcers, corneal drying material glycerol can be achieved by visual effects.

An easy and inexpensive method for quantitative analysis of endothelial damage by using vital dye staining and Adobe Photoshop software.

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Saad, Hisham A; Terry, Mark A; Shamie, Neda; Chen, Edwin S; Friend, Daniel F; Holiman, Jeffrey D; Stoeger, Christopher

2008-08-01

We developed a simple, practical, and inexpensive technique to analyze areas of endothelial cell loss and/or damage over the entire corneal area after vital dye staining by using a readily available, off-the-shelf, consumer software program, Adobe Photoshop. The purpose of this article is to convey a method of quantifying areas of cell loss and/or damage. Descemet-stripping automated endothelial keratoplasty corneal transplant surgery was performed by using 5 precut corneas on a human cadaver eye. Corneas were removed and stained with trypan blue and alizarin red S and subsequently photographed. Quantitative assessment of endothelial damage was performed by using Adobe Photoshop 7.0 software. The average difference for cell area damage for analyses performed by 1 observer twice was 1.41%. For analyses performed by 2 observers, the average difference was 1.71%. Three masked observers were 100% successful in matching the randomized stained corneas to their randomized processed Adobe images. Vital dye staining of corneal endothelial cells can be combined with Adobe Photoshop software to yield a quantitative assessment of areas of acute endothelial cell loss and/or damage. This described technique holds promise for a more consistent and accurate method to evaluate the surgical trauma to the endothelial cell layer in laboratory models. This method of quantitative analysis can probably be generalized to any area of research that involves areas that are differentiated by color or contrast.

Endothelial function and dysfunction: clinical significance and assessment

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Shaghayegh Haghjooyejavanmard

2008-08-01

Full Text Available

• Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
•  KEYWORDS: Endothelial function, endothelium, Disease.

Clinical applications of corneal confocal microscopy

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Mitra Tavakoli

2008-06-01

Full Text Available Mitra Tavakoli1, Parwez Hossain2, Rayaz A Malik11Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; 2University of Southampton, Southampton Eye Unit, Southampton General Hospital, Southampton, UKAbstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy, and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.Keywords: corneal confocal microscopy, cornea, infective keratitis, corneal dystrophy, neuropathy

Femtosecond laser cutting of multiple thin corneal stromal lamellae for endothelial bioengineering.

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Bernard, Aurélien; He, Zhiguo; Forest, Fabien; Gauthier, Anne-Sophie; Peocʼh, Michel; Dumollard, Jean-Marc; Acquart, Sophie; Montard, Romain; Delbosc, Bernard; Gain, Philippe; Thuret, Gilles

2015-02-01

To assess the feasibility of cutting multiple thin stromal lamellae in human donor corneas using a commercial femtosecond laser (FSL) to provide cell carriers for future endothelial graft bioengineering. Eight edematous organ-cultured corneas not suitable for grafting for endothelial reasons were mounted on a Ziemer anterior chamber and cut with a Z6 FSL with 6 successive parallel cuts, from depth to surface. Target thickness of each lamella ranged from 100 to 150 μm depending on initial corneal thickness. Thickness was measured using anterior segment optical coherence tomography before and after cutting on mounted corneas, and on each stromal lamella after detachment. Scanning electron microscopy observation was performed on 4 lamellae and histological cross sections on 1 cornea before detachment. A median of 5 (minimum 3, maximum 7) lamellae was obtained per cornea. All lamellae still attached were the most posterior ones, suggesting that FSL was less efficient because of light scattering by edematous stroma. Cut precision and postdetachment swelling were correlated with anterior-posterior position within the cornea. Median lamella thickness was 127 μm (56-222 μm) before detachment and 196 μm (80-304 μm) after detachment. Surface state was consistent with previously reported FSL lamellar cuts during Descemet stripping automated endothelial keratoplasty. Up to 7 thin lamellae can be cut in stored corneas with an FSL. This method, once optimized primarily by using deswelled, more transparent corneas, could prove effective for recycling unsuitable donor corneas in corneal bioengineering processes.

[The role of endothelial cells and endothelial precursor cells in angiogenesis].

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Poreba, Małgorzata; Usnarska-Zubkiewicz, Lidia; Kuliczkowski, Kazimierz

2006-01-01

Endothelium plays a key role in maintenance of vascular homeostasis in human organism. According to new data endothelial cells and hematopoietic cells have a common precursor in prenatal life--a hemangioblast, which explains the fact of sharing the same determinants on the surface of both type of cells. Circulating endothelial precursors were identified in adults and this suggests that hemangioblasts may be present not only during embriogenesis. In some clinical situations the increased numbers of endothelial cells and endothelial precursors were noted, and especially in patients with neoplastic diseases, which is probably the result of increased angiogenesis. Endothelial precursors are thought to be the promice for therapeutic purposes in future--to increase local angiogenesis.

Sequential selective same-day suture removal in the management of post-keratoplasty astigmatism.

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Fares, U; Mokashi, A A; Elalfy, M S; Dua, H S

2013-09-01

In a previous study, we proposed that corneal topography performed 30-40 min after the initial suture removal can identify the next set of sutures requiring removal, for the treatment of post-keratoplasty astigmatism. The aim of this study was to evaluate the effect of removing subsequent sets of sutures at the same sitting. 10/0 nylon interrupted sutures were placed, to secure the graft-host junction, at the time of keratoplasty. Topography was performed using Pentacam (Oculus) before suture removal. The sutures to be removed in the steep semi-meridians were identified and removed at the slit-lamp biomicroscope. Topography was repeated 30-40 min post suture removal, the new steep semi-meridians determined, and the next set of sutures to be removed were identified and removed accordingly. Topography was repeated 4-6 weeks later and the magnitude of topographic astigmatism was recorded. A paired-samples t-test was used to evaluate the impact of selective suture removal on reducing the magnitude of topographic and refractive astigmatism. Twenty eyes of 20 patients underwent sequential selective same-day suture removal (SSSS) after corneal transplantation. This study showed that the topographic astigmatism decreased by about 46.7% (3.68 D) and the refractive astigmatism decreased by about 37.7% (2.61 D) following SSSS. Vector calculations also show a significant reduction of both topographic and refractive astigmatism (P<0.001). SSSS may help patients to achieve satisfactory vision more quickly and reduce the number of follow-up visits required post keratoplasty.

Intraocular pressure measurements after conductive keratoplasty.

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Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Kumar, Vinod; Astyrakakis, Nikolaos I; Tsilimbaris, Miltiadis; Pallikaris, Ioannis G

2005-01-01

To determine the possible impact of conductive keratoplasty (CK) on intraocular pressure (IOP) measurements. A prospective, single-center, noncomparative interventional case series was performed. Baseline and postoperative IOPs were measured by Goldmann applanation tonometry in 32 eyes of 18 patients who underwent CK for hyperopia correction. Mean follow-up was 11.9 months (range: 8 to 18 months). After CK, a statistically significant decrease in the measured IOP was observed (before CK: 14.22+/-1.64 vs after CK: 12.66+/-2.21, P<.001). The change in IOP readings postoperatively was not correlated with age, sex, keratometric readings, or attempted correction. Despite the limitations due to the small number of patients enrolled in this study, the applanation tonometer appears to underestimate the true IOP after CK.

[Astigmatic keratotomy with the femtosecond laser: correction of high astigmatisms after keratoplasty].

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Kook, D; Bühren, J; Klaproth, O K; Bauch, A S; Derhartunian, V; Kohnen, T

2011-02-01

The purpose of this study was to evaluate a novel technique for the correction of postoperative astigmatism after penetrating keratoplasty with the use of the femtosecond laser creating astigmatic keratotomies (femto-AK) in the scope of a retrospective case series. Clinical data of ten eyes of nine patients with high residual astigmatism after penetrating keratoplasty undergoing paired femto-AK using a 60-kHz femtosecond laser (IntraLase™, AMO) were analyzed. A new software algorithm was used to create paired arcuate cuts deep into the donor corneal button with different cut angles. Target values were refraction, uncorrected visual acuity, best corrected visual acuity, topographic data (Orbscan®, Bausch & Lomb, Rochester, NY, USA), and corneal wavefront analysis using Visual Optics Lab (VOL)-Pro 7.14 Software (Sarver and Associates). Vector analysis was performed using the Holladay, Cravy and Koch formula. Statistical analysis was performed to detect significances between visits using Student's t test. All procedures were performed without any major complications. The mean follow-up was 13 months. The mean patient age was 48.7 years. The preoperative mean uncorrected visual acuity (logMAR) was 1.27, best corrected visual acuity 0.55, mean subjective cylinder -7.4 D, and mean topometric astigmatism 9.3 D. The postoperative mean uncorrected visual acuity (logMAR) was 1.12, best corrected visual acuity 0.47, mean subjective cylinder -4.1 D, and mean topometric astigmatism 6.5 D. Differences between corneal higher order aberrations showed a high standard deviation and were therefore not statistically significant. Astigmatic keratotomy using the femtosecond laser seems to be a safe and effective tool for the correction of higher corneal astigmatisms. Due to the biomechanical properties of the cornea and missing empirical data for the novel femto-AK technology, higher numbers of patients are necessary to develop optimal treatment nomograms.

Ahmed glaucoma valve in post-penetrating-keratoplasty glaucoma: A critically evaluated prospective clinical study

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Anita Panda

2011-01-01

Full Text Available Aim: The aim was to evaluate the outcome of Ahmed glaucoma valve (AGV in post-penetrating-keratoplasty glaucoma (PKPG. Materials and Methods: In this prospective study, 20 eyes of 20 adult patients with post-PKPG with intraocular pressure (IOP >21 mmHg, on two or more antiglaucoma medications, underwent AG (model FP7 implantation and were followed up for a minimum of 6 months. Absolute success was defined as 5 < IOP < 21 mmHg and qualified success as 5 < IOP < 21 mmHg with medications or minor procedures. Results: The mean IOP decreased from 42.95 ± 10.24 to 17.69 ± 3.64 mmHg (P < 0.001 and the use of medications dropped from 2.92 to 0.39 (P < 0.001 after AGV implantation. The absolute success was achieved in 11 eyes and qualified success in 9. There was no significant change in best corrected visual acuity, graft clarity, or graft thickness. Six device-related complications occurred after AGV implantations which were successfully managed with medical or minor surgical therapy. Conclusions: Postkeratoplasty refractory glaucoma managed by AGV implantation revealed a satisfactory outcome up to 6 months of follow-up.

Image-guided modified deep anterior lamellar keratoplasty (DALK) corneal transplant using intraoperative optical coherence tomography

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Tao, Yuankai K.; LaBarbera, Michael; Ehlers, Justis P.; Srivastava, Sunil K.; Dupps, William J.

2015-03-01

Deep anterior lamellar keratoplasty (DALK) is an alternative to full-thickness corneal transplant and has advantages including the absence of allograft rejection; shortened duration of topical corticosteroid treatment and reduced associated risk of glaucoma, cataract, or infection; and enables use of grafts with poor endothelial quality. DALK begins by performing a trephination of approximately 80% stromal thickness, as measured by pachymetry. After removal of the anterior stoma, a needle is inserted into the residual stroma to inject air or viscoelastic to dissect Descemet's membrane. These procedures are inherently difficult and intraoperative rates of Descemet's membrane perforation between 4-39% have been reported. Optical coherence tomography (OCT) provides high-resolution images of tissue microstructures in the cornea, including Descemet's membrane, and allows quantitation of corneal layer thicknesses. Here, we use crosssectional intraoperative OCT (iOCT) measurements of corneal thickness during surgery and a novel micrometeradjustable biopsy punch to precision-cut the stroma down to Descemet's membrane. Our prototype cutting tool allows us to establish a dissection plane at the corneal endothelium interface, mitigates variability in cut-depths as a result of tremor, reduces procedure complexity, and reduces complication rates. iOCT-guided modified DALK procedures were performed on 47 cadaveric porcine eyes by non-experts and achieved a perforation rate of ~5% with a mean corneal dissection time care.

Diamond knife-assisted deep anterior lamellar keratoplasty to manage keratoconus.

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Vajpayee, Rasik B; Maharana, Prafulla K; Sharma, Namrata; Agarwal, Tushar; Jhanji, Vishal

2014-02-01

To evaluate the outcomes of a new surgical technique, diamond knife-assisted deep anterior lamellar keratoplasty (DALK), and compare its visual and refractive results with big-bubble DALK in cases of keratoconus. Tertiary eyecare hospital. Comparative case series. The visual and surgical outcomes of diamond knife-assisted DALK were compared with those of successful big-bubble DALK. Diamond knife-assisted DALK was performed in 19 eyes and big-bubble DALK, in 11 eyes. All surgeries were completed successfully. No intraoperative or postoperative complications occurred with diamond knife-assisted DALK. Six months after diamond knife-assisted DALK, the mean corrected distance visual acuity (CDVA) improved significantly from 1.87 logMAR ± 0.22 (SD) to 0.23 ± 0.06 logMAR, the mean keratometry improved from 65.99 ± 8.86 diopters (D) to 45.13 ± 1.16 D, and the mean keratometric cylinder improved from 7.99 ± 3.81 D to 2.87 ± 0.59 D (all P=.005). Postoperatively, the mean refractive astigmatism was 2.55 ± 0.49 D and the mean spherical equivalent was -1.97 ± 0.56 D. The mean logMAR CDVA (P = .06), postoperative keratometry (P=.64), refractive cylinder (P=.63), and endothelial cell loss (P=.11) were comparable between diamond knife-assisted DALK and big-bubble DALK. Diamond knife-assisted DALK was effective and predictable as a surgical technique for management of keratoconus cases. This technique has the potential to offer visual and refractive outcomes comparable to those of big-bubble DALK. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Evaluation of an interlaced triple procedure: penetrating keratoplasty, extracapsular cataract extraction, and nonopen-sky intraocular lens implantation.

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Yang, Shuo; Wang, Bin; Zhang, Yangyang; Zhai, Hualei; Wang, Junyi; Wang, Shuang; Xie, Lixin

2017-09-01

To evaluate an interlaced triple procedure that involved penetrating keratoplasty (PKP), extracapsular cataract extraction (ECCE) using diathermy capsulotomy, and nonopen-sky intraocular lens (IOL) implantation.This retrospective study involved data from 34 patients who were diagnosed with severe corneal opacities and cataracts. These patients were divided into an interlaced procedure group (21 patients) and a traditional procedure group (13 patients). In the interlaced group, the method of continuous curvilinear capsulorhexis (CCC) was completed via diathermy capsulotomy. The donor corneal button was sutured at 8 positions (at equal intervals) using 10-0 nylon sutures, and the IOL was inserted into the capsular bag using a closed anterior chamber approach at the 10:30 to 12 o'clock positions between the sutures. In the traditional group, CCC was completed using side-port capsular forceps, and the IOL was implanted using an open anterior chamber approach.In the interlaced group, the CCC, open-sky, and total operation times were significantly shorter than in the traditional group (P < .05). Neither the best-corrected visual acuity (BCVA) nor corneal endothelial cell density was significantly different between the groups at 1 and 6 months after the operation.This interlaced triple procedure for the treatment of corneal diseases with cataracts appears to be feasible and practical.

Endothelial-regenerating cells: an expanding universe.

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Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

2010-03-01

Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

Modified big-bubble technique compared to manual dissection deep anterior lamellar keratoplasty in the treatment of keratoconus.

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Knutsson, Karl Anders; Rama, Paolo; Paganoni, Giorgio

2015-08-01

To evaluate the clinical findings and results of manual dissection deep anterior lamellar keratoplasty (DALK) compared to a modified big-bubble DALK technique in eyes affected by keratoconus. Sixty eyes of 60 patients with keratoconus were treated with one of the two surgical techniques manual DALK (n = 30); big-bubble DALK (n = 30). The main outcomes measured were visual acuity, corneal topographic parameters, thickness of residual stroma and endothelial cell density (ECD). Patients were examined postoperatively at 1 month, 6 months, 1 year and 1 month after suture removal. Final best spectacle-corrected visual acuity (BSCVA) measured 1 month after suture removal was 0.11 ± 0.08 LogMAR in the big-bubble group compared to 0.13 ± 0.08 in the manual DALK group (p = 0.227). In patients treated with the big-bubble technique without complications (Descemet's membrane completely bared), the stromal residue was not measureable. Mean stromal residual thickness in the manual DALK group was 30.50 ± 27.60 μm. Data analysis of the manual DALK group demonstrated a significant correlation between BSCVA and residual stromal thickness; lower residual stromal thickness correlated with better BSCVA values (Spearman ρ = 0.509, p = 0.018). Postoperative ECD was similar in both groups at all intervals, with no statistically significant differences. In both groups, ECD loss was only significant during the 1- to 6-month interval (p = 0.001 and p big-bubble DALK and manual DALK groups, respectively). Manual DALK provides comparable results to big-bubble DALK. Big-bubble DALK permits faster visual recovery and is a surgical technique, which can be easily converted to manual DALK in cases of unsuccessful 'big-bubble' formation. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.

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Holland, Edward J; Lane, Stephen S; Kim, Terry; Raizman, Michael; Dunn, Steven

2008-04-01

To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.

Expression of Vascular Endothelial Growth Factor in Odontogenic Cysts: Is There Any Impression on Clinical Outcome?

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Sadri, Donia; Farhadi, Sareh; Shahabi, Zahra; Sarshar, Samaneh

2016-01-01

The recent scientific reports have shown that angiogenesis can affect biological behavior of pathologic lesions. Regarding unique clinical outcome of Odontogenic keratocyst (OKC), the present study was aimed to compare angiogenesis in Odontogenic keratocyst and Dentigerous cyst (DC). In this experimental study, tissue sections of 46 samples of OKC and DC were stained through immunohistochemical method using Vascular Endothelial Growth Factor (VEGF) antibody. VEGF expression was evaluated in epithelial cells, fibroblasts and endothelial cells. The average percentage of stained cells in any samples was categorized to 3 groups as follows: SCORE 0: 10% of cells or less are positive. SCORE 1: 10 to 50% of cells are positive. SCORE 2: more than 50% of cells are positive. Mann-U-Whitney, T-test and chi-square was used for statistical analysis. The average of VEGF expression in 24 samples of DC was 20.2% and in 22 samples of OKC was 52.6%, respectively. The average of VEGF expression in these two cysts had statistical significant differences. (PV= 0.045). There was significant statistical differences between two cysts in the terms of VEGF SCORE (PV= 0.000). OKC samples had significantly higher SCORE for the purpose of VEGF incidence than DC. Also, there were no differences between VEGF expression in epithelial cells of two cysts (PV= 0.268) there were significant statistical differences between two cysts in terms of endothelial cell staining. The endothelial cell staining was significantly higher in OKC than DC (PV= 0.037%). Regarding higher expression of Vascular Endothelial Growth factor in OKC than DC, it seems that angiogenesis may have great impression on clinical outcome of OKC.

Estudo retrospectivo dos transplantes penetrantes de córnea da Santa Casa de Porto Alegre Retrospective study of penetrating keratoplasty at the Santa Casa of Porto Alegre

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Caroline Fabris

2001-10-01

Full Text Available Objetivos: Traçar o perfil clínico e social dos pacientes submetidos a transplante de córnea e avaliar as principais indicações desses transplantes, tempo de espera para doação e os índices de sucesso, rejeição e falência dos transplantes penetrantes de córnea. Métodos: Foram analisados retrospectivamente os prontuários de 87 pacientes submetidos a transplante penetrante de córnea no Serviço de Oftalmologia da Santa Casa de Porto Alegre entre janeiro de 1990 e dezembro de 1998, totalizando 91 olhos. Destes, 56 pacientes foram chamados para avaliação clínica do enxerto durante o levantamento de dados para este estudo. Resultados: Considerando-se os 91 transplantes (87 pacientes, 53 (60,9% foram realizados em pacientes do sexo masculino e 34 (39%, do sexo feminino. A idade variou de 3 a 89 anos, com média de 42,3 ± 19,8 anos. As principais indicações para transplante de córnea foram ceratocone em 32 (35% olhos, ceratopatia bolhosa (pós-facectomia, distrofia de Fuchs e outros em 24 (26,4%, trauma mecânico em 9 (9,9%, causas infecciosas em 9 (9,9%, queimadura química em 2 (2,2%, queimadura térmica em 1 (1,1% e outras causas em 14 (15,4% olhos. O tempo médio de espera por doação de córnea foi de 17,3 ± 9,9 meses. Do total de 91 olhos transplantados, 25 (27,5% apresentaram rejeição e 12 (13,2% olhos apresentaram falência do transplante. Conclusões: Este estudo mostrou a epidemiologia dos pacientes transplantados. A falta de dados seriados devido à alta precoce e perda de acompanhamento dos pacientes tornou impossível a análise e a comparação dos resultados pós-operatórios com outros estudos.Purpose: To describe the clinical and social profile of recipient patients of transplanted corneas, and to evaluate main indications for corneal transplants, waiting time for donor tissue, and percentages of success, rejection and failure of penetrating keratoplasty. Methods: Retrospective chart review of 87 patients

Sustainability of Routine Notification and Request legislation on eye bank tissue supply and corneal transplantation wait times in Canada.

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Lee, Kenneth; Boimer, Corey; Hershenfeld, Samantha; Sharpen, Linda; Slomovic, Allan R

2011-10-01

To assess whether provinces with Routine Notification and Request (RNR) legislation have sustained increases in corneal tissue supply and decreases in wait times for corneal transplantation surgery. Cross-sectional survey of Canadian corneal transplant (CT) surgeons and eye banks. Canadian CT surgeons and representatives from the 10 Canadian eye banks. Voluntary and anonymous surveys were distributed between July and October 2009. Eligible CT surgeons were defined as ophthalmologists who practice in Canada; currently perform Penetrating keratoplasty (PKP), Deep anterior lamellar keratoplasty (DALK), Deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet membrane endothelial keratoplasty (DMEK); and have obtained tissues from a Canadian eye bank. From 2006 to 2009, for provinces with RNR legislation and where data are available, mean wait times from date of diagnosis to date of CT surgery have increased: in Ontario, from 31 ± 34 weeks to 36 ± 27 weeks; in British Columbia, from 39 ± 20 weeks to 42 ± 35 weeks; in Manitoba, from 32 ± 23 weeks to 49 ± 36 weeks. In addition, the amount of corneal tissue in RNR provinces suitable for transplant, with the exception of British Columbia, has declined between 2006 and 2008: in Ontario, 1186 tissues to 999 tissues (16% decline); in Manitoba, 92 tissues to 83 tissues (10% decline); in New Brunswick, 129 tissues to 98 tissues (24% decline). Although initially effective, RNR legislation has not sustained an increase in corneal tissue availability nor has it shortened wait times in most provinces. Incorporation of community hospitals into the RNR catchment, improved enforcement, and continued education of hospital staff regarding the RNR process may be effective in making this legislation more sustainable in the long term. Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Novel spatula and dissector for safer deep anterior lamellar keratoplasty

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Gustavo ,2,3 Bonfadini

2014-10-01

Full Text Available Objective: We describe a novel spatula and dissector to facilitate the big-bubble technique in deep anterior lamellar keratoplasty (DALK. Methods: A 29-year-old man who was diagnosed with bilateral keratoconus underwent deep anterior lamellar keratoplasty (DALK. After 350μm partial thickness incision of the recipient cornea, the Bonfadini dissector was inserted at the deepest point in the peripheral incision and could be advanced to the center of the cornea safely because of its "semi-sharp" tip. After achieving the big-bubble (BB separation of Descemet membrane (DM from the overlying stroma, the anterior stromal disc was removed. Viscoelastic material was placed on the stromal bed to prevent uncontrolled collapse and perforation of DM during the paracentesis blade incision into the BB. We could detect the safe opening of the BB using the Bonfadini dissector by the leakage of air bubbles into the viscoelastic material. After injecting viscoelastic material into the BB space, we inserted the Bonfadini spatula into the bigbubble safely because of its curved profile and blunt edges. The groove along the length of the Bonfadini spatula enables safe and efficient incision or the residual stromal tissue using the pointed end of a sharp blade while protecting the underlying DM. After removal of posterior stroma, the donor button was sutured with 16 interrupted 10-0 nylon sutures. Results: This technique and the use of the Bonfadini spatula and dissector facilitate exposure of Descemet membrane. Conclusion: The smooth Bonfadini DALK spatula and dissector facilitate safe and efficient completion of DALK surgery.

Da Vinci Xi Robot-Assisted Penetrating Keratoplasty.

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Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-06-01

This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5-61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use.

Da Vinci Xi Robot–Assisted Penetrating Keratoplasty

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Chammas, Jimmy; Sauer, Arnaud; Pizzuto, Joëlle; Pouthier, Fabienne; Gaucher, David; Marescaux, Jacques; Mutter, Didier; Bourcier, Tristan

2017-01-01

Purpose This study aims (1) to investigate the feasibility of robot-assisted penetrating keratoplasty (PK) using the new Da Vinci Xi Surgical System and (2) to report what we believe to be the first use of this system in experimental eye surgery. Methods Robot-assisted PK procedures were performed on human corneal transplants using the Da Vinci Xi Surgical System. After an 8-mm corneal trephination, four interrupted sutures and one 10.0 monofilament running suture were made. For each procedure, duration and successful completion of the surgery as well as any unexpected events were assessed. The depth of the corneal sutures was checked postoperatively using spectral-domain optical coherence tomography (SD-OCT). Results Robot-assisted PK was successfully performed on 12 corneas. The Da Vinci Xi Surgical System provided the necessary dexterity to perform the different steps of surgery. The mean duration of the procedures was 43.4 ± 8.9 minutes (range: 28.5–61.1 minutes). There were no unexpected intraoperative events. SD-OCT confirmed that the sutures were placed at the appropriate depth. Conclusions We confirm the feasibility of robot-assisted PK with the new Da Vinci Surgical System and report the first use of the Xi model in experimental eye surgery. Operative time of robot-assisted PK surgery is now close to that of conventional manual surgery due to both improvement of the optical system and the presence of microsurgical instruments. Translational Relevance Experimentations will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use. PMID:28660096

Safety of prophylactic intracameral moxifloxacin ophthalmic solution after cataract surgery in patients with penetrating keratoplasty

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Osman Sevki Arslan

2014-10-01

Full Text Available AIM:To determine the safety of prophylactic intracameral moxifloxacin after cataract surgery in patients with penetrating keratoplasty (PKP.METHODS:In this retrospective study of consecutive patients who had phacoemulsification cataract surgery after PKP, were treated with intracameral moxifloxacin 0.5% ophthalmic solution (0.5 mg/0.1 mL. The main outcome measures were anterior chamber reaction, best corrected visual acuity (BCVA, corneal endothelial cell count (ECC, and central corneal thickness (CCT.RESULTS:Fifty-five patients were recruited (26 males, 29 females. The mean age was 54.36±4.97y (range 45-64y. All eyes had improved postoperative BCVA. The mean BCVA was 0.25 preoperatively and 0.57 postoperatively, which was statistically significant (P<0.001. One eye had 3+, 7 eyes had 2+, 12 eyes had 1+ and 8 eyes had trace amount of aqueous cells on the first day after surgery. All eyes had no anterior chamber cells at subsequent follow up examinations. Effective phacoemulsification time was 4.33±1.01s. The mean ECC was 2340.20 cells/mm2 preoperatively and 1948.75 cells/mm2 1mo postoperatively (P<0.001. The increase of 21.09 µm in postoperative pachymetry 1mo after surgery was statistically significant (P<0.001.CONCLUSION: No untoward effects were observed after intracameral injection of moxifloxacin (0.5 mg/0.1 mL in terms of anterior chamber reaction, CCT, ECC, and visual rehabilitation at the conclusion of cataract surgery in patients with PKP.

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

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McCarthy, E M; Wilkinson, F L; Parker, B; Alexander, M Y

2016-11-01

Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Development prospects of keratoplasty in Moscow

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E. M. Kildyushov

2013-01-01

Full Text Available A retrospective analysis of the statistical data for the years 2010‑2012 on mortality and the donor selection of the Bureau of Forensic Pathology of Moscow, Department of Forensic Pathology of Pirogov N. I. Russian National Research Medical University and ILab Eye Bank in order to determine the possible number of keratoplastic surgeries. The results of statistical data analysis testify to the fact that the number of available donor material is not sufficient to meet the needs for keratoplastic material and it is necessary to create eye banks, which would have provided this need. It is necessary to create eye banks, that possess a clear logistics chain of intake donor tissue, preliminary assessment of the donor tissue, laboratory diagnostics of the donor’s blood and delivery of tissue to the Bank. Theeye bank should not only produce preserved material for keratoplasty, but also carry out full morpho-functional assessment of material and its subsequent delivery to consumers in health facilities.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

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Paulina Dumnicka

2017-02-01

Full Text Available Acute pancreatitis (AP is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1 we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2 we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

Mitochondria and Endothelial Function

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Kluge, Matthew A.; Fetterman, Jessica L.; Vita, Joseph A.

2013-01-01

In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease. PMID:23580773

Targeted endothelial nanomedicine for common acute pathological conditions.

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Shuvaev, Vladimir V; Brenner, Jacob S; Muzykantov, Vladimir R

2015-12-10

Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal

Corneal collagen cross-linking in the stabilization of PRK, LASIK, thermal keratoplasty, and orthokeratology.

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Nguyen, Michelle K; Chuck, Roy S

2013-07-01

To describe the use of corneal collagen cross-linking (CXL) and its efficacy in the stabilization of keratorefractive procedures, including PRK, laser in-situ keratomileusis (LASIK), thermal keratoplasty, and orthokeratology. Since its introduction, CXL has quickly gained interest in the treatment of ectactic disorders due to its ability to increase the biomechanical stability of the cornea. In its earliest use, it has shown to be effective in the treatment of both keratoconus and post-LASIK ectasia. More recent studies of CXL in combination with keratorefractive procedures have shown varying degrees of success. CXL with PRK has shown to be effective in slowing or halting the progression of keratoconus, pellucid marginal degeneration, and post-LASIK ectasia, in addition to potentially decreasing or delaying the need for penetrating keratoplasty. Several small case series have also demonstrated improved stability and efficacy of PRK and LASIK when combined with CXL, as well as a potentially decreased risk of postprocedure ectasia. In conjunction with thermokeratoplasty and orthokeratology, CXL has shown improved but only temporary results in the treatment of keratoconus. Future studies are needed to determine the efficacy and long-term stability of CXL in combination with keratorefractive procedures, as well as to address possible complications.

Indicações para ceratoplastia penetrante no Hospital das Clínicas-UNICAMP Penetrating keratoplasty indications in "Hospital das Clínicas-UNICAMP"

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Vanessa Gonçalves Crespi Flores

2007-06-01

Full Text Available OBJETIVO: Determinar as principais causas de indicação de transplante penetrante no Hospital das Clínicas-UNICAMP no período de janeiro de 1999 a dezembro de 2003. MÉTODOS: Estudo de série de casos, retrospectivo, não comparativo. Os autores revisaram os prontuários de 857 pacientes submetidos à ceratoplastia penetrante no Hospital das Clínicas-UNICAMP entre 1999-2003 e os classificaram em categorias diagnósticas de indicação para cirurgia. RESULTADOS: Dentre os 857 prontuários revisados a idade variou de 0-88 anos (média 44 anos±1,2. Dentre as principais causas de indicação de transplante de córnea encontramos: ceratocone em 427 casos (49,82%; úlcera de córnea infecciosa perfurada ou não, 152 casos (17,74%; falência de transplante prévio, 87 casos (10,15%; ceratopatia bolhosa, 72 casos (8,40%; distrofia de Fuchs, 59 casos (6,88%; seqüela de tracoma, 28 casos (3,27%; outras causas, 32 casos (3,74%. Entre as crianças até 10 anos a principal causa de indicação de transplante foram as úlceras infecciosas (77,78% e entre 11-50 anos o ceratocone foi a principal causa (71,65%. CONCLUSÕES: Este estudo foi composto por uma população jovem e as principais causas de indicação de transplante foram o ceratocone e os transplantes tectônicos.PURPOSE: To determine the main causes of penetrating keratoplasty indications at "Hospital das Clínicas-UNICAMP" (January, 1999 to December, 2003. METHODS: A non-comparative, retrospective series of case studies. The authors reviewed the files of 857 patients who underwent penetrating keratoplasty at "Hospital das Clínicas-UNICAMP" between 1999-2003 and classified them into different categories according to diagnostic indication for surgery. RESULTS: The age range was between 0-88 years (average 44 years ±1.2. The main causes of penetrating keratoplasty were: keratoconus in 427 cases (49.82%; 152 cases (17.74% of corneal ulceration (perforated or not; corneal graft failure in 87

Customized photorefractive keratectomy to correct high ametropia after penetrating keratoplasty: A pilot study

OpenAIRE

De Rosa, Giuseppe; Boccia, Rosa; Santamaria, Carmine; Fabbozzi, Lorenzo; De Rosa, Luigi; Lanza, Michele

2014-01-01

Purpose: To evaluate preliminarily the safety and efficacy of customized photorefractive keratectomy (PRK) to correct ametropia and irregular astigmatism after penetrating keratoplasty (PK). Methods: This pilot study included five eyes of five patients with a mean spherical equivalent of −5.1 ± 1.46 D (range from −2.75 to −6.50 D). In all cases, ametropia and irregular astigmatism was corrected with topography-guided customized PRK. Ocular examinations with topographic analysis were perfor...

Delayed-Onset Post-Keratoplasty Endophthalmitis Caused by Vancomycin-Resistant Enterococcus faecium

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Julio C. Hernandez-Camarena

2012-10-01

Full Text Available Background: Vancomycin-resistant Enterococcus (VRE endophthalmitis after penetrating keratoplasty (PKP is very rare, the management is a challenge due to both the pattern of antibiotic resistance and the aggressive nature of the infectious process. We report the first delayed-onset case of VRE endophthalmitis after PKP. Materials and Methods: Case report of a 51-year-old female with a 7-week history of PKP who arrived at the emergency room with signs and symptoms of endophthalmitis. Initial visual acuity was light perception, and a posterior pole exam was not possible due to the intense vitreous reaction. Mode B ultrasound was used to assess the posterior pole. The patient underwent pars plana vitrectomy and received intravitreous antibiotics. Results: Vitreous stains and cultures were positive for Enterococcus faecium resistant to vancomycin. Donor rim cultures and viral PCR were negative. Treatment was carried out by repeated intravitreal antibiotics and systemic linezolid. Clinical improvement was seen after the second dose of intravitreous antibiotics and systemic linezolid, but visual acuity remained at light perception consistent with the ischemic changes observed in the posterior pole. Conclusion: VRE endophthalmitis might be associated with positive donor rim cultures. Prompt use of systemic linezolid in addition to intravitreous antibiotics is recommendable, but even with prompt treatment, visual prognosis is guarded.

Signaling hierarchy regulating human endothelial cell development.

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Kelly, Melissa A; Hirschi, Karen K

2009-05-01

Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

Non-pharmacological modification of endothelial function: An important lesson for clinical practice

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Monika Szulińska

2018-03-01

The impact of endothelial function in the complex pathology of cardiovascular diseases reflects a number of scientific proofs showing favorable effects of non-pharmacological interventions in endothelial dysfunction treatment.

Fuchs dystrophy

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... Lippincott Williams & Wilkins; 2013:vol 4, chap 16. Price MO, Price FW. Endothelial keratoplasty. In: Yanoff M, Duker JS, ... Learn more about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A. ...

Comparison of synthetic glues and 10-0 nylon in rabbit lamellar keratoplasty.

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Cho, Soon Young; Kim, Man Soo; Oh, Su Ja; Chung, Sung Kun

2013-09-01

To evaluate changes in mean keratometry and to compare wound repair with corneal lamellar grafts in rabbit eyes using human synthetic tissue adhesives and 10-0 nylon. Corneal grafts were made using a 6.0-mm-diameter trephine and blades in the eyes of 15 New Zealand white rabbits. Human fibrin tissue adhesive (Tisseel) was used in group 1, human fibrin tissue adhesive (Beriplast P) was used in group 2, polyethylene glycol adhesive (Coseal) was used in group 3, and 8 bite sutures with 10-0 nylon were used in group 4 (control) for lamellar keratoplasty. Four bite sutures were made with 10-0 nylon in groups 1, 2, and 3. Slit-lamp microscopy and keratometry were performed at 3 days and 1, 2, and 4 weeks after the surgery. Histopathologic and electromicroscopic examinations were performed 4 weeks after the surgery. No inflammation or corneal toxicity was seen in groups 1 and 2. Histologically, a few inflammatory cells were seen in groups 3 and 4. Groups 1, 2, and 3 showed no statistically significant changes in mean keratometry at 4 weeks postoperatively compared with preoperative mean keratometry (Wilcoxon signed-rank test, P = 0.178, 0.208, and 0.889, respectively). The control group showed significant changes in mean keratometry at 4 weeks postoperatively (Wilcoxon signed-rank test, P = 0.018). Human fibrin tissue adhesives were well tolerated in rabbit eyes, with no apparent corneal toxicity. Polyethylene glycol adhesive showed more inflammation and insufficient wound repair compared with human fibrin tissue adhesives. Therefore, human fibrin tissue adhesives can be used as an alternative to sutures in lamellar keratoplasty.

Endothelial RIG-I activation impairs endothelial function

International Nuclear Information System (INIS)

Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

2012-01-01

Highlights: ► RIG-I activation impairs endothelial function in vivo. ► RIG-I activation alters HCAEC biology in vitro. ► EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5′end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

Endothelial dysfunction in metabolic and vascular disorders.

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Polovina, Marija M; Potpara, Tatjana S

2014-03-01

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

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Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

2012-01-01

Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

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Alessandra Petrelli

2012-01-01

Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

Endothelial RIG-I activation impairs endothelial function

Energy Technology Data Exchange (ETDEWEB)

Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

2012-03-30

Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

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Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Clinical outcomes after combined Ahmed glaucoma valve implantation and penetrating keratoplasty or pars plana vitrectomy.

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Lee, Jin Young; Sung, Kyung Rim; Tchah, Hung Won; Yoon, Young Hee; Kim, June Gone; Kim, Myoung Joon; Kim, Jae Yong; Yun, Sung-Cheol; Lee, Joo Yong

2012-12-01

To evaluate whether a combination of penetrating keratoplasty (PKP) or pars plana vitrectomy (PPV) and Ahmed glaucoma valve (AGV) implantation affords a level of success similar to that of AGV implantation alone. Eighteen eyes underwent simultaneous PPV and AGV, 14 eyes with PKP and AGV and 30 eyes with AGV implantation alone were evaluated. Success was defined as attainment of an intraocular pressure (IOP) >5 and glaucoma medication. Kaplan-Meier survival analysis was performed to compare cumulative survival between the combined surgery groups and the AGV implantation-alone group. Cox proportional hazard regression analysis was conducted to identify factors predictive of success in each of the three groups. Mean (±standard deviation) preoperative IOP was 30.2 ± 10.2 mmHg in the PKP + AGV, 35.2 ± 9.8 mmHg in the PPV + AGV, and 36.2 ± 10.1 mmHg in the AGV implantation-alone group. The cumulative success rate at 18 months was 66.9%, 73.2%, and 70.8% in the three groups, respectively. Neither combined surgery group differed significantly in terms of cumulative success rate compared with the AGV implantation-alone group (p = 0.556, p = 0.487, respectively). The mean number of preoperative anti-glaucoma medications prescribed was significantly associated with success in the PKP + AGV implantation group (hazard ratio, 2.942; p = 0.024). Either PKP or PPV performed in conjunction with AGV implantation afforded similar success rates compared to patients treated with AGV implantation alone. Therefore, in patients with refractory glaucoma who have underlying corneal or retinal pathology requiring treatment with PKP or PPV, AGV implantation can be performed simultaneously.

Intraocular pressure measurements and corneal biomechanical properties using a dynamic Scheimpflug analyzer, after several keratoplasty techniques, versus normal eyes.

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Hugo, J; Granget, E; Ho Wang Yin, G; Sampo, M; Hoffart, L

2018-01-01

To evaluate the biomechanical properties of the cornea and their impact on intraocular pressure (IOP) measurement after lamellar keratoplasty, compared to healthy eyes, using a non-contact tonometer with a Scheimpflug camera. This study, from 2014 to 2015, included 22 primary DSAEK, 5 DALK, 6 DSAEK after PK, and 50 control eyes. Using a non-contact tonometer with a high-speed Scheimpflug camera (CORVIS ST, Oculus Optikgeräte GmbH, Wetzlar, Germany), several biomechanical parameters were recorded, including radius at highest concavity (R hc ) and defomation amplitude (DA). Central corneal thickness (CCT) and uncorrected IOP, were also recorded. For the control eyes only, a corrected IOP was calculated, based on age, central corneal thickness, and biomechanical parameters. R hc was significantly lower after DALK (R hc =5.54±0.71, P=0.007) and DSAEK (R hc =6.26±0.77, P=0.042) compared to control eyes (R hc =6.82±0.76). DA was higher after DALK and DSAEK, but not significantly (respectively 1.24±0.09 P=0.41 and 1.22±0.15, P=0.923) compared to normal eyes (1.18±0.15). Uncorrected IOP was not significantly different between post-keratoplasty and control eyes. In control eyes, the corrected IOP (15.23±1.88) was lower than the uncorrected IOP (16.10±2.34); a statistically significant positive correlation between R hc and CCT (R 2 =0.6020, P<0001), and a significant negative correlation between DA and CCT (R 2 =-0.641, P<0.0001) were found. Our study showed that, after lamellar keratoplasty, corneal biomechanics are altered. Corneas with higher ocular rigidity will show a lower DA and a higher R hc . Copyright © 2017 Elsevier Masson SAS. All rights reserved.

'Blue bubble' technique: an ab interno approach for Descemet separation in deep anterior lamellar keratoplasty using trypan blue stained viscoelastic device.

Science.gov (United States)

Livny, Eitan; Bahar, Irit; Hammel, Naama; Nahum, Yoav

2018-04-01

In this study, we examined a novel variant of 'big-bubble' deep anterior lamellar keratoplasty using trypan-blue-stained viscoelastic device for the creation of a pre-descemetic bubble. Ten corneoscleral rims were mounted on an artificial anterior chamber (AC). The AC was filled with air through a limbal paracentesis. A Melles' triangulated spatula was inserted through the paracentesis, with its tip penetrating the AC, was then slightly retracted and pushed into the deep stroma above the roof of the paracentesis. A mixture of trypan blue and viscoelastic device (Healon, Abbott Medical Optics, Abbott Park, Illinois) was injected into this intra-stromal pocket using a 27-G cannula to create a pre-descemetic separation bubble. Bubble type and visualization of dyed viscoelastic device were noted. The method was later employed in three cases. In all 10 corneoscleral rims, the technique successfully created a visible pre-descemetic (type 1) bubble that could be expanded up to the predicted diameter of trephination. Subsequent trephination and the removal of corneal stroma were uneventful. In two out of four clinical cases, a type 1 bubble was created, while in two others, visco-dissection failed and dyed viscoelastic was seen in the AC. The presented technique holds promise of being a relatively easy to perform, predictable and well-controlled alternative for achieving a type 1 bubble during deep anterior lamellar keratoplasty surgery. The trypan-blue-stained viscoelastic device facilitates proper visualization and control of the separation bubble and assists in identifying the penetrance to the separation bubble prior to removal of the stromal cap. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Endothelial cell preservation at hypothermic to normothermic conditions using clinical and experimental organ preservation solutions

NARCIS (Netherlands)

Post, Ivo C. J. H.; de Boon, Wadim M. I.; Heger, Michal; van Wijk, Albert C. W. A.; Kroon, Jeffrey; van Buul, Jaap D.; van Gulik, Thomas M.

2013-01-01

Endothelial barrier function is pivotal for the outcome of organ transplantation. Since hypothermic preservation (gold standard) is associated with cold-induced endothelial damage, endothelial barrier function may benefit from organ preservation at warmer temperatures. We therefore assessed

Sickle erythrocytes inhibit human endothelial cell DNA synthesis

International Nuclear Information System (INIS)

Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

1990-01-01

Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

Corneal perforation after conductive keratoplasty with previous refractive surgery.

Science.gov (United States)

Kymionis, George D; Titze, Patrik; Markomanolakis, Marinos M; Aslanides, Ioannis M; Pallikaris, Ioannis G

2003-12-01

A 56-year-old woman had conductive keratoplasty (CK) for residual hyperopia and astigmatism. Three years before the procedure, the patient had arcuate keratotomy, followed by laser in situ keratomileusis 2 years later for high astigmatism correction in both eyes. During CK, a corneal perforation occurred in the right eye; during the postoperative examination, an iris perforation and anterior subcapsule opacification were seen beneath the perforation site. The perforation was managed with a bandage contact lens and an antibiotic-steroid ointment; it had a negative Seidel sign by the third day. The surgery in the left eye was uneventful. Three months after the procedure, the uncorrected visual acuity was 20/32 and the best corrected visual acuity 20/20 in both eyes with a significant improvement in corneal topography. Care must be taken to prevent CK-treated spots from coinciding with areas in the corneal stroma that might have been altered by previous refractive procedures.

Update on the Management of High-Risk Penetrating Keratoplasty.

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Jabbehdari, Sayena; Rafii, Alireza Baradaran; Yazdanpanah, Ghasem; Hamrah, Pedram; Holland, Edward J; Djalilian, Ali R

2017-03-01

In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

Penetrating keratoplasty in eThekwini Health District 2011–2014

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Monawwar Khan

2015-07-01

Full Text Available Background: Penetrating keratoplasty (PK – corneal transplantation or full-thickness corneal graft remains the primary sight-restoring procedure for corneal blindness. South Africa is experiencing a shortage of donor corneas, resulting in long waiting times for a corneal transplant. A corneal graft protocol has been drawn up in the eThekwini Health District to triage prospective corneal graft recipients. Aim: To describe the clinical and demographic profiles of patients on the elective corneal graft waiting list, the waiting time for PK and the scoring system prioritisation process of corneal graft allocation. Setting: All patients on the elective corneal graft waiting list in the eThekwini Health District. Methods: An observational, descriptive cross-sectional study was conducted for a 3-year period between April 2011 and March 2014. Results: A total of 104 patients were on the elective corneal graft waiting list for PK during the study period. Only 20% (n = 21 of patients received a corneal graft during the 3-year period. Amongst those that received a corneal graft, the median waiting period was 280 days (interquartile range 143–520 days. The majority of patients on the waiting list (67% were younger than 41 years of age. The commonest indication for PK was keratoconus (64%. Patients with higher pro forma scores are more likely to receive a corneal graft when a donor cornea becomes available. Conclusion: With a shortage of donor corneas, very few patients receive a corneal graft. Educational programmes are vital to increase awareness of corneal blindness and the value of corneal donations.

Does exercise and the stress of clinical examination influence endothelial function in dogs with mitral regurgitation?

DEFF Research Database (Denmark)

Moesgaard, Sophia Gry; Pedersen, Henrik Duelund; Holte, Andreas

2005-01-01

in plasma NOx when the sample was taken in the clinic (12.46±10.45 vs. 20.58±8.23 µM NOx for clinic vs. home samples, P = 0.02).Another study evaluated whether plasma NOx was influenced by an increased level of activity in normal dogs. This study showed a tendency towards a decrease in plasma NOx during......Nitric oxide (NO) produced by endothelial cells plays a role in numerous processes in the body including vasodilation, platelet aggregation and leukocyte adhesion. The plasma concentration of NO, measured as the stable metabolites nitrate and nitrite - referred to as NOx, can be measured and used...

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

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Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

Visual outcomes after deep anterior lamellar keratoplasty using donor corneas without removal of Descemet membrane and endothelium

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Tatiana Moura Bastos Prazeres

Full Text Available ABSTRACT Purpose: The optical quality of the interface after deep anterior lamellar keratoplasty (DALK using the big-bubble technique has been shown to be excellent, leading to results comparable to penetrating keratoplasty. However, there is little in the literature with respect to the controversy surrounding the preparation of the donor cornea. The purpose of this study was to evaluate visual acuity (VA in patients with keratoconus who underwent DALK without removal of the donor graft endothelium. Methods: The records of 90 patients who underwent DALK without the removal of the Descemet membrane (DM and endothelium were retrospectively reviewed. Data collected included uncorrected VA (UCVA and spectacle-corrected VA (SCVA at 7, 30, 180 days, and 1 year postoperatively. Contact lens-corrected visual acuity (CLVA was evaluated after 1 year of the procedure. Results: UCVA was significantly better than preoperative values at 7 days (p<0.001, 30 days (p<0.001, 180 days (p<0.001, and 1 year (p<0.001 after surgery. The 1-year postoperative mean SCVA and CLVA also improved when compared with preoperative SCVA (p<0.001 for both. Conclusions: DALK utilizing donor corneas with attached Descemet membrane and endothelium results in satisfactory VA in patients with keratoconus.

Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes

DEFF Research Database (Denmark)

Bordbar, Aarash; Johansson, Pär I.; Paglia, Giuseppe

2016-01-01

shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODS: Twenty RBC units...... years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSION: The state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables....

Experimental lamellar keratoplasty in rabbits using microfibrilar cellulose membrane: clinical, morphological and immunohistochemical findings Ceratoplastia lamelar experimental em coelhos usando membrana microfibrilar de celulose: achados clínicos, morfológicos e imunoistoquímicos

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Luciana Riacciardi Macedo

2010-02-01

Full Text Available The clinical, histopathological and immunohistochemical features of the cornea were investigated in adult male New Zealand rabbits submitted to lamellar keratoplasty with microfibrillar cellulose membrane. Thirty animals were divided into five groups (n=6 and evaluated up to 60 days after surgery. Clinical examination revealed moderate manifestations of edema, blepharospasm and photophobia on the second day, which became mild or disappeared after the seventh day. This period was characterized clinically by repair of the corneal defect. Histopathological analysis showed the presence of a thin layer of squamous cells covering the damaged area as early as 7th day, accompanied by a mild infiltrate of polymorphonuclear cells. Blood vessels were observed in the epithelium after the 15th day, which had regressed by day 48. Ki67 antibody labeling showed an increase of proliferating cells in the epithelium by the 15th day and in the stroma by day 30. Remodeling and epithelial adhesion were observed during this period. Microfibrillar cellulose membrane (Bionext® used for lamellar keratoplasty was found to yield good results considering the good integration of the implant.Avaliaram-se aspectos clínicos, histopatógicos e imunoistoquímicos da córnes de coelhos da raça Nova Zelândia adultos e machos em ceratoplastias lamelares com membrana de celulose microfibrilar. Trinta animais distribuídos em cinco grupos (n=6 foram estudados por até 60 dias de pós-operatório. A avaliação clínica revelou manifestações moderadas de edema, blefaroespasmo e fotofobia ao segundo dia, evoluindo para formas discretas ou ausentes a partir do sétimo dia, período em que se observou, clinicamente, reparo do defeito corneal. A histopatologia revelou uma fina camada de células escamosas, recobrindo a área lesada já aos sete dias, com discreto infiltrado de células polimorfonucleares. Observaram-se vasos no epitélio a partir do 15o dia, com regressão ao 48o dia

Quantification of collagen ultrastructure after penetrating keratoplasty - implications for corneal biomechanics.

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Craig Boote

Full Text Available To quantify long-term changes in stromal collagen ultrastructure following penetrating keratoplasty (PK, and evaluate their possible implications for corneal biomechanics.A pair of 16 mm post-mortem corneo-scleral buttons was obtained from a patient receiving bilateral penetrating keratoplasty 12 (left/28 (right years previously. Small-angle x-ray scattering quantified collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm intervals along linear scans across the graft margin. Corresponding control data was collected from two corneo-scleral buttons with no history of refractive surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at 0.25 mm (horizontal×0.25 mm (vertical intervals across both PK specimens. Quantification of orientation changes in the graft margin were verified by equivalent analysis of data from a 13 year post-operative right PK specimen obtained from a second patient in a previous study, and comparison made with new and published data from normal corneas.Marked changes to normal fibril alignment, in favour of tangentially oriented collagen, were observed around the entire graft margin in all PK specimens. The total number of meridional fibrils in the wound margin was observed to decrease by up to 40%, with the number of tangentially oriented fibrils increasing by up to 46%. As a result, in some locations the number of fibrils aligned parallel to the wound outnumbered those spanning it by up to five times. Localised increases in fibril spacing and diameter, with an accompanying reduction in matrix order, were also evident.Abnormal collagen fibril size and spatial order within the PK graft margin are indicative of incomplete stromal wound remodelling and the long term persistence of fibrotic scar tissue. Lasting changes in collagen fibril orientation in and around PK wounds may alter corneal biomechanics and compromise the integrity of the graft-host interface in the long term.

Simultaneous topography-guided PRK followed by corneal collagen cross-linking after lamellar keratoplasty for keratoconus.

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Spadea, Leopoldo; Paroli, Marino

2012-01-01

The purpose of this paper is to report the results of using combined treatment of customized excimer laser-assisted photorefractive keratectomy (PRK) and prophylactic corneal collagen crosslinking (CXL) for residual refractive error in a group of patients who had previously undergone lamellar keratoplasty for keratoconus. The study included 14 eyes from 14 patients who had originally been treated for keratoconus in one eye by excimer laser-assisted lamellar keratoplasty (ELLK), and subsequently presented with residual ametropia (-6.11 D ± 2.48, range -2.50 to -9.50). After a mean 40.1 ± 12.4 months since ELLK they underwent combined simultaneous corneal regularization treatment with topographically guided transepithelial excimer laser PRK (central corneal regularization) and corneal CXL induced by riboflavin-ultraviolet A. After a mean 15 ± 6.5 (range 6-24) months, all eyes gained at least one Snellen line of uncorrected distance visual acuity (range 1-10). No patient lost lines of corrected distance visual acuity, and four patients gained three lines of corrected distance visual acuity. Mean manifest refractive spherical equivalent was -0.79 ± 2.09 (range +1 to -3.0) D, and topographic keratometric astigmatism was 5.02 ± 2.93 (range 0.8-8.9) D. All the corneas remained clear (haze PRK and corneal CXL provided safe and effective results in the management of corneal regularization for refractive purposes after ELLK for keratoconus.

New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

Science.gov (United States)

Koizumi, Noriko; Okumura, Naoki; Ueno, Morio; Kinoshita, Shigeru

2014-11-01

Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome

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Abramowicz Marc

2008-10-01

Full Text Available Abstract Harboyan syndrome is a degenerative corneal disorder defined as congenital hereditary endothelial dystrophy (CHED accompanied by progressive, postlingual sensorineural hearing loss. To date, 24 cases from 11 families of various origin (Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican have been reported. More than 50% of the reported cases have been associated with parental consanguinity. The ocular manifestations in Harboyan syndrome include diffuse bilateral corneal edema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. They are apparent at birth or within the neonatal period and are indistinguishable from those characteristic of the autosomal recessive CHED (CHED2. Hearing deficit in Harboyan is slowly progressive and typically found in patients 10–25 years old. There are no reported cases with prelinglual deafness, however, a significant hearing loss in children as young as 4 years old has been detected by audiometry, suggesting that hearing may be affected earlier, even at birth. Harboyan syndrome is caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13-p12, indicating that CHED2 and Harboyan syndrome are allelic disorders. A total of 62 different SLC4A11 mutations have been reported in 98 families (92 CHED2 and 6 Harboyan. All reported cases have been consistent with autosomal recessive transmission. Diagnosis is based on clinical criteria, detailed ophthalmological assessment and audiometry. A molecular confirmation of the clinical diagnosis is feasible. A variety of genetic, metabolic, developmental and acquired diseases presenting with clouding of the cornea should be considered in the differential diagnosis (Peters anomaly, sclerocornea, limbal dermoids, congenital glaucoma. Audiometry must be performed to differentiate Harboyan syndrome from CHED2. Autosomal recessive types of CHED (CHED2 and

Pseudomonas aeruginosa endophthalmitis after penetrating keratoplasty transmitted from the same donor to two recipients confirmed by pulsed-field gel electrophoresis.

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Oguido, Ana Paula Miyagusko Taba; Casella, Antonio Marcelo Barbante; Hofling-Lima, Ana Luisa; Pacheco, Sergio Arruda; Bispo, Paulo José Martins; Marques, Fernanda

2011-09-01

Two devastating cases of multidrug-resistant Pseudomonas aeruginosa endophthalmitis after keratoplasty as the result of transmission from the same donor were confirmed by pulsed-field gel electrophoresis. Strategies for preventing donor-to-host transmission, such as the use of antimicrobial agents of greater efficacy and better methods for detecting microorganisms in preservation medium, could minimize this type of transmission.

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

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M. Moerland

2012-01-01

Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%. Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9±1.4 and 1.8±0.3, resp., versus 1.8±0.5, P>0.05. The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08±0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline 0.49±0.92, 95% confidence interval −0.47 to 1.46. This suggests that at present the EndoPAT might not be suitable to assess (changes in endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice.

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

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Menha Swellam

2009-01-01

Full Text Available Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE. Authors determine the clinical diagnostic role for thrombomodulin (TM, plasminogen activator inhibitor-1 (PAI-1 as endothelial markers and C-reactive protein (CRP, and interlukin-6 (IL-6 as inflammatory markers when tested independently or in combinations.

Microscopia confocal en operados de queratoplastia perforante Confocal microscopy in patients operated from penetrating keratoplasty

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Zulema Gómez Castillo

2009-06-01

the characteristics of the corneal tissue in patients undergoing this type of transplantation through in vivo confocal microscopy. METHODS: A cross-sectional descriptive study was carried out in 40 eyes from 40 patients operated with penetrating keratoplasty in the Corneal Service of "Ramón Pando Ferrer" Cuban Institute of Ophthalmology from March 2006 to March 2007. A clinical ophthalmologic history was drafted, and they were all subjected to confocal microscopic examination of the corneal graft using confocal microscope CONFOSCAN 4. RESULTS: Pseuphakic bullosa keratopathy was the most common disease prior to surgery and was present in 77.5 % of patients. Corneal thickness decreased in 72.5 % of the operated patients. The epithelium was altered in 62.5 %. All of them presented with problems in the endotelial cellular form and size. Nervous plexuses were not observed in 82.5 % of patients. CONCLUSIONS: Confocal microscopy as a new science in the field of ophthalmology favors the follow-up of penetrating keratoplasty and allows preventing possible complications and assuring the success of surgery and the restoration of the refractive function of the cornea.

[Circulating endothelial cells: biomarkers for monitoring activity of antiangiogenic therapy].

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Farace, Françoise; Bidart, Jean-Michel

2007-07-01

Tumor vessel formation is largely dependent on the recruitment of endothelial cells. Rare in healthy individuals, circulating endothelial cells (CEC) are shed from vessel walls and enter the circulation reflecting endothelial damage or dysfunction. Increased numbers of CEC have been documented in different types of cancer. Recent studies have suggested the role for CEC in tumor angiogenesis, but whose presence could also reflect normal endothelium perturbation in cancer. Originating from the bone marrow rather than from vessel walls, endothelial progenitor cells (EPC) are mobilized following tissue ischemia and may be recruited to complement local angiogenesis supplied by existing endothelium. Recently, studies in mouse models suggest that the circulating fraction of endothelial progenitors (CEP) is involved in tumor angiogenesis but their contribution is less clear in humans. The detection of CEC and CEP is difficult and impeded by the rarity of these cells. They may have important clinical implication as novel biomarkers susceptible to predict more efficiently and rapidly the therapeutic response to anti-angiogenic treatments. However, a methodological consensus would be necessary in order to correctly evaluate the clinical interest of CEC and CEP in patients.

Protective effects of dark chocolate on endothelial function and diabetes.

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Grassi, Davide; Desideri, Giovambattista; Ferri, Claudio

2013-11-01

Relationship between cocoa consumption and cardiovascular disease, particularly focusing on clinical implications resulting from the beneficial effects of cocoa consumption on endothelial function and insulin resistance. This could be of clinical relevance and may suggest the mechanistic explanation for the reduced risk of cardiovascular events reported in the different studies after cocoa intake. Increasing evidence supports a protective effect of cocoa consumption against cardiovascular disease. Cocoa and flavonoids from cocoa have been described to improve endothelial function and insulin resistance. A proposed mechanism could be considered in the improvement of the endothelium-derived vasodilator nitric oxide by enhancing nitric oxide synthesis or by decreasing nitric oxide breakdown. The endothelium plays a pivotal role in the arterial homeostasis, and insulin resistance is the most important pathophysiological feature in various prediabetic and diabetic states. Reduced nitric oxide bioavailability with endothelial dysfunction is considered the earliest step in the pathogenesis of atherosclerosis. Further, insulin resistance could account, at least in part, for the endothelial dysfunction. Endothelial dysfunction has been considered an important and independent predictor of future development of cardiovascular risk and events. Cocoa and flavonoids from cocoa might positively modulate these mechanisms with a putative role in cardiovascular protection.

Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

Science.gov (United States)

Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

2017-01-01

Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

Science.gov (United States)

Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

2009-03-01

Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

Endothelial dysfunction in the early postoperative period after major colon cancer surgery

DEFF Research Database (Denmark)

Ekeloef, S; Larsen, M H H; Schou-Pedersen, A M V

2017-01-01

BACKGROUND: Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide...... was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine - nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial...... dysfunction and cardiovascular complications after non-cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT02344771....

Endothelial dysfunction in the early postoperative period after major colon cancer surgery

DEFF Research Database (Denmark)

Ekeløf, Sara; Larsen, Mikkel Hjordt; Schou-Pedersen, Anne Marie Voigt

2017-01-01

Background. Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide...... was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine – nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial...... dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registration. NCT02344771....

Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design.

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McCrea, Cindy E; Skulas-Ray, Ann C; Chow, Mosuk; West, Sheila G

2012-02-01

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

Simple clinical means of documenting increased pulmonary endothelial permeability to protein

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Mishkin, F.S.; Niden, A.; Kumar, A.; Thomas, A.; Reese, I.C.; Vasinrapee, P.

1987-02-20

The authors investigated a simple method that can be used at the bedside for documenting the net accumulation of albumin in the lung. The technique employs measurement with a computer-linked gamma camera of the activity ratio in an area of the right lung compared with the same-sized area in the heart at 20 minutes and three hours following intravenous injection of technetium Tc 99m albumin. They applied this measurement to three groups of patients: a control group and patients with roentgenographic evidence of edema classified according to clinically available criteria as either hydrostatic edema or permeability edema to see if they could document differences among these groups. In control patients this ratio did not increase by more than seven units between the 20-minute and three-hour measurements. Of 18 patients classified by other routine clinical means as having hydrostatic pulmonary edema, 89% showed no increase in lung albumin accumulation. In 29 patients with permeability edema associated with the so-called adult respiratory distress syndrome, 31% showed evidence of net pulmonary albumin accumulation. These findings suggest that some patients otherwise classified as having hydrostatic edema have concomitant permeability changes in the microvasculature and that permeability edema represents a spectrum of endothelial damage.

Simple clinical means of documenting increased pulmonary endothelial permeability to protein

International Nuclear Information System (INIS)

Mishkin, F.S.; Niden, A.; Kumar, A.; Thomas, A.; Reese, I.C.; Vasinrapee, P.

1987-01-01

The authors investigated a simple method that can be used at the bedside for documenting the net accumulation of albumin in the lung. The technique employs measurement with a computer-linked gamma camera of the activity ratio in an area of the right lung compared with the same-sized area in the heart at 20 minutes and three hours following intravenous injection of technetium Tc 99m albumin. They applied this measurement to three groups of patients: a control group and patients with roentgenographic evidence of edema classified according to clinically available criteria as either hydrostatic edema or permeability edema to see if they could document differences among these groups. In control patients this ratio did not increase by more than seven units between the 20-minute and three-hour measurements. Of 18 patients classified by other routine clinical means as having hydrostatic pulmonary edema, 89% showed no increase in lung albumin accumulation. In 29 patients with permeability edema associated with the so-called adult respiratory distress syndrome, 31% showed evidence of net pulmonary albumin accumulation. These findings suggest that some patients otherwise classified as having hydrostatic edema have concomitant permeability changes in the microvasculature and that permeability edema represents a spectrum of endothelial damage

Quantification of Collagen Ultrastructure after Penetrating Keratoplasty – Implications for Corneal Biomechanics

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Gardner, Steven J.; Kamma-Lorger, Christina S.; Hayes, Sally; Nielsen, Kim; Hjortdal, Jesper; Sorensen, Thomas; Terrill, Nicholas J.; Meek, Keith M.

2013-01-01

Purpose To quantify long-term changes in stromal collagen ultrastructure following penetrating keratoplasty (PK), and evaluate their possible implications for corneal biomechanics. Methods A pair of 16 mm post-mortem corneo-scleral buttons was obtained from a patient receiving bilateral penetrating keratoplasty 12 (left)/28 (right) years previously. Small-angle x-ray scattering quantified collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm intervals along linear scans across the graft margin. Corresponding control data was collected from two corneo-scleral buttons with no history of refractive surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at 0.25 mm (horizontal)×0.25 mm (vertical) intervals across both PK specimens. Quantification of orientation changes in the graft margin were verified by equivalent analysis of data from a 13 year post-operative right PK specimen obtained from a second patient in a previous study, and comparison made with new and published data from normal corneas. Results Marked changes to normal fibril alignment, in favour of tangentially oriented collagen, were observed around the entire graft margin in all PK specimens. The total number of meridional fibrils in the wound margin was observed to decrease by up to 40%, with the number of tangentially oriented fibrils increasing by up to 46%. As a result, in some locations the number of fibrils aligned parallel to the wound outnumbered those spanning it by up to five times. Localised increases in fibril spacing and diameter, with an accompanying reduction in matrix order, were also evident. Conclusions Abnormal collagen fibril size and spatial order within the PK graft margin are indicative of incomplete stromal wound remodelling and the long term persistence of fibrotic scar tissue. Lasting changes in collagen fibril orientation in and around PK wounds may alter corneal biomechanics and compromise the integrity of the graft-host interface in the

Fluorescent in situ hybridization (FISH) on corneal impression cytology specimens (CICS): study of epithelial cell survival after keratoplasty.

Science.gov (United States)

Catanese, Muriel; Popovici, Cornel; Proust, Hélène; Hoffart, Louis; Matonti, Frédéric; Cochereau, Isabelle; Conrath, John; Gabison, Eric E

2011-02-22

To assess corneal epithelial cell survival after keratoplasty. Corneal impression cytology (CIC) was performed on sex-mismatched corneal transplants. Fluorescent in situ hybridization (FISH) with sex chromosome-specific probes was performed to identify epithelial cell mosaicism and therefore allocate the donor or recipient origin of the cells. Twenty-four samples of corneal epithelial cells derived from 21 transplanted patients were analyzed. All patients received post-operative treatment using dexamethasone eye drops, with progressive tapering over 18 months, and nine patients also received 2% cyclosporine eye drops. Out of the 24 samples reaching quality criteria, sex mosaicism was found in 13, demonstrating the presence of donor-derived cells at the center of the graft for at least 211 days post keratoplasty. Kaplan-Meier analysis established a median survival of donor corneal epithelial cells of 385 days. Although not statistically significant, the disappearance of donor cells seemed to be delayed and the average number of persistent cells appeared to be greater when 2% cyclosporine was used topically as an additional immunosuppressive therapy. The combination of corneal impressions and FISH analysis is a valuable tool with negligible side effects to investigate the presence of epithelial cell mosaicism in sex-mismatched donor transplants. Epithelial cells survived at the center of the graft with a median survival of more than one year, suggesting slower epithelial turnover than previously described.

Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

Science.gov (United States)

Roquer, J; Segura, T; Serena, J; Castillo, J

2009-01-01

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (ARTICO study will increase the knowledge of patient outcome after ischemic stroke and may help to improve our ability to detect patients at high risk of stroke recurrence or major cardiovascular events. (c) 2009 S. Karger AG, Basel.

Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

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Rie Kawabe-Yako

Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

A case of recipient bed melt and wound dehiscence after penetrating keratoplasty and subconjunctival injection of bevacizumab.

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Bhasin, Purendra; Gujar, Prateek; Bhasin, Priyamvada

2012-11-01

We describe a case of recipient bed melt and wound dehiscence after uneventful penetrating keratoplasty and subconjunctival injection of bevacizumab. Three weeks postoperatively, the patient presented with limbal ischemia, recipient bed melt, and wound dehiscence corresponding to the area of bevacizumab injection. The melt was managed by application of cyanoacrylate glue along with bandage contact lens. Although the graft survived, there was a problem in re-epithelization. This case highlights the need for further studies to elucidate the therapeutic dose, side effects, and correct timing of using bevacizumab with respect to corneal transplant surgery.

Endothelial dysfunction: a comprehensive appraisal

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Vilariño Jorge O

2006-02-01

vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called "endothelium independent". The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. Laser-Doppler techniques are now starting to be used that also consider tissue perfusion. There is so much proof about endothelial dysfunction that it is reasonable to believe that there is diagnostic and prognostic value in its evaluation for the late outcome. There is no doubt that endothelial dysfunction contributes to the initiation and progression of atherosclerotic disease and could be considered an independent vascular risk factor. Although prolonged randomized clinical trials are needed for unequivocal evidence, the data already obtained allows the methods of evaluation of endothelial dysfunction to be considered useful in clinical practice and have overcome the experimental step, being non-invasive increases its value making it use full for follow-up of the progression of the disease and the effects of different treatments.

The influence of biomaterials on endothelial cell thrombogenicity

Science.gov (United States)

McGuigan, Alison P.; Sefton, Michael V.

2007-01-01

Driven by tissue engineering and regenerative medicine, endothelial cells are being used in combination with biomaterials in a number of applications for the purpose of improving blood compatibility and host integration. Endothelialized vascular grafts are beginning to be used clinically with some success in some centers, while endothelial seeding is being explored as a means of creating a vasculature within engineered tissues. The underlying assumption of this strategy is that when cultured on artificial biomaterials, a confluent layer of endothelial cells maintain their non-thrombogenic phenotype. In this review the existing knowledge base of endothelial cell thrombogenicity cultured on a number of different biomaterials is summarized. The importance of selecting appropriate endpoint measures that are most reflective of overall surface thrombogenicity is the focus of this review. Endothelial cells inhibit thrombosis through three interconnected regulatory systems (1) the coagulation cascade (2) the cellular components of the blood such as leukocytes and platelets and (3) the complement cascade, and also through effects on fibrinolysis and vascular tone, the latter which influences blood flow. Thus, in order to demonstrate the thromobgenic benefit of seeding a biomaterial with EC, the conditions under which EC surfaces are more likely to exhibit lower thrombogenicity than unseeded biomaterial surfaces need to be consistent with the experimental context. The endpoints selected should be appropriate for the dominant thrombotic process that occurs under the given experimental conditions. PMID:17316788

Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

Science.gov (United States)

Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

2011-01-01

Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

Science.gov (United States)

Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

2013-12-01

Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

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Benjamin A Nacev

Full Text Available Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA, an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50 dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

Science.gov (United States)

Nacev, Benjamin A; Liu, Jun O

2011-01-01

Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50) dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy

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Mehran, Reza; Nilsson, Monique; Khajavi, Mehrdad; Du, Zhiqiang; Cascone, Tina; Wu, Hua Kang; Cortes, Andrea; Xu, Li; Zurita, Amado; Schier, Robert; Riedel, Bernhard; El-Zein, Randa; Heymach, John V.

2014-01-01

Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. PMID:24626092

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

Science.gov (United States)

Salmon, Andrew H J; Satchell, Simon C

2012-03-01

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants.

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Calderón-Garcidueñas, L; Villarreal-Calderon, R; Valencia-Salazar, G; Henríquez-Roldán, C; Gutiérrez-Castrellón, P; Torres-Jardón, R; Osnaya-Brizuela, N; Romero, L; Torres-Jardón, R; Solt, A; Reed, W

2008-03-01

Mexico City children are chronically exposed to significant concentrations of air pollutants and exhibit chronic respiratory-tract inflammation. Epidemiological, controlled human exposures, laboratory-based animal models, and in vitro/in vivo studies have shown that inflammatory, endothelial dysfunction, and endothelial damage mediators are upregulated upon exposure to particulate matter (PM). Endothelial dysfunction is a critical event in cardiovascular disease. The focus of this work was to investigate whether exposure to ambient air pollution including PM(2.5) produces systemic inflammation and endothelial injury in healthy children. We measured markers of endothelial activation, and inflammatory mediators in 52 children age 8.6+/-0.1 yr, residents of Mexico City (n: 28) or of Polotitlán (n: 24), a city with low levels of pollutants. Mexico City children had significant increases in inflammatory mediators and vasoconstrictors, including tumor necrosis factor (TNF)alpha, prostaglandin (PG) E2, C-reactive protein, interleukin-1beta, and endothelin-1. There was a significant anti-inflammatory response, and a downregulation of vascular adhesion molecule-1, intercellular adhesion molecule-1 and -2, and selectins sE and sL. Results from linear regression found TNF a positively associated with 24- and 48-h cumulative levels of PM(2.5), while the 7-d PM(2.5) value was negatively associated with the numbers of white blood cells in peripheral blood in highly exposed children. Systemic subclinical inflammation, increased endothelin- 1, and significant downregulation of soluble adhesion molecules are seen in Mexico City children. Children chronically exposed to fine PM above the standard could be at risk of developing cardiovascular diseases, atherosclerosis, stroke, and other systemic effects later in life.

Endothelial function in postmenopausal women with nighttime systolic hypertension.

Science.gov (United States)

Routledge, Faye S; Hinderliter, Alan L; McFetridge-Durdle, Judith; Blumenthal, James A; Paine, Nicola J; Sherwood, Andrew

2015-08-01

Hypertension becomes more prevalent in women during their postmenopausal years. Nighttime systolic blood pressure (SBP) is especially predictive of adverse cardiac events, and the relationship between rising nighttime SBP and cardiovascular risk increases more rapidly in women compared with men. The reasons for the prognostic significance of nighttime SBP are not completely known but may involve vascular endothelial dysfunction. The purposes of this study were to examine the relationship between nighttime SBP and endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), and to determine whether postmenopausal women with nighttime hypertension (SBP ≥120 mm Hg) evidenced greater endothelial dysfunction compared with women with normal nighttime SBP. One hundred postmenopausal women (mean [SD] age, 65.8 [7.5] y; mean [SD] body mass index, 28.3 [4.7] kg/m; hypertension, 47%; coronary artery disease, 51%; mean [SD] clinic SBP, 137 [17] mm Hg; mean [SD] clinic diastolic blood pressure, 67 [11] mm Hg; nighttime hypertension, 34 women) underwent 24-hour ambulatory blood pressure monitoring, actigraphy, and brachial artery FMD assessment. Multivariate regression models showed that higher nighttime SBP and larger baseline artery diameter were inversely related to FMD. Nighttime SBP and baseline artery diameter accounted for 23% of the variance in FMD. After adjustment for baseline artery diameter, women with nighttime hypertension had lower mean (SD) FMD than women with normal nighttime SBP (2.95% [0.65%] vs 5.52% [0.46%], P = 0.002). Nighttime hypertension is associated with reduced endothelial function in postmenopausal women. Research examining the therapeutic benefits of nighttime hypertension treatment on endothelial function and future cardiovascular risk in postmenopausal women is warranted.

Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

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Parikumar P

2011-01-01

Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

DEFF Research Database (Denmark)

Falskov, Britt; Hermann, Thomas Steffen; Raunsø, Jakob

2011-01-01

Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial func...... function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.......Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial...

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

Endothelial cell oxidative stress and signal transduction

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ROCIO FONCEA

2000-01-01

Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

Three Cases of Organized Hematoma of the Maxillary Sinus: Clinical Features and Immunohistological Studies for Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor 2 Expressions

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Shoichiro Imayoshi

2015-01-01

Full Text Available Objectives. Organized hematoma (OH is a rare, nonneoplastic, hemorrhagic lesion causing mucosal swelling and bone thinning, mainly in the maxillary sinus. We aimed to clarify the clinical presentation and treatment of OH. Methods. Three cases of maxillary sinus OH and a literature review are presented. Results. Three men aged 16–40 years complained of nasal obstruction, frequent epistaxis, and/or headache. Clinical and radiological examinations revealed a maxillary sinus OH. They were cured in a piecemeal fashion via endoscopic middle meatal antrostomy. Furthermore, vascular endothelial growth factor and its receptor were expressed in the lesion. Conclusions. The pathogenesis of OH is unclear and it presents various histological and imaging findings; however, it is not difficult to rule out malignant tumors. Minimally invasive surgery such as endoscopic sinus surgery can cure it completely. Thus, it is important to determine the diagnosis using CT and MRI and to quickly provide surgical treatment.

Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis

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Garcia-Barros, Monica; Paris, Francois; Cordon-Cardo, Carlos; Lyden, David; Rafii, Shahin; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

2003-05-01

About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

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Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Femtosecond laser-assisted deep anterior lamellar keratoplasty in phototherapeutic keratectomy versus the big-bubble technique in keratoconus

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Jarbas Pereira de Macedo

2018-05-01

Full Text Available AIM: To compare the functional and anatomic results of femtosecond laser (FSL-assisted deep anterior lamellar keratoplasty (DALK associated with phototherapeutic keratectomy (PTK and FSL-assisted DALK performed using the big-bubble technique in keratoconus. METHODS: During the first phase of the study, an electron microscopy histopathology pilot study was conducted that included four unsuitable donor corneas divided into two groups: in FSL group, FSL lamellar cuts were performed on two corneas and in FSL+PTK group, PTK was performed at the stromal beds of two corneas after FSL lamellar cuts were made. During the second phase of the study, a randomized clinical trial was conducted that included two treatment groups of patients with keratoconus: group 1 (n=14 eyes underwent FSL-assisted DALK associated with PTK and group 2 (n=12 eyes underwent FSL-assisted DALK associated with the big-bubble technique. The main outcome measures were the postoperative visual acuity (VA and optical coherence tomography (OCT measurements, confocal microscopic findings, and contrast sensitivity. RESULTS: In the pilot study, histopathology showed a more regular stromal bed in the FSL+PTK group. In the clinical trial, group 1 had significantly worse best spectacle-corrected VA and contrast sensitivity (P<0.05 for both comparisons. The residual stromal bed measured by OCT was significantly (P<0.05 thicker in group 1. Confocal microscopy detected opacities only at the donor-receptor interface in group 1. CONCLUSION: Patients with keratoconus treated with FSL-assisted DALK performed using the big-bubble technique fare better than treated with FSL-assisted DALK associated with PTK.

Effect of fibrin glue on the biomechanical properties of human Descemet's membrane.

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Shyam S Chaurasia

Full Text Available BACKGROUND: Corneal transplantation has rapidly evolved from full-thickness penetrating keratoplasty (PK to selective tissue corneal transplantation, where only the diseased portions of the patient's corneal tissue are replaced with healthy donor tissue. Descemet's membrane endothelial keratoplasty (DMEK performed in patients with corneal endothelial dysfunction is one such example where only a single layer of endothelial cells with its basement membrane (10-15 µm in thickness, Descemet's membrane (DM is replaced. It is challenging to replace this membrane due to its intrinsic property to roll in an aqueous environment. The main objective of this study was to determine the effects of fibrin glue (FG on the biomechanical properties of DM using atomic force microscopy (AFM and relates these properties to membrane folding propensity. METHODOLOGY/PRINCIPAL FINDINGS: Fibrin glue was sprayed using the EasySpray applicator system, and the biomechanical properties of human DM were determined by AFM. We studied the changes in the "rolling up" tendency of DM by examining the changes in the elasticity and flexural rigidity after the application of FG. Surface topography was assessed using scanning electron microscopy (SEM and AFM imaging. Treatment with FG not only stabilized and stiffened DM but also led to a significant increase in hysteresis of the glue-treated membrane. In addition, flexural or bending rigidity values also increased in FG-treated membranes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that fibrin glue provides rigidity to the DM/endothelial cell complex that may aid in subsequent manipulation by maintaining tissue integrity.

Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane

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Chaurasia, Shyam S.; Champakalakshmi, Ravi; Li, Ang; Poh, Rebekah; Tan, Xiao Wei; Lakshminarayanan, Rajamani; Lim, Chwee T.; Tan, Donald T.; Mehta, Jodhbir S.

2012-01-01

Background Corneal transplantation has rapidly evolved from full-thickness penetrating keratoplasty (PK) to selective tissue corneal transplantation, where only the diseased portions of the patient's corneal tissue are replaced with healthy donor tissue. Descemet's membrane endothelial keratoplasty (DMEK) performed in patients with corneal endothelial dysfunction is one such example where only a single layer of endothelial cells with its basement membrane (10–15 µm in thickness), Descemet's membrane (DM) is replaced. It is challenging to replace this membrane due to its intrinsic property to roll in an aqueous environment. The main objective of this study was to determine the effects of fibrin glue (FG) on the biomechanical properties of DM using atomic force microscopy (AFM) and relates these properties to membrane folding propensity. Methodology/Principal Findings Fibrin glue was sprayed using the EasySpray applicator system, and the biomechanical properties of human DM were determined by AFM. We studied the changes in the “rolling up” tendency of DM by examining the changes in the elasticity and flexural rigidity after the application of FG. Surface topography was assessed using scanning electron microscopy (SEM) and AFM imaging. Treatment with FG not only stabilized and stiffened DM but also led to a significant increase in hysteresis of the glue-treated membrane. In addition, flexural or bending rigidity values also increased in FG-treated membranes. Conclusions/Significance Our results suggest that fibrin glue provides rigidity to the DM/endothelial cell complex that may aid in subsequent manipulation by maintaining tissue integrity. PMID:22662156

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

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Possomato-Vieira, José S.; Khalil, Raouf A.

2016-01-01

Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia. PMID:27451103

Endothelial progenitor cell-based neovascularization : implications for therapy

NARCIS (Netherlands)

Krenning, Guido; van Luyn, Marja J. A.; Harmsen, Martin C.

Ischemic cardiovascular events are a major cause of death globally. Endothelial progenitor cell (EPC)-based approaches can result in improvement of vascular perfusion and might offer clinical benefit. However, although functional improvement is observed, the lack of long-term engraftment of EPCs

[The status quo and expectation of corneal research in China].

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Shi, Weiyun; Xie, Lixin

2014-09-01

In China, corneal disease is currently the second leading cause of blindness. Severe donor shortage, insufficient technique supports and promotion, and the lack of corneal disease specialists due to poor systematic training are all urgent problems to be resolved. The last 5 years have witnessed a considerable progress in basic and clinical researches of corneal disease. Investigations on the pathogenesis and treatment of fungal keratitis have won an international reputation. Results from the study of corneal reconstruction with tissue-engineered and acellular matrix corneas have been tested in clinical trials with good preliminary performance. Moreover, the clinical researches of corneal refractive surgery have kept pace with the latest international progresses. However, Descemet's membrane endothelial keratoplasty needs further promotion, and the development and application of keratoprosthesis remains a blank. Although keratoprosthesis and corneal collagen cross-linking have been widely applied in Europe with satisfactory clinical efficacy, they are still under assessment by China Food and Drug Administration for approval of use.

[Opacification of an intraocular lens: calcification of hydrophilic intraocular lenses after gas tamponade of the anterior chamber].

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Schmidinger, G; Pemp, B; Werner, L

2013-11-01

A patient with endothelial dystrophy was treated with Descemet stripping automated endothelial keratoplasty (DSAEK) combined with cataract extraction and implantation of a hydrophilic intraocular lens (IOL, Lentis-L312, Oculentis) but visual acuity dropped from 0.15 logMAR to 0.52 logMAR 18 months later due to calcification of the IOL. With new methods of lamellar corneal transplantation being used more frequently the number of necessary anterior chamber tamponades with air/gas are increasing. In cataract cases in which a gas tamponade and transplantation might be necessary later on (cornea guttata), hydrophilic IOLs should be avoided.

Simvastatin Ameliorates Matrix Stiffness-Mediated Endothelial Monolayer Disruption.

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Marsha C Lampi

Full Text Available Arterial stiffening accompanies both aging and atherosclerosis, and age-related stiffening of the arterial intima increases RhoA activity and cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized the statin simvastatin could be used to attenuate RhoA activity and inhibit the deleterious effects of increased age-related matrix stiffness on endothelial barrier function. Using polyacrylamide gels with stiffnesses of 2.5, 5, and 10 kPa to mimic the physiological stiffness of young and aged arteries, endothelial cells were grown to confluence and treated with simvastatin. Our data indicate that RhoA and phosphorylated myosin light chain activity increase with matrix stiffness but are attenuated when treated with the statin. Increases in cell contractility, cell-cell junction size, and indirect measurements of intercellular tension that increase with matrix stiffness, and are correlated with matrix stiffness-dependent increases in monolayer permeability, also decrease with statin treatment. Furthermore, we report that simvastatin increases activated Rac1 levels that contribute to endothelial barrier enhancing cytoskeletal reorganization. Simvastatin, which is prescribed clinically due to its ability to lower cholesterol, alters the endothelial cell response to increased matrix stiffness to restore endothelial monolayer barrier function, and therefore, presents a possible therapeutic intervention to prevent atherogenesis initiated by age-related arterial stiffening.

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

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Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

2015-08-07

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

A fully automated cell segmentation and morphometric parameter system for quantifying corneal endothelial cell morphology.

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Al-Fahdawi, Shumoos; Qahwaji, Rami; Al-Waisy, Alaa S; Ipson, Stanley; Ferdousi, Maryam; Malik, Rayaz A; Brahma, Arun

2018-07-01

Corneal endothelial cell abnormalities may be associated with a number of corneal and systemic diseases. Damage to the endothelial cells can significantly affect corneal transparency by altering hydration of the corneal stroma, which can lead to irreversible endothelial cell pathology requiring corneal transplantation. To date, quantitative analysis of endothelial cell abnormalities has been manually performed by ophthalmologists using time consuming and highly subjective semi-automatic tools, which require an operator interaction. We developed and applied a fully-automated and real-time system, termed the Corneal Endothelium Analysis System (CEAS) for the segmentation and computation of endothelial cells in images of the human cornea obtained by in vivo corneal confocal microscopy. First, a Fast Fourier Transform (FFT) Band-pass filter is applied to reduce noise and enhance the image quality to make the cells more visible. Secondly, endothelial cell boundaries are detected using watershed transformations and Voronoi tessellations to accurately quantify the morphological parameters of the human corneal endothelial cells. The performance of the automated segmentation system was tested against manually traced ground-truth images based on a database consisting of 40 corneal confocal endothelial cell images in terms of segmentation accuracy and obtained clinical features. In addition, the robustness and efficiency of the proposed CEAS system were compared with manually obtained cell densities using a separate database of 40 images from controls (n = 11), obese subjects (n = 16) and patients with diabetes (n = 13). The Pearson correlation coefficient between automated and manual endothelial cell densities is 0.9 (p system, and the possibility of utilizing it in a real world clinical setting to enable rapid diagnosis and for patient follow-up, with an execution time of only 6 seconds per image. Copyright © 2018 Elsevier B.V. All rights reserved.

Potential of Food and Natural Products to Promote Endothelial and Vascular Health.

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Auger, Cyril; Said, Amissi; Nguyen, Phuong Nga; Chabert, Philippe; Idris-Khodja, Noureddine; Schini-Kerth, Valérie B

2016-07-01

Endothelial dysfunction is now well established as a pivotal early event in the development of major cardiovascular diseases including hypertension, atherosclerosis, and diabetes. The alteration of the endothelial function is often triggered by an imbalance between the endothelial formation of vasoprotective factors including nitric oxide (NO) and endothelium-dependent hyperpolarization, and an increased level of oxidative stress involving several prooxidant enzymes such as NADPH oxidase and, often also, the appearance of cyclooxygenase-derived vasoconstrictors. Preclinical studies have indicated that polyphenol-rich food and food-derived products such as grape-derived products, black and red berries, green and black teas and cocoa, and omega-3 fatty acids can trigger activating pathways in endothelial cells promoting an increased formation of nitric oxide and endothelium-dependent hyperpolarization. Moreover, intake of such food-derived products has been associated with the prevention and/or the improvement of an established endothelial dysfunction in several experimental models of cardiovascular diseases and in humans with cardiovascular diseases. This review will discuss both experimental and clinical evidences indicating that different types of food and natural products are able to promote endothelial and vascular health, as well as the underlying mechanisms.

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

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Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

2008-08-01

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

Olive Oil Supplements Ameliorate Endothelial Dysfunction Caused by Concentrated Ambient Particulate Matter Exposure in Healthy Human Volunteers

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Context: Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for clinical cardiovascular events and progression of atherosclerosis. Dietary supplements such as olive oil and fish oil have beneficial effects on endothelial function, and ther...

The endothelial αENaC contributes to vascular endothelial function in vivo

DEFF Research Database (Denmark)

Tarjus, Antoine; Maase, Martina; Jeggle, Pia

2017-01-01

The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldo......-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo....

Induced Pluripotent Stem Cell-Derived Endothelial Cells in Insulin Resistance and Metabolic Syndrome.

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Carcamo-Orive, Ivan; Huang, Ngan F; Quertermous, Thomas; Knowles, Joshua W

2017-11-01

Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. © 2017 American Heart Association, Inc.

Study of light scattering using C-Quant® in patients with Fuchs' endothelial dystrophy: A pilot study.

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Castaño-Martín, B; Gros-Otero, J; Martínez, J; Teus, M

2017-11-01

The purpose of this study was to determine the light scattering in patients with Fuchs' endothelial dystrophy without clinically significant corneal oedema, and evaluate its relationship with endothelial cell count, corneal thickness, and corneal biomechanical parameters. The values of light scattering were measured by C-Quant ® (Oculus Optikgeräte GmbH, Germany) in 32 eyes of 17 patients diagnosed with Fuchs' endothelial dystrophy without clinically significant corneal oedema. Corneal biomechanical properties were determined using ORA (ocular response) and Corvis ST ® (tonometry). A light scattering value outside the normal range was observed in 93.8% of eyes studied. No statistically significant association (P>.05) was found between the values of the measured light scattering by C-Quant ® and endothelial count, pachymetry, or corneal biomechanical properties. In this study, changes were found in the values of light scattering values of patients with corneal Fuchs' endothelial dystrophy. This change does not appear to correlate significantly with disease severity. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor.

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Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-01

Reactive oxygen species (ROS) superoxide anion (O(2)()) and hydrogen peroxide (H(2)O(2)) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H(2)O(2)-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H(2)O(2) in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O(2)() in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

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Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

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Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

2015-01-01

ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

Intravascular Papillary Endothelial Hyperplasia Associated with Venous Pool Arising in the Lower Lip: A Case Report

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Hisanobu Yonezawa

2009-01-01

Full Text Available Intravascular papillary endothelial hyperplasia is a benign nonneoplastic vascular lesion that consists of endothelial cells with abundant vascular tissue with papillary proliferation. An adult female had a painless growing dark red nodule on the left side of the lower lip and often touched and gnawed at it for more than 4 years. The lesion was a tender, smooth mass approximately 1 cm in diameter without discoloration reaction. Magnetic resonance imaging of the lesion showed specific findings. She was diagnosed clinically as having mimicked hemangioma, and the lesion was totally excised under local anesthesia. Histopathological examination revealed that papillary proliferated endothelial cells with venous pool, and the lesion was diagnosed as intravascular papillary endothelial hyperplasia associated with venous pool. There has been no recurrence for more than 1 year. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings.

Young endothelial cells revive aging blood.

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Chang, Vivian Y; Termini, Christina M; Chute, John P

2017-11-01

The hematopoietic system declines with age, resulting in decreased hematopoietic stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell depletion. Aging of the hematopoietic system is associated with an increased incidence of myeloid malignancies and a decline in adaptive immunity. Therefore, strategies to rejuvenate the hematopoietic system have important clinical implications. In this issue of the JCI, Poulos and colleagues demonstrate that infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted HSC self-renewal and restored immune cell content in aged mice. Additionally, delivery of young BM ECs along with HSCs following total body irradiation improved HSC engraftment and enhanced survival. These results suggest an important role for BM endothelial cells (ECs) in regulating hematopoietic aging and support further research to identify the rejuvenating factors elaborated by BM ECs that restore HSC function and the immune repertoire in aged mice.

Folic acid: a marker of endothelial function in type 2 diabetes?

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Arduino A Mangoni

2005-04-01

Full Text Available Arduino A Mangoni1, Roy A Sherwood2, Belinda Asonganyi2, Emma L Ouldred3, Stephen Thomas4, Stephen HD Jackson31Department of Clinical Pharmacology, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, SA, Australia; 2Clinical Biochemistry, King’s College Hospital, London, UK; 3Department of Health Care of the Elderly, Guy’s, King’s, and St Thomas’ School of Medicine, King’s College, London, UK; 4Department of Diabetic Medicine, King’s College Hospital, London, UKObjectives: Endothelial dysfunction is a common feature of type 2 diabetes. Recent studies suggest that the B-vitamin folic acid exerts direct beneficial effects on endothelial function, beyond the well known homocysteine lowering effects. Therefore, folic acid might represent a novel “biomarker” of endothelial function. We sought to determine whether plasma levels of folic acid determine endothelial-dependent vasodilation in patients with type 2 diabetes.Methods: Forearm arterial blood flow (FABF was measured at baseline and during intrabrachial infusion of the endothelial-dependent vasodilator acetylcholine (15 µg/min and the endothelial-independent vasodilator sodium nitroprusside (2 µg/min in 26 type 2 diabetic patients (age 56.5 ± 0.9 years, means ± SEM with no history of cardiovascular disease.Results: FABF ratio (ie, the ratio between the infused and control forearm FABF significantly increased during acetylcholine (1.10 ± 0.04 vs 1.52 ± 0.07, p < 0.001 and sodium nitroprusside (1.12 ± 0.11 vs 1.62 ± 0.06, p < 0.001 infusions. After correcting for age, gender, diabetes duration, smoking, hypertension, body mass index, microalbuminuria, glycated hemoglobin, low-density lipoprotein cholesterol, and homocysteine, multiple regression analysis showed that plasma folic acid concentration was the only independent determinant (p = 0.037, R2 = 0.22 of acetylcholine-mediated, but not sodium nitroprusside-mediated, vasodilatation

Effects of oat and wheat bread consumption on lipid profile, blood sugar, and endothelial function in hypercholesterolemic patients: A randomized controlled clinical trial.

Science.gov (United States)

Momenizadeh, Amir; Heidari, Ramin; Sadeghi, Masoumeh; Tabesh, Faezeh; Ekramzadeh, Maryam; Haghighatian, Zahra; Golshahi, Jafar; Baseri, Mehdi

2014-09-01

Increased lipid profile after each meal can disturb the endothelial function. The present study assessed the effects of bread supplemented with oat bran on serum lipids and endothelial dysfunction in patients with hypercholesterolemia. This clinical trial was conducted on 60 isolated hypercholesterolemic patients. The subjects were randomly allocated to either intervention (consuming at least five daily servings of oat bread with 6 g beta-glucan) or control (receiving at least five servings of wheat bread). Anthropometric indicators, fasting blood sugar and lipid profiles ere measured at baseline and after 6 weeks (in the end of the intervention). Endothelial function was assessed using flow-mediated dilation (FMD). Within the group and between group differences were investigated using paired t-test and Student's t-test, respectively. Oat bread consumption could significantly reduce total cholesterol (P = 0.029). A significant increase in baseline and after ischemia brachial artery diameters at the end of the study was seen. However, it did not have a significant effect on FMD (P = 0.825). In the control group, none of the measured indices had changed significantly at the end of the study. Finally, only the mean change of brachial artery diameter after ischemia and baseline brachial artery diameter were significantly higher in the intervention group than in the control group (P = 0.036 and P = 0.012 respectively). Oat bread with beta-glucan could successfully reduce cholesterol levels. Furthermore, in this study oat bread did not reduce FMD more than wheat bread. Since hypercholesterolemia is a proven risk factor for endothelial dysfunction, hypercholesterolemic patients can hence be advised to eat oat bread.

Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

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Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

2017-11-01

Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

[Transpalpebral tonometry with a digital tonometer in healthy eyes and after penetrating keratoplasty].

Science.gov (United States)

Amm, M; Hedderich, J

2005-01-01

The Goldmann applanation technique established itself as gold standard for clinical intraocular pressure (IOP) measurement. But the device measures by corneal touch and presupposes corneal conditions within a normal range. So precise determination of IOP is crucial in corneal disorders and after corneal surgery. This pilot study presents tonometry data of normal and postkeratoplasty eyes measured transpalpebrally with a digital tonometer in comparison to Goldmann tonometry. The TGDc-01 tonometer is based on a ballistic principle of measurement. IOP was measured in 50 healthy eyes (group 1) and 40 eyes after penetrating keratoplasty (group 2) first by the TGDc-01 and after 3 minutes by Goldmann tonometry (Haag-Streit). Subjective refraction, keratometry and ultrasonic pachymetry were performed in all eyes. The IOP measurements in the postkeratoplasty eyes were done when corneal epithelium was fully closed and only a medium suture edema could be observed. The Pearson's product-moment correlation was r=0,46 for group 1 and 0,65 for group 2. Using the concordance correlation coefficient the value showed a reproducibility index of r(c)=0,44 in group 1 and r(c)=0,60 in group 2. Following the Bland-Altman-analysis 58% of the cases in group 1 had a difference between the two instruments of maximum 3 mmHg. In group 2, 53,5% of the eyes showed an absolute difference between Goldmann and TDGc-01 of 3 mmHg or less. A transpalpebral measurement technique-avoiding corneal contact-seems to be an alternative choice in patients with corneal pathologies and after corneal surgery. The TGDc-01 tonometer provided mostly similar results compared to the Goldmann device, but with fluctuations. Keeping the deviations between the two methods in mind we recommend, however, the use of the transpalpebral approach only in combination with other techniques (palpation, indentation) to obtain enough reliability of IOP information in problem eyes.

The Role of Plasma Transfusion in Massive Bleeding: Protecting the Endothelial Glycocalyx?

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Stefano Barelli

2018-04-01

Full Text Available Massive hemorrhage is a leading cause of death worldwide. During the last decade several retrospective and some prospective clinical studies have suggested a beneficial effect of early plasma-based resuscitation on survival in trauma patients. The underlying mechanisms are unknown but appear to involve the ability of plasma to preserve the endothelial glycocalyx. In this mini-review, we summarize current knowledge on glycocalyx structure and function, and present data describing the impact of hemorrhagic shock and resuscitation fluids on glycocalyx. Animal studies show that hemorrhagic shock leads to glycocalyx shedding, endothelial inflammatory changes, and vascular hyper-permeability. In these animal models, plasma administration preserves glycocalyx integrity and functions better than resuscitation with crystalloids or colloids. In addition, we briefly present data on the possible plasma components responsible for these effects. The endothelial glycocalyx is increasingly recognized as a critical component for the physiological vasculo-endothelial function, which is destroyed in hemorrhagic shock. Interventions for preserving an intact glycocalyx shall improve survival of trauma patients.

Clinical correlates of common corneal neovascular diseases:a literature review

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Nizar Saleh Abdelfattah

2015-02-01

Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.

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Mo, Jiao; Yang, Renhua; Li, Fan; Zhang, Xiaochao; He, Bo; Zhang, Yue; Chen, Peng; Shen, Zhiqiang

2018-03-15

Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats. Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H 2 O 2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD). Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H 2 O 2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin. Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the

Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times.

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Fauser, Sascha; Muether, Philipp S

2016-11-01

To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea). Seven of 89 treatment-naïve nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 28±4 months. The treatment was switched to PRN aflibercept injections and patients were followed for another 15±2 months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT. The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34±5 (26-69) days for ranibizumab and 67±14 (49-89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6 weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re-activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept. The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6 weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST. NCT01213667, post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Urea immunoliposome inhibits human vascular endothelial cell proliferation for hemangioma treatment

Science.gov (United States)

2013-01-01

Background Urea injection has been used in hemangioma treatment as sclerotherapy. It shrinks vascular endothelial cells and induces degeneration, necrosis, and fibrosis. However, this treatment still has disadvantages, such as lacking targeting and difficulty in controlling the urea dosage. Thus, we designed a urea immunoliposome to improve the efficiency of treatment. Methods The urea liposome was prepared by reverse phase evaporation. Furthermore, the urea immunoliposome was generated by coupling the urea liposome with a vascular endothelial growth factor receptor (VEGFR) monoclonal antibody using the glutaraldehyde cross-linking method. The influence of the urea immunoliposome on cultured human hemangioma vascular endothelial cells was observed preliminarily. Results Urea immunoliposomes showed typical liposome morphology under a transmission electron microscope, with an encapsulation percentage of 54.4% and a coupling rate of 36.84% for anti-VEGFR. Treatment with the urea immunoliposome significantly inhibited the proliferation of hemangioma vascular endothelial cells (HVECs) in a time- and dose-dependent manner. Conclusions The urea immunoliposome that we developed distinctly and persistently inhibited the proliferation of HVECs and is expected to be used in clinical hemangioma treatment. PMID:24266957

Endothelial dysfunction after non-cardiac surgery

DEFF Research Database (Denmark)

Søndergaard, E S; Fonnes, S; Gögenur, I

2015-01-01

was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment...

Corneal endothelial morphology and central thickness in patients with type II diabetes mellitus

DEFF Research Database (Denmark)

Storr-Paulsen, Allan; Singh, Amardeep; Jeppesen, Helene

2014-01-01

size was based on a power calculation (power = 0.90; p = 0.05). The diabetic patients had on average more than four HbA1c tests performed (mean 4.1; range 2-14) with intervals of at least 3 months as a reflection of the long-term glycaemic status. The controls had no diabetes confirmed by two causal......PURPOSE: To investigate corneal endothelial cell density and morphology in type II diabetic and non-diabetic patients and to relate potential differences to the glycaemic status. METHODS: A prospective clinical study including 107 patients with type II diabetes and 128 non-diabetic patients. Sample...... blood tests. The endothelial cell density, the variation in endothelial cell size (CV), the percentage of hexagonal cells, and the central corneal thickness (CCT) were recorded. RESULTS: Type II diabetic subjects did not differ from the non-diabetic control subjects with regards to endothelial cell...

Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

Institute of Scientific and Technical Information of China (English)

Junru Wang; Marjan Boerma; Qiang Fu; Martin Hauer-Jensen

2007-01-01

This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major dose-limiting factor. Microvascular injury is a prominent feature of both early (inflammatory), as well as delayed (fibroproliferative) radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.

Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

International Nuclear Information System (INIS)

Lin, Ming-Chung; Chen, Chia-Ling; Yang, Tsan-Tzu; Choi, Pui-Ching; Hsing, Chung-Hsi; Lin, Chiou-Feng

2012-01-01

An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

Energy Technology Data Exchange (ETDEWEB)

Lin, Ming-Chung [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan (China); Chen, Chia-Ling [Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Yang, Tsan-Tzu; Choi, Pui-Ching [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan (China); Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin@mail.ncku.edu.tw [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

2012-12-01

An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-like cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase

Nutraceuticals in cardiovascular prevention: lessons from studies on endothelial function.

Science.gov (United States)

Zuchi, Cinzia; Ambrosio, Giuseppe; Lüscher, Thomas F; Landmesser, Ulf

2010-08-01

An "unhealthy" diet is considered as a main cause of increased atherosclerotic cardiovascular disease in the industrialized countries. There is a substantial interest in the potential cardiovascular protective effects of "nutraceuticals," that is food-derived substances that exert beneficial health effects. The correct understanding of cardiovascular effects of these compounds will have important implications for cardiovascular prevention strategies. Endothelial dysfunction is thought to play an important role in development and progression of atherosclerosis, and the characterization of the endothelial effects of several nutraceuticals may provide important insights into their potential role in cardiovascular prevention. At the same time, the analysis of the endothelial effects of nutraceuticals may also provide valuable insights into mechanisms of why certain nutraceuticals may not be effective in cardiovascular prevention, and it may aid in the identification of food-derived substances that may have detrimental cardiovascular effects. These findings further support the notion that nutraceuticals do need support from large clinical outcome trials with respect to their efficacy and safety profile for cardiovascular prevention, before their widespread use can be recommended. In fact, the term nutraceutical was coined to encourage an extensive and profound research activity in this field, and numerous large-scale clinical outcome trials to examine the effects of nutraceuticals on cardiovascular events have now been performed or are still ongoing. Whereas it is possible that single nutraceuticals may be effective in cardiovascular prevention, this field of research provides also valuable insights into which food components may be particularly important for cardiovascular prevention, to further advice the composition of a particularly healthy diet. The present review summarizes recent studies on the endothelial effects of several nutraceuticals, that have been

Endothelial nitric oxide synthase polymorphism G298T in ...

Indian Academy of Sciences (India)

Supplementary data: Endothelial nitric oxide synthase polymorphism G298T in association with oxidative DNA damage in coronary atherosclerosis. Rajesh G. Kumar, Mrudula K. Spurthi, Kishore G. Kumar, Sanjib K. Sahu and Surekha H. Rani. J. Genet. 91, 349–352. Table 1. The demographic and clinical data of the CHD ...

Effects of oat and wheat bread consumption on lipid profile, blood sugar, and endothelial function in hypercholesterolemic patients: A randomized controlled clinical trial

Directory of Open Access Journals (Sweden)

Amir Momenizadeh

2014-09-01

Full Text Available BACKGROUND: Increased lipid profile after each meal can disturb the endothelial function. The present study assessed the effects of bread supplemented with oat bran on serum lipids and endothelial dysfunction in patients with hypercholesterolemia. METHODS: This clinical trial was conducted on 60 isolated hypercholesterolemic patients. The subjects were randomly allocated to either intervention (consuming at least five daily servings of oat bread with 6 g beta-glucan or control (receiving at least five servings of wheat bread. Anthropometric indicators, fasting blood sugar and lipid profiles ere measured at baseline and after 6 weeks (in the end of the intervention. Endothelial function was assessed using flow-mediated dilation (FMD. Within the group and between group differences were investigated using paired t-test and Student’s t-test, respectively. RESULTS: Oat bread consumption could significantly reduce total cholesterol (P = 0.029. A significant increase in baseline and after ischemia brachial artery diameters at the end of the study was seen. However, it did not have a significant effect on FMD (P = 0.825. In the control group, none of the measured indices had changed significantly at the end of the study. Finally, only the mean change of brachial artery diameter after ischemia and baseline brachial artery diameter were significantly higher in the intervention group than in the control group (P = 0.036 and P = 0.012 respectively. CONCLUSION: Oat bread with beta-glucan could successfully reduce cholesterol levels. Furthermore, in this study oat bread did not reduce FMD more than wheat bread. Since hypercholesterolemia is a proven risk factor for endothelial dysfunction, hypercholesterolemic patients can hence be advised to eat oat bread.   Keywords: Bread, Diet, Flow-Mediated Dilation, Hypercholesterolemia 

Apoptosis of Endothelial Cells by 13-HPODE Contributes to Impairment of Endothelial Barrier Integrity

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Valerie E. Ryman

2016-01-01

Full Text Available Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis of Streptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1 metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE, can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE, is abundantly produced during vascular activation. However, the relative contribution of specific LA-derived metabolites on impairment of mammary endothelial integrity is unknown. Our hypothesis was that S. uberis-induced LA-derived 15-LOX-1 oxygenation products impair mammary endothelial barrier integrity by apoptosis. Exposure of bovine mammary endothelial cells (BMEC to S. uberis did not increase 15-LOX-1 LA metabolism. However, S. uberis challenge of bovine monocytes demonstrated that monocytes may be a significant source of both 13-HPODE and 13-HODE during mastitis. Exposure of BMEC to 13-HPODE, but not 13-HODE, significantly reduced endothelial barrier integrity and increased apoptosis. Changing oxidant status by coexposure to an antioxidant during 13-HPODE treatment prevented adverse effects of 13-HPODE, including amelioration of apoptosis. A better understanding of how the oxidant status of the vascular microenvironment impacts endothelial barrier properties could lead to more efficacious treatments for S. uberis mastitis.

Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.

Science.gov (United States)

Kuck, Jamie L; Bastarache, Julie A; Shaver, Ciara M; Fessel, Joshua P; Dikalov, Sergey I; May, James M; Ware, Lorraine B

2018-01-01

Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of 14 C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC. CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability. CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

International Nuclear Information System (INIS)

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

Increased endothelial cell-leukocyte interaction in murine schistosomiasis: possible priming of endothelial cells by the disease.

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Suellen D S Oliveira

Full Text Available BACKGROUND AND AIMS: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF. Nitric oxide (NO donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. CONCLUSION/SIGNIFICANCE: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially

Transcytosis Involvement in Transport System and Endothelial Permeability of Vascular Leakage during Dengue Virus Infection

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Chanettee Chanthick

2018-02-01

Full Text Available The major role of endothelial cells is to maintain homeostasis of vascular permeability and to preserve the integrity of vascular vessels to prevent fluid leakage. Properly functioning endothelial cells promote physiological balance and stability for blood circulation and fluid components. A monolayer of endothelial cells has the ability to regulate paracellular and transcellular pathways for transport proteins, solutes, and fluid. In addition to the paracellular pathway, the transcellular pathway is another route of endothelial permeability that mediates vascular permeability under physiologic conditions. The transcellular pathway was found to be associated with an assortment of disease pathogeneses. The clinical manifestation of severe dengue infection in humans is vascular leakage and hemorrhagic diatheses. This review explores and describes the transcellular pathway, which is an alternate route of vascular permeability during dengue infection that corresponds with the pathologic finding of intact tight junction. This pathway may be the route of albumin transport that causes endothelial dysfunction during dengue virus infection.

Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women

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Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

2015-01-01

Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3hypothyroidism had a significantly lower % Δ CBF Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ CAD Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ CBF Ach (estimated difference in % Δ CBF Ach [SE]: −16.79 [8.18]). Conclusions Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients. PMID:26224049

Photorefractive keratectomy for post-penetrating keratoplasty myopia and astigmatism.

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Bilgihan, K; Ozdek, S C; Akata, F; Hasanreisoğlu, B

2000-11-01

To determine the safety, effectiveness, and predictability of photorefractive keratectomy (PRK) for the correction of myopia and astigmatism after penetrating keratoplasty. Gazi University, Medical School, Department of Ophthalmology, Ankara, Turkey. Photorefractive keratectomy was performed in 16 eyes of 16 patients with postkeratoplasty myopia and astigmatism who were unable to wear glasses due to anisometropia and were contact lens intolerant. They were examined for uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and corneal transplant integrity before and after surgery. The mean follow-up after PRK was 26.0 months +/- 15.7 (SD) (range 12 to 63 months). The mean preoperative spherical equivalent refraction of -4.47 +/- 1.39 diopters (D) was -3.39 +/- 1.84 D (P >.05) at the last postoperative visit and the mean preoperative cylinder of -5.62 +/- 2.88 D was -3.23 +/- 1.70 D (P <.05); refractive regression correlated with the amount of ablation performed. The BSCVA decreased in 3 eyes (18.8%), and the UCVA decreased in 2 (12.5%). Six eyes (37.5%) had grade 2 to 3 haze, which resolved spontaneously in 4 eyes within a relatively long time but caused a decrease in BSCVA in 2 (12.5%). Two of the eyes (12.5%) had a rejection episode after PRK and were successfully treated with topical steroids. Photorefractive keratectomy to correct postkeratoplasty myopia and astigmatism appears to be less effective and less predictable than PRK for naturally occurring myopia and astigmatism. Corneal haze and refractive regression are more prevalent, and patient satisfaction is not good.

Plastic compressed collagen as a novel carrier for expanded human corneal endothelial cells for transplantation.

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Hannah J Levis

Full Text Available Current treatments for reversible blindness caused by corneal endothelial cell failure involve replacing the failed endothelium with donor tissue using a one donor-one recipient strategy. Due to the increasing pressure of a worldwide donor cornea shortage there has been considerable interest in developing alternative strategies to treat endothelial disorders using expanded cell replacement therapy. Protocols have been developed which allow successful expansion of endothelial cells in vitro but this approach requires a supporting material that would allow easy transfer of cells to the recipient. We describe the first use of plastic compressed collagen as a highly effective, novel carrier for human corneal endothelial cells. A human corneal endothelial cell line and primary human corneal endothelial cells retained their characteristic cobblestone morphology and expression of tight junction protein ZO-1 and pump protein Na+/K+ ATPase α1 after culture on collagen constructs for up to 14 days. Additionally, ultrastructural analysis suggested a well-integrated endothelial layer with tightly opposed cells and apical microvilli. Plastic compressed collagen is a superior biomaterial in terms of its speed and ease of production and its ability to be manipulated in a clinically relevant manner without breakage. This method provides expanded endothelial cells with a substrate that could be suitable for transplantation allowing one donor cornea to potentially treat multiple patients.

Moorfields technique of donor cornea mounting for femtosecond-assisted keratoplasty: use of viscoelastic in the artificial anterior chamber.

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Iovieno, Alfonso; Chowdhury, Vivek; Stevens, Julian D; Maurino, Vincenzo

2012-07-01

Appropriate mounting and cutting of the donor sclero-corneal cap is often cumbersome during femtosecond laser-assisted keratoplasty. The authors describe a technique for donor cornea femtosecond laser cutting using ophthalmic viscoelastic devices. The donor sclero-corneal cap is mounted on the artificial anterior chamber using a dispersive ophthalmic viscoelastic device instead of saline solution. The chances of artificial anterior chamber pressure loss, inadequate applanation, and fluid leaks are consistently reduced with the use of dispersive ophthalmic viscoelastic devices. The speed of donor femtosecond laser cutting is increased. The viscosity and elasticity of dispersive ophthalmic viscoelastic devices greatly assist the procedure with regard to ease of applanation, corneal endothelium protection, and decreased distortion of the applanated cornea. Copyright 2012, SLACK Incorporated.

Endothelial microparticles (EMP in physiology and pathology

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Ewa Sierko

2015-08-01

Full Text Available Endothelial microparticles (EMP are released from endothelial cells (ECs in the process of activation and/or apoptosis. They harbor adhesive molecules, enzymes, receptors and cytoplasmic structures and express a wide range of various constitutive antigens, typical for ECs, at their surface. Under physiological conditions the concentration of EMP in the blood is clinically insignificant. However, it was reported that under pathological conditions EMP concentration in the blood might slightly increase and contribute to blood coagulation, angiogenesis and inflammation. It has been shown that EMP directly and indirectly contribute to the activation of blood coagulation. Endothelial microparticles directly participate in blood coagulation through their surface tissue factor (TF – a major initiator of blood coagulation. Furthermore, EMP exhibit procoagulant potential via expression of negatively charged phospholipids at their surface, which may promote assembly of coagulation enzymes (TF/VII, tenases and prothrombinase complexes, leading to thrombus formation. In addition, they provide a binding surface for coagulation factors: IXa, VIII, Va and IIa. Moreover, it is possible that EMP transfer TF from TF-bearing EMP to activated platelets and monocytes by binding them through adhesion molecules. Also, EMP express von Willebrand factor, which may facilitate platelet aggregation. Apart from their procoagulant properties, it was demonstrated that EMP may express adhesive molecules and metalloproteinases (MMP-2, MMP-9 at their surface and release growth factors, which may contribute to angiogenesis. Additionally, surface presence of C3 and C4 – components of the classical pathway – suggests pro-inflammatory properties of these structures. This article contains a summary of available data on the biology and pathophysiology of endothelial microparticles and their potential role in blood coagulation, angiogenesis and inflammation.

The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-5′-Nucleotidase (CD73) Release

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Kim, Mihwa; Ham, Ahrom; Kim, Katelyn Yu-Mi; Brown, Kevin M.; Lee, H. Thomas

2014-01-01

Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation. PMID:24945528

Circulating endothelial progenitor cells: a new approach to anti-aging medicine?

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Patel Amit N

2009-12-01

Full Text Available Abstract Endothelial dysfunction is associated with major causes of morbidity and mortality, as well as numerous age-related conditions. The possibility of preserving or even rejuvenating endothelial function offers a potent means of preventing/treating some of the most fearful aspects of aging such as loss of mental, cardiovascular, and sexual function. Endothelial precursor cells (EPC provide a continual source of replenishment for damaged or senescent blood vessels. In this review we discuss the biological relevance of circulating EPC in a variety of pathologies in order to build the case that these cells act as an endogenous mechanism of regeneration. Factors controlling EPC mobilization, migration, and function, as well as therapeutic interventions based on mobilization of EPC will be reviewed. We conclude by discussing several clinically-relevant approaches to EPC mobilization and provide preliminary data on a food supplement, Stem-Kine, which enhanced EPC mobilization in human subjects.

Evaluation of the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients: A randomized clinical trial

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Mohammad Hashemi

2016-01-01

Full Text Available Background: Pre-eclampsia as a hypertensive disorder of pregnancy complicates up to 5–10% of pregnancies worldwide. Endothelial dysfunction plays an important role in the pathogenesis of pre-eclampsia. In this study, we aim to evaluate the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients. Materials and Methods: In this triple-blinded randomized clinical trial, the enrolled patients were divided randomly into two groups. Folic acid 5.0 mg or placebo was taken daily by oral administration from the initiation of diagnosis until 2 months after delivery by the participants. Every patient's flow-mediated dilation (FMD was evaluated at the beginning of the study and 2 months after delivery with the same experienced operator at the same period of time (3–5 p.m. by high-resolution B-mode ultrasonography. Potential confounding variables were included in the independent samples t-test. t-test or Mann–Whitney U-test was used in the comparison of means between the intervention and placebo groups. To compare FMD in each group, before and after the intervention, paired t-test was used. Results: Mean value of FMD in intervention (9.64 ± 5.57 and control group (9.30 ± 4.25 has no significant difference before the consumption of drugs (P < 0.05. FMD in intervention group (13.72 ± 7.89 significantly increases after daily consumption of 5 mg folic acid in comparison with control group (10.02 ± 4.81 after daily consumption of placebo (P = 0.002. Conclusion: Increased mean of FMD in intervention group shows that this supplement can improve endothelial function and can be significantly affected by maternal blood pressure during pregnancy and some endothelium-dependent disease such as pre-eclampsia and its associated adverse outcomes.

Endothelial lipase is a major determinant of HDL level

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Ishida, Tatsuro; Choi, Sungshin; Kundu, Ramendra K.; Hirata, Ken-Ichi; Rubin, Edward M.; Cooper, Allen D.; Quertermous, Thomas

2003-01-30

For the past three decades, epidemiologic studies have consistently demonstrated an inverse relationship between plasma HDL cholesterol (HDL-C) concentrations and coronary heart disease (CHD). Population-based studies have provided compelling evidence that low HDL-C levels are a risk factor for CHD, and several clinical interventions that increased plasma levels of HDL-C were associated with a reduction in CHD risk. These findings have stimulated extensive investigation into the determinants of plasma HDL-C levels. Turnover studies using radiolabeled apolipoprotein A-I, the major protein component of HDL, suggest that plasma HDL-C concentrations are highly correlated with the rate of clearance of apolipoprotein AI. However, the metabolic mechanisms by which HDL are catabolized have not been fully defined. Previous studies in humans with genetic deficiency of cholesteryl ester transfer protein, and in mice lacking the scavenger receptor BI (SR-BI), have demonstrated that these proteins participate in the removal of cholesterol from HDL, while observations in individuals with mutations in hepatic lipase indicate that this enzyme hydrolyzes HDL triglycerides. In this issue of the JCI, reports from laboratories of Tom Quertermous and Dan Rader now indicate that endothelial lipase (LIPG), a newly identified member of the lipase family, catalyzes the hydrolysis of HDL phospholipids and facilitates the clearance of HDL from the circulation. Endothelial lipase was initially cloned by both of these laboratories using entirely different strategies. Quertermous and his colleagues identified endothelial lipase as a transcript that was upregulated in cultured human umbilical vein endothelial cells undergoing tube formation, whereas the Rader group cloned endothelial lipase as a transcript that was upregulated in the human macrophage-like cell line THP-1 exposed to oxidized LDL. Database searches revealed that endothelial lipase shows strong sequence similarity to lipoprotein

Reduced Ang2 expression in aging endothelial cells

International Nuclear Information System (INIS)

Hohensinner, P.J.; Ebenbauer, B.; Kaun, C.; Maurer, G.; Huber, K.; Wojta, J.

2016-01-01

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

Reduced Ang2 expression in aging endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

2016-06-03

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

Trifluoperazine: corneal endothelial phototoxicity

International Nuclear Information System (INIS)

Hull, D.S.; Csukas, S.; Green, K.

1983-01-01

Trifluoperazine is used for the treatment of psychiatric disorders. Perfusion of corneal endothelial cells with trifluoperazine-HC1 concurrent with exposure to long wavelength ultraviolet light resulted in a corneal swelling rate greater than that found in perfused corneas not exposed to ultraviolet light. Exposure of endothelial cells to 25 W incandescent light during perfusion with trifluoperazine-HC1 did not result in a higher corneal swelling rate compared to those perfused in the dark. The increased corneal swelling rate could be produced by pre-exposure of the trifluoperazine-HC1 perfusing solution to ultraviolet light suggesting the production of toxic photoproducts during exposure of trifluoperazine-HC1 to ultraviolet light. Perfusion of corneal endothelial cells with non-ultraviolet illuminated trifluoperazine-HC1 had no effect on endothelial cell membranes or ultrastructure. This is in contrast to cells perfused with trifluoperazine-HC1 that had been exposed to ultraviolet light in which there was an alteration of mitochondria and a loss of cytoplasmic homogeneity. The data imply that the trifluoperazine-HC1 photoproduct had an adverse effect on cellular transport mechanisms. The study also further demonstrates the value of the corneal endothelial cell model for identifying the physiological and anatomical changes occuring in photo-induced toxic reactions. (author)

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

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Kamei, Naosuke; Atesok, Kivanc; Ochi, Mitsuo

2017-01-01

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regenera...

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

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Muñoz-Hernandez, Rocio; Vallejo-Vaz, Antonio J; Sanchez Armengol, Angeles; Moreno-Luna, Rafael; Caballero-Eraso, Candela; Macher, Hada C; Villar, Jose; Merino, Ana M; Castell, Javier; Capote, Francisco; Stiefel, Pablo

2015-01-01

This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Observational study, before and after CPAP therapy. We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, pDNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

Radiation Effects on the Cytoskeleton of Endothelial Cells and Endothelial Monolayer Permeability

International Nuclear Information System (INIS)

Gabrys, Dorota; Greco, Olga; Patel, Gaurang; Prise, Kevin M.; Tozer, Gillian M.; Kanthou, Chryso

2007-01-01

Purpose: To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation. Methods and Materials: Cultured endothelial cells were X-ray irradiated, and actin filaments, microtubules, intermediate filaments, and vascular endothelial (VE)-cadherin junctions were examined by immunofluorescence. Permeability was determined by the passage of fluorescent dextran through cell monolayers. Signal transduction pathways were analyzed using RhoA, Rho kinase, and stress-activated protein kinase-p38 (SAPK2/p38) inhibitors by guanosine triphosphate-RhoA activation assay and transfection with RhoAT19N. The levels of junction protein expression and phosphorylation of myosin light chain and SAPK2/p38 were assessed by Western blotting. The radiation effects on cell death were verified by clonogenic assays. Results: Radiation induced rapid and persistent actin stress fiber formation and redistribution of VE-cadherin junctions in microvascular, but not umbilical vein endothelial cells, and microtubules and intermediate filaments remained unaffected. Radiation also caused a rapid and persistent increase in microvascular permeability. RhoA-guanosine triphosphatase and Rho kinase were activated by radiation and caused phosphorylation of downstream myosin light chain and the observed cytoskeletal and permeability changes. SAPK2/p38 was activated by radiation but did not influence either the cytoskeleton or permeability. Conclusion: This study is the first to show rapid activation of the RhoA/Rho kinase by radiation in endothelial cells and has demonstrated a link between this pathway and cytoskeletal remodeling and permeability. The results also suggest that the RhoA pathway might be a useful target for modulating the permeability and other effects of radiation for therapeutic gain

The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

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Murat Ziyrek

2015-12-01

Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

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Johansen, Maria E; Johansson, Pär I.; Ostrowski, Sisse R

2015-01-01

levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. organ failure and death in septic......Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively......), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels...

Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

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Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

2015-05-27

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

Regular consumption of vitamin D-fortified yogurt drink (Doogh improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

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Shab-Bidar Sakineh

2011-11-01

Full Text Available Abstract Background Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D. In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated. Methods Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50 or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50 twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP-9 were evaluated at the beginning and after the 12-week intervention period. Results The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI, glycated hemoglobin (HbA1c, triacylglycerols, high-density lipoprotein cholesterol (HDL-C, endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P P = 0.009 and P = 0.005, respectively but disappeared for E-selectin (P = 0.092. On the contrary, after controlling for serum 25(OHD, the differences disappeared for endothelin-1(P = 0.066 and MMP-9 (P = 0.277 but still remained significant for E-selectin (P = 0.011. Conclusions Ameliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers. Trial registration

LASIK hipermetrópico pós-DSAEK (Descement Stripping Automated Endotelial Keratoplasty

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Antonio Carlos Manhas Meireles

Full Text Available RESUMO O DSAEK (Descemet stripping automated endotelial Keratoplasty é um dos procedimentos de escolha para tratamento das doenças que acometem o endotélio corneano. Apesar do sucesso terapêutico, o procedimento pode induzir uma hipermetropia residual. Em média a refração se estabiliza em um perído que varia de 6 a 12 meses após o transplante. O objetivo desse relato é descrever a evolução dessa opção terapêutica utilizada em um paciente de 54 anos portador de Distrofia de Fuchs. O paciente foi submetido ao transplante de córnea (DSAEK e a remoção do cristalino no mesmo tempo cirúrgico o que resultou em hipermetropia residual. Após 3 anos de acompanhamento apresentava-se com a melhor visão corrigida de 20/20 (Snellen no olho operado com uma refração de +3,25 -1,00 (5º. Optou-se por realização de LASIK (Laser assisted in situ Keratomileusis hipermetrópico, obtendo um resultado visual satisfatório.

Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

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Christos Rammos

Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

Alterations in triglyceride rich lipoproteins are related to endothelial dysfunction in metabolic syndrome.

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Lucero, Diego; López, Graciela I; Gorzalczany, Susana; Duarte, Mariano; González Ballerga, Esteban; Sordá, Juan; Schreier, Laura; Zago, Valeria

2016-08-01

Our aim was to analyze the effect of circulating triglyceride rich lipoprotein (TRL) on endothelial function in metabolic syndrome (MetS). We studied 40 patients with MetS (ATPIII), divided into those presenting normal endothelial function (n=19) and those with endothelial dysfunction (n=21) by means of the evaluation of pulse wave velocity, before and after brachial artery ischemia. In fasting serum we measured lipid and lipoprotein profile, insulin and glucose (HOMA-IR). Moreover, isolated TRL (d<1006g/l) were chemically characterized. In parallel, using randomly selected TRL from MetS patients with endothelial dysfunction (n=6) and MetS patients with normal endothelial function (n=6), the ability of TRL to inhibit ACh-induced vasorelaxation (10(-9)-10(-5)mM) on aortic rings previously pre-contracted by noradrenaline (10(-8)mM) was evaluated. Interestingly, TRL isolated from MetS patients presenting endothelial dysfunction showed triglyceride over-enrichment (59.1±4.8 vs. 54.1±4.7%; p=0.04), even after adjusting by potential confounders (p=0.05). In addition, while TRL resulting from both MetS groups significantly inhibited endothelium dependent vasorelaxation (p<0.001), TRL from MetS patients with endothelial dysfunction showed a strong tendency to a greater inhibition of vasorelaxation (p=0.06). Moreover, TRL-triglyceride (%) showed a strong tendency to correlate with the grade of vasorelaxation inhibition exerted by TRL (r=0.60; p=0.05). These results, taken together, would allow inferring for the first time that the predominance of triglyceride over-enriched TRL in circulation in MetS would induce endothelial dysfunction, contributing to the inherent cardiovascular risk of MetS. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

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Rocio Muñoz-Hernandez

Full Text Available This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA syndrome at baseline and after three months with CPAP therapy.Observational study, before and after CPAP therapy.We studied 30 patients with apnoea/hypopnoea index (AHI >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA and microparticles (MPs were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF was determined as a marker of endothelial restoration process.After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005 cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05. These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005 but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together.CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

Physalis minima Leaves Extract Induces Re-Endothelialization in Deoxycorticosterone Acetate-Salt-Induced Endothelial Dysfunction in Rats

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Dian Nugrahenny

2018-02-01

Full Text Available The administration of deoxy-corticosterone acetate (DOCA-salt can induce oxidative stress leading to decrease the bioavailability of nitric oxide (NO, increase senescence of circulating endothelial progenitor cells (EPCs, thus contributing to endothelial dysfunction. This study was aimed to investigate the effects of Physalis minima L. leaves extract on serum NO levels, circulating EPCs number, and histopathology of tail artery endothelial cells in DOCA-salt-induced endothelial dysfunction in rats. Twenty-five male Wistar rats were randomly divided into five groups: rats without any treatment (normal, rats treated with DOCA (10 mg/kgBW s.c. twice weekly and given 0.9% NaCl to drink ad libitum for 6 weeks, and DOCA-salt-induced rats orally supplemented with P. minima leaves extract at doses of 500, 1500, or 2500 mg/kgBW for 4 weeks. Serum NO levels were measured by colorimetry. The number of circulating EPCs (CD34+/CD133+ cells was determined by flow cytometry. The tail artery sections were histologically processed with hematoxylin-eosin staining. DOCA-salt-induced rats showed significantly (p<0.05 decrease in serum NO levels and circulating EPCs number compared to the normal. There was also more detached tail artery endothelial cells in DOCA-salt-induced rats. P. minima leaves extract at a dose of 500 mg/kgBW significantly (p<0.05 increased serum NO level and circulating EPCs number, and also induced an optimal re-endothelialization in DOCA-salt-induced rats. P. minima leave extract dose-dependently increases NO bioavailability contributing to enhanced EPCs mobilization, thereby promoting re-endothelialization in DOCA-salt-induced endothelial dysfunction in rats.

Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

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Alexopoulou, Annika N; Ho-Yen, Colan M; Papalazarou, Vassilis; Elia, George; Jones, J Louise; Hodivala-Dilke, Kairbaan

2014-01-01

Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF.

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Schini-Kerth, Valérie B; Auger, Cyril; Kim, Jong-Hun; Etienne-Selloum, Nelly; Chataigneau, Thierry

2010-05-01

Numerous studies indicate that regular intake of polyphenol-rich beverages (red wine and tea) and foods (chocolate, fruit, and vegetables) is associated with a protective effect on the cardiovascular system in humans and animals. Beyond the well-known antioxidant properties of polyphenols, several other mechanisms have been shown to contribute to their beneficial cardiovascular effects. Indeed, both experimental and clinical studies indicate that polyphenols improve the ability of endothelial cells to control vascular tone. Experiments with isolated arteries have shown that polyphenols cause nitric oxide (NO)-mediated endothelium-dependent relaxations and increase the endothelial formation of NO. The polyphenol-induced NO formation is due to the redox-sensitive activation of the phosphatidylinositol3-kinase/Akt pathway leading to endothelial NO synthase (eNOS) activation subsequent to its phosphorylation on Ser 1177. Besides the phosphatidylinositol3-kinase/Akt pathway, polyphenols have also been shown to activate eNOS by increasing the intracellular free calcium concentration and by activating estrogen receptors in endothelial cells. In addition to causing a rapid and sustained activation of eNOS by phosphorylation, polyphenols can increase the expression level of eNOS in endothelial cells leading to an increased formation of NO. Moreover, the polyphenol-induced endothelium-dependent relaxation also involves endothelium-derived hyperpolarizing factor, besides NO, in several types of arteries. Altogether, polyphenols have the capacity to improve the endothelial control of vascular tone not only in several experimental models of cardiovascular diseases such as hypertension but also in healthy and diseased humans. Thus, these experimental and clinical studies highlight the potential of polyphenol-rich sources to provide vascular protection in health and disease.

Papillary endothelial hyperplasia (Masson's tumor) in children.

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Liné, A; Sanchez, J; Jayyosi, L; Birembaut, P; Ohl, X; Poli-Mérol, M-L; François, C

2017-06-01

The intravascular papillary endothelial hyperplasia (IPEH/Masson's tumor) is a rare benign tumor of the skin and subcutaneous vessels. We report, in four pediatric cases, clinical presentation, care (diagnostic and surgical) of Masson's tumor in children. Two boys (two years) and two girls (four and six years) showed a pain subcutaneous tumor (one to five centimeters). They were in the transverse abdominal muscle, between two metatarsals, at the front of thigh and in the axilla. Imaging performed (MRI, Doppler ultrasound) evoked either a hematoma, a lymphangioma or hemangioma. The indication for removal was selected from pain and/or parental concern. The diagnosis was histologically. A lesion persisted in residual form (incomplete initial resection), and is currently not scalable for eleven years. This tumor is characterized by excessive proliferation and papillary endothelial cells in the vessels, following a thrombotic event. It is found mainly in adults (no specific age), and preferentially localizes in the face and limbs. The clinical differential diagnosis of this tumor is angiosarcoma. The imagery has not allowed in our series to diagnose but still essential to eliminate differential diagnoses. Only surgical excision with histological examination can differentiate. Our study emphasizes the possibility of pediatric cases with two cases of unusual locations (abdominal and axilla). Clinical presentations we met, now lead us to direct our histologist looking for a Masson tumor in any child with a subcutaneous tumor and/or intramuscular pain, sudden onset, and vascular appearance (after excluding an arteriovenous malformation). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sustained apnea induces endothelial activation.

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Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

2017-09-01

Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

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Taylor, R F; Price, T H; Schwartz, S M; Dale, D C

1981-01-01

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function. Images PMID:7007441

Vascular endothelial growth factor and its relationship with the dental pulp.

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Grando Mattuella, Leticia; Westphalen Bento, Leticia; de Figueiredo, José Antonio Poli; Nör, Jacques Eduardo; de Araujo, Fernando Borba; Fossati, Anna Christina Medeiros

2007-05-01

The dental pulp is a loose connective tissue located within rigid dentinal walls. Therefore, when subjected to a stimulus, the pulpal tissue has little expansion capacity. The defense mechanisms of this tissue include the formation of tertiary dentin as well as the production of signaling molecules that help in the repair. The dentin matrix is rich in growth factors (GFs) that, when diluted and diffused into the pulp tissue, aid the healing process of the dentinopulpar complex. The angiogenic GFs participate in this event. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, promotes endothelial cell survival and angiogenesis. Among its receptors, VEGFR-2 seems to be the most intimately associated with mitogenic activities, cell migration, vascular permeability, and survival of endothelial cells. This literature review addresses the cell-signaling process that occurs in response to a pulp stimulus up to its transduction in the target cell, describing the VEGF, as well as its characteristics and receptors. The reported studies have correlated the expression of VEGF and its potential functions that may have an impact on several dental specialties, thus indicating that further clinical investigations should be conducted in order to translate the results obtained until this moment primarily in laboratory experiments.

Endothelial Cells and Astrocytes: A Concerto en Duo in Ischemic Pathophysiology

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Vincent Berezowski

2012-01-01

Full Text Available The neurovascular/gliovascular unit has recently gained increased attention in cerebral ischemic research, especially regarding the cellular and molecular changes that occur in astrocytes and endothelial cells. In this paper we summarize the recent knowledge of these changes in association with edema formation, interactions with the basal lamina, and blood-brain barrier dysfunctions. We also review the involvement of astrocytes and endothelial cells with recombinant tissue plasminogen activator, which is the only FDA-approved thrombolytic drug after stroke. However, it has a narrow therapeutic time window and serious clinical side effects. Lastly, we provide alternative therapeutic targets for future ischemia drug developments such as peroxisome proliferator- activated receptors and inhibitors of the c-Jun N-terminal kinase pathway. Targeting the neurovascular unit to protect the blood-brain barrier instead of a classical neuron-centric approach in the development of neuroprotective drugs may result in improved clinical outcomes after stroke.

Cornea stress test--evaluation of corneal endothelial function in vivo by contact lens induced stress

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Saini Jagjit

1997-01-01

Full Text Available Reliable and valid assessment of corneal endothelial function is a critical input for diagnosing, prognosticating and monitoring progression of disorders affecting corneal endothelium. In 123 eyes, corneal endothelial function was assessed employing data from the corneal hydration recovery dynamics. Serial pachometric readings were recorded on Haag-Striet pachometer with Mishima-Hedbys modification before and after two hours of thick soft contact lens wear. Percentage Recovery Per Hour (PRPH was derived from raw data as an index of endothelial function. Assessed PRPH in pseudophakic corneal oedema and Fuchs′ endothelial dystrophy eyes (35.9 +/- 9.8% was significantly lower than normal controls (61.9 +/- 10.5%. On employing receiver operation characteristics curve analysis the tested results demonstrated high sensitivity (87% and specificity (92% for detection of low endothelial function at PRPH cut off of 47.5%. Using this PRPH cut off, 80% of Fuchs′ endothelial dystrophy and 93.3% of pseudophakic corneal oedema eyes could be demonstrated to have low endothelial function. A total of 66.7% of diabetic eyes also demonstrated PRPH of lower than 47.5%. Clear corneal grafts demonstrated PRPH values of 24.6% to 73.0%. Of 6 corneal grafts that demonstrated initial PRPH of lower than 47.5%, 4 failed within 4 to 6 months. Our data demonstrated high sensitivity and specificity of this corneal stress test. PRPH index was useful in quantifying endothelial function in clinical disorders including diabetes mellitus. The index PRPH was demonstrated to be useful in monitoring and prognosticating outcome of corneal grafts.

Physiologically assessed hot flashes and endothelial function among midlife women.

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Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

2017-08-01

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Periodontal treatment effects on endothelial function and cardiovascular disease biomarkers in subjects with chronic periodontitis: protocol for a randomized clinical trial

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2011-01-01

Background Periodontal disease (PD) is an infectious clinical entity characterized by the destruction of supporting tissues of the teeth as the result of a chronic inflammatory response in a susceptible host. It has been proposed that PD as subclinical infection may contribute to the etiology and to the pathogenesis of several systemic diseases including Atherosclerosis. A number of epidemiological studies link periodontal disease/edentulism as independent risk factor for acute myocardial infarction, peripheral vascular disease, and cerebrovascular disease. Moreover, new randomized controlled clinical trials have shown an improvement on cardiovascular surrogate markers (endothelial function, sICAM, hsPCR level, fibrinogen) after periodontal treatment. Nonetheless, such trials are still limited in terms of external validity, periodontal treatment strategies, CONSORT-based design and results consistency/extrapolation. The current study is designed to evaluate if periodontal treatment with scaling and root planning plus local delivered chlorhexidine improves endothelial function and other biomarkers of cardiovascular disease in subjects with moderate to severe periodontitis. Methods/Design This randomized, single-blind clinical trial will be performed at two health centers and will include two periodontal treatment strategies. After medical/periodontal screening, a baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD) and other systemic surrogate markers will be obtained from all recruited subjects. Patients then will be randomized to receive either supragingival/subgingival plaque cleaning and calculus removal plus chlorhexidine (treatment group) or supragingival plaque removal only (control group). A second and third FMD will be obtained after 24 hours and 12 weeks in both treatment arms. Each group will consist of 49 patients (n = 98) and all patients will be followed-up for secondary outcomes and will be monitored through a coordinating

Periodontal treatment effects on endothelial function and cardiovascular disease biomarkers in subjects with chronic periodontitis: protocol for a randomized clinical trial

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Arce Roger M

2011-02-01

Full Text Available Abstract Background Periodontal disease (PD is an infectious clinical entity characterized by the destruction of supporting tissues of the teeth as the result of a chronic inflammatory response in a susceptible host. It has been proposed that PD as subclinical infection may contribute to the etiology and to the pathogenesis of several systemic diseases including Atherosclerosis. A number of epidemiological studies link periodontal disease/edentulism as independent risk factor for acute myocardial infarction, peripheral vascular disease, and cerebrovascular disease. Moreover, new randomized controlled clinical trials have shown an improvement on cardiovascular surrogate markers (endothelial function, sICAM, hsPCR level, fibrinogen after periodontal treatment. Nonetheless, such trials are still limited in terms of external validity, periodontal treatment strategies, CONSORT-based design and results consistency/extrapolation. The current study is designed to evaluate if periodontal treatment with scaling and root planning plus local delivered chlorhexidine improves endothelial function and other biomarkers of cardiovascular disease in subjects with moderate to severe periodontitis. Methods/Design This randomized, single-blind clinical trial will be performed at two health centers and will include two periodontal treatment strategies. After medical/periodontal screening, a baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD and other systemic surrogate markers will be obtained from all recruited subjects. Patients then will be randomized to receive either supragingival/subgingival plaque cleaning and calculus removal plus chlorhexidine (treatment group or supragingival plaque removal only (control group. A second and third FMD will be obtained after 24 hours and 12 weeks in both treatment arms. Each group will consist of 49 patients (n = 98 and all patients will be followed-up for secondary outcomes and will be monitored

Expansion and maintenance of human embryonic stem cell–derived endothelial cells by TGFβ inhibition is Id1 dependent

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James, Daylon; Nam, Hyung-song; Seandel, Marco; Nolan, Daniel; Janovitz, Tyler; Tomishima, Mark; Studer, Lorenz; Lee, Gabsang; Lyden, David; Benezra, Robert; Zaninovic, Nikica; Rosenwaks, Zev; Rabbany, Sina Y; Rafii, Shahin

2010-01-01

Previous efforts to differentiate human embryonic stem cells (hESCs) into endothelial cells have not achieved sustained expansion and stability of vascular cells. To define vasculogenic developmental pathways and enhance differentiation, we used an endothelial cell–specific VE-cadherin promoter driving green fluorescent protein (GFP) (hVPr-GFP) to screen for factors that promote vascular commitment. In phase 1 of our method, inhibition of transforming growth factor (TGF)β at day 7 of differentiation increases hVPr-GFP+ cells by tenfold. In phase 2, TGFβ inhibition maintains the proliferation and vascular identity of purified endothelial cells, resulting in a net 36-fold expansion of endothelial cells in homogenous monolayers, which exhibited a transcriptional profile of Id1highVEGFR2highVE-cadherin+ ephrinB2+. Using an Id1-YFP hESC reporter line, we showed that TGFβ inhibition sustains Id1 expression in hESC-derived endothelial cells and that Id1 is required for increased proliferation and preservation of endothelial cell commitment. Our approach provides a serum-free method for differentiation and long-term maintenance of hESC-derived endothelial cells at a scale relevant to clinical application. PMID:20081865

Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome.

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Sonnenschein, Kristina; Horváth, Tibor; Mueller, Maja; Markowski, Andrea; Siegmund, Tina; Jacob, Christian; Drexler, Helmut; Landmesser, Ulf

2011-06-01

Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with metabolic syndrome.

Analysis of circulating hem-endothelial marker RNA levels in preterm infants

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Kuint Jacob

2009-06-01

Full Text Available Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30. Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2 and Scl/Tal1 in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA. We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.

Serial corneal endothelial cell loss with lathe-cut and injection-molded posterior chamber intraocular lenses.

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Kraff, M C; Sanders, D R; Lieberman, H L

1983-01-01

We compared endothelial cell loss of patients implanted with lathe-cut posterior chamber lenses and those implanted with injection-molded lenses over a three-year postoperative period. Results were based on more than 2,500 measurements of corneal endothelial density. Although the technique of cataract extraction (anterior chamber phacoemulsification, posterior chamber phacoemulsification, or planned extracapsular extraction) significantly affected cell loss (P less than .01), the type of implant (lathe-cut or injection-molded) did not. Significant continuing endothelial cell loss did not occur during the first three postoperative years with injection-molded lenses. There was, however, a statistically significant 7% to 15% additional cell loss after surgery over the first two to three postoperative years with lathe-cut implants. There have been no cases of corneal endothelial decompensation developing after implantation of injection-molded or lathe-cut lenses. Because a standard field clinical specular microscope was used in this study, cell counting errors cannot be ruled out as a cause of these findings.

Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

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Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

2013-11-01

Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

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Naosuke Kamei

2017-01-01

Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

Corneal endothelial morphology and function after torsional and longitudinal ultrasound mode phacoemulsification.

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Módis, László Jr; Szalai, Eszter; Flaskó, Zsuzsa; Németh, Gábor

2016-01-01

To study the endothelial cell morphology and corneal thickness changes after phacoemulsification by using the OZil torsional and longitudinal ultrasound techniques (Infiniti Vision System, Alcon Laboratories). Department of Ophthalmology, Clinical Center, University of Debrecen, Debrecen, Hungary. 52 patients with cataract were randomly assigned to longitudinal ultrasound and torsional mode group. All surgeries were performed through a 2.2 mm clear corneal incision, the method employed being divide and conquer. The endothelial morphometry such as cell density (ECD), mean cell area, coefficient of variation of cell area, and central corneal thickness were examined with specular microscopy (EM-1000, Tomey) preoperatively and 4, 8 weeks postoperatively. ECD values decreased significantly in both surgical groups (P .05). No significant correlation was found between the endothelial cell loss and the nucleus density. Both phacoemulsification techniques were safe and effective. The torsional handpiece performs oscillatory movements and delivers less energy into the eye than the longitudinal ultrasound technique, therefore providing more favorable energy and thermal safety profile.

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

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Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

2017-11-01

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

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Polverino, Francesca; Celli, Bartolome R.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested

In vivo endothelization of tubular vascular grafts through in situ recruitment of endothelial and endothelial progenitor cells by RGD-fused mussel adhesive proteins

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Kang, Tae-Yun; Lee, Jung Ho; Kang, Jo-A; Rhie, Jong-Won; Kim, Bum Jin; Cha, Hyung Joon; Hong, Jung Min; Kim, Byoung Soo; Cho, Dong-Woo

2015-01-01

The use of tissue mimics in vivo, including patterned vascular networks, is expected to facilitate the regeneration of functional tissues and organs with large volumes. Maintaining patency of channels in contact with blood is an important issue in the development of a functional vascular network. Endothelium is the only known completely non-thrombogenic material; however, results from treatments to induce endothelialization are inconclusive. The present study was designed to evaluate the clinical applicability of in situ recruitment of endothelial cells/endothelial progenitor cells (EC/EPC) and pre-endothelization using a recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) coating in a model of vascular graft implantation. Microporous polycaprolactone (PCL) scaffolds were fabricated with salt leaching methods and their surfaces were modified with collagen and MAP-RGD. We then evaluated their anti-thrombogenicity with an in vitro hemocompatibility assessment and a 4-week implantation in the rabbit carotid artery. We observed that MAP-RGD coating reduced the possibility of early in vivo graft failure and enhanced re-endothelization by in situ recruitment of EC/EPC (patency rate: 2/3), while endothelization prior to implantation aggravated the formation of thrombosis and/or IH (patency rate: 0/3). The results demonstrated that in situ recruitment of EC/EPC by MAP-RGD could be a promising strategy for vascular applications. In addition, it rules out several issues associated with pre-endothelization, such as cell source, purity, functional modulation and contamination. Further evaluation of long term performance and angiogenesis from the luminal surface may lead to the clinical use of MAP-RGD for tubular vascular grafts and regeneration of large-volume tissues with functional vascular networks. (paper)

Aberrant overexpression of vascular endothelial growth factor in pancreatic ductal adenocarcinoma is associated with aggressive clinical behavior

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Naomi Y Jiang

2010-07-01

Full Text Available Naomi Y Jiang1, Bruce A Woda2, Liping Zhang2, Suyang Hao2, Karen A Dresser2, Di Lu21Massachusetts Institute of Technology, Worcester, MA, USA; 2Department of Pathology, University of Massachusetts Medical Center, Worcester, MA, USAAbstract: Pancreatic adenocarcinoma is a leading cause of cancer-related deaths in the United States. In this study, we studied vascular endothelial growth factor (VEGF expression in ­pancreatic adenocarcinoma by immunohistochemical staining. Clinical follow-up and survival data were analyzed. We determined that VEGF was aberrantly overexpressed in a subset of primary pancreatic adenocarcinoma. Statistically, VEGF overexpression was associated with higher stage, higher grade, and lymph node metastasis (P < 0.001, P = 0.012, and P < 0.005, respectively. Additionally, patients of this subset had a much shorter overall survival than patients without VEGF overexpression, as evidenced by Kaplan–Meier plots and the log-rank test (P = 0.001. The 5-year overall survival rate was 17% in patients with VEGF overexpression compared to 52% in patients without VEGF overexpression. The median survival was only 13 months for patients with VEGF overexpression compared to 65 months for patients without. In conclusion, VEGF is a biomarker that identifies a subset of pancreatic ductal adenocarcinoma with aggressive clinical behavior.Keywords: pancreatic adenocarcinoma, VEGF, cancer

Proteomic analysis of endothelial cold-adaptation

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Zieger Michael AJ

2011-12-01

Full Text Available Abstract Background Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. Results Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine

Endothelial and circulating progenitor cells in hematological diseases and allogeneic hematopoietic stem cell transplantation.

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Ruggeri, Annalisa; Paviglianiti, Annalisa; Volt, Fernanda; Kenzey, Chantal; Rafii, Hanadi; Rocha, Vanderson; Gluckman, Eliane

2017-10-12

Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells which are not associated with vessel walls, and that are detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and some other diseases. Consequently, CECs and EPCs represent a potential biomarker in several clinical conditions involving endothelial turnover and remodeling, such as hematological diseases. These cells may be involved in disease progression and the neoplastic angiogenesis process. Moreover, CESs and EPCs are probably involved in endothelial damage that is a marker of several complications following allogeneic hematopoietic stem cell transplantation. This review aims to provide an overview on the characterization of CECs and EPCs, describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

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N. N. Kushnarenko

2015-09-01

Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

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E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

Pars Plana-Modified versus Conventional Ahmed Glaucoma Valve in Patients Undergoing Penetrating Keratoplasty: A Prospective Comparative Randomized Study.

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Parihar, Jitendra Kumar Singh; Jain, Vaibhav Kumar; Kaushik, Jaya; Mishra, Avinash

2017-03-01

To compare the outcome of pars-plana-modified Ahmed glaucoma valve (AGV) versus limbal-based conventional AGV into the anterior chamber, in patients undergoing penetrating keratoplasty (PK) for glaucoma with coexisting corneal diseases. In this prospective randomized clinical trial, 58 eyes of 58 patients with glaucoma and coexisting corneal disease were divided into two groups. Group 1 (29 eyes of 29 patients) included patients undergoing limbal-based conventional AGV into the anterior chamber (AC) along-with PK and group 2 (29 eyes of 29 patients) included those undergoing pars-plana-modified AGV along-with PK. Outcome measures included corneal graft clarity, intraocular pressure (IOP), number of antiglaucoma medications, and postoperative complications. Patients were followed up for a minimum period of 2 years. Out of 58 eyes (58 patients), 50 eyes (50 patients: 25 eyes of 25 patients each in group 1 and group 2) completed the study and were analyzed. Complete success rate for AGV (group 1: 76%; group 2: 72%; p = 0.842) and corneal graft clarity (group 1: 68%; group 2: 76%; p = 0.081) were comparable between the two groups at 2 years. Graft failure was more in conventional AGV (32%) as compared to pars plana-modified AGV (24%) but not statistically significant (p = 0.078) at 2 years. Though both procedures were comparable in various outcome measures, pars-plana-modified AGV is a viable option for patients undergoing PK, as it provides a relatively better corneal graft survival rate and lesser complications that were associated with conventional AGV.

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein.

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Li, Zhijuan; Cheng, Jianxin; Wang, Liping

2015-10-30

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. Copyright © 2015. Published by Elsevier Inc.

Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

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Milardi, Domenico; Grande, Giuseppe; Giampietro, Antonella; Vendittelli, Francesca; Palumbo, Sara; Tartaglione, Linda; Marana, Riccardo; Pontecorvi, Alfredo; de Marinis, Laura; Zuppi, Cecilia; Capoluongo, Ettore

2012-01-01

Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

Cardiac endothelial cells isolated from mouse heart - a novel model for radiobiology

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Jelonek, K.; Walaszczyk, A.; Gabrys, D.; Pietrowska, M.; Widlak, P.; Kanthou, Ch.

2011-01-01

Cardiovascular disease is recognized as an important clinical problem in radiotherapy and radiation protection. However, only few radiobiological models relevant for assessment of cardiotoxic effects of ionizing radiation are available. Here we describe the isolation of mouse primary cardiac endothelial cells, a possible target for cardiotoxic effects of radiation. Cells isolated from hearts of juvenile mice were cultured and irradiated in vitro. In addition, cells isolated from hearts of locally irradiated adult animals (up to 6 days after irradiation) were tested. A dose-dependent formation of histone γH 2 A.X foci was observed after in vitro irradiation of cultured cells. However, such cells were resistant to radiation-induced apoptosis. Increased levels of actin stress fibres were observed in the cytoplasm of cardiac endothelial cells irradiated in vitro or isolated from irradiated animals. A high dose of 16 Gy did not increase permeability to Dextran in monolayers formed by endothelial cells. Up-regulated expression of Vcam1, Sele and Hsp70i genes was detected after irradiation in vitro and in cells isolated few days after irradiation in vivo. The increased level of actin stress fibres and enhanced expression of stress-response genes in irradiated endothelial cells are potentially involved in cardiotoxic effects of ionizing radiation. (authors)

Intrastromal Corneal Ring Segments for Astigmatism Correction after Deep Anterior Lamellar Keratoplasty

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Júlio C. D. Arantes

2017-01-01

Full Text Available Background. To evaluate the change in corneal astigmatism after intrastromal corneal ring segment (ICRS implantation in keratoconus patients with previous deep anterior lamellar keratoplasty (DALK. Design was a longitudinal, retrospective, interventional study. The study included 25 eyes of 24 patients with keratoconus who had DALK performed at least two years prior to ICRS implantation. All patients had a clear corneal graft with up to 8.00 D of corneal astigmatism and intolerance to contact lenses. The studied parameters were age, sex, corrected distance visual acuity (CDVA, maximum keratometry (K1, minimum keratometry (K2, spherical equivalent, and astigmatism. There was a statistically significant decrease in the postintervention analysis as follows: 3.5 D reduction in K1 (p<0.001; 1.53 D in K2 (p=0.005; and 2.52 D (p<0.001 in the average K. The spherical equivalent reduced from −3.67 D (±2.74 to −0.71 D (±2.35 (p<0.001. The topographic astigmatism reduced from 3.87 D preoperatively to 1.90 D postoperatively (p<0.001. The CDVA improved from 0.33 (±0.10 to 0.20 (±0.09, p<0.001. ICRS implantation is a useful option for the correction of astigmatism after DALK as it yields significant visual, topographic, and refractive results.

Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

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Jason Tran

Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

Correction of High Astigmatism after Penetrating Keratoplasty with Toric Multifocal Intraocular Lens Implantation

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Raffaele Nuzzi

2017-07-01

Full Text Available After penetrating keratoplasty (PK, high astigmatism is often induced, being frequently about 4–6 dpt. According to the entity and typology of astigmatism, different methods of correction can be used. Selective suture removal, relaxing incisions, wedge resections, compression sutures, photorefractive keratectomy, and laser-assisted in situ keratomileusis can reduce corneal astigmatism and ametropia, but meanwhile they can cause a reduction in the corneal integrity and cause an over- or undercorrection. In case of moderate-to-high regular astigmatisms, the authors propose a toric multifocal intraocular lens (IOL implantation to preserve the corneal integrity (especially in PK after herpetic corneal leukoma keratitis. We evaluated a 45-year-old patient who at the age of 30 was subjected to PK in his left eye due to corneal leukoma herpetic keratitis, which led to high astigmatism (7.50 dpt cyl. 5°. The patient was subjected to phacoemulsification and customized toric multifocal IOL implantation in his left eye. The correction of PK-induced residual astigmatism with a toric IOL implantation is an excellent choice but has to be evaluated in relation to patient age, corneal integrity, longevity graft, and surgical risk. It seems to be a well-tolerated therapeutic choice and with good results.

Effects of the PPARγ agonist troglitazone on endothelial cells in vivo and in vitro: Differences between human and mouse

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Kakiuchi-Kiyota, Satoko; Vetro, Joseph A.; Suzuki, Shugo; Varney, Michelle L.; Han, Huai-Yun; Nascimento, Merielen; Pennington, Karen L.; Arnold, Lora L.; Singh, Rakesh K.; Cohen, Samuel M.

2009-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists have been or are being developed for clinical use in the treatment of type 2 diabetes mellitus and hyperlipidemias. A common tumor finding in rodent carcinogenicity studies for these agonists is hemangioma/hemangiosarcoma in mice but not in rats. We hypothesized that increased endothelial cell proliferation may be involved in the mechanism of PPAR agonist-induced vascular tumors in mice, and we investigated the effects on endothelial cells utilizing troglitazone, the first clinically used PPARγ agonist, in vivo and in vitro. Troglitazone (400 and 800 mg/kg/day) induced hemangiosarcomas in mice in a 2-year bioassay. We showed that troglitazone increased endothelial cell proliferation in brown and white adipose tissue and liver in mice at sarcomagenic doses after 4 weeks of treatment. Troglitazone was cytotoxic both to human dermal microvascular endothelial cells (HMEC1) and mouse mammary fat pad microvascular endothelial cells (MFP MVEC) at high concentrations. However, MFP MVEC were more resistant to the cytotoxic effects of troglitazone based on the much lower LC 50 in HMEC1 (17.4 μM) compared to MFP MVEC (92.2 μM). Troglitazone increased the proliferation and survival of MFP MVEC but not HMEC1 in growth factor reduced conditions. Our data demonstrate that troglitazone may induce hemangiosarcomas in mice, at least in part, through enhancement of survival and proliferation of microvascular endothelial cells. Such an effect does not occur with human cells, suggesting that human may react differently to exposure to PPAR agonists compared with mice.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

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Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

The research on endothelial function in women and men at risk for cardiovascular disease (REWARD study: methodology

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Lavoie Kim L

2011-08-01

Full Text Available Abstract Background Endothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR test (a proxy measure of endothelial function for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1 endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2 endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men. Methods/Design A total of 1972 patients (812 men and 1160 women undergoing a dipyridamole stress testing were recruited. Medical history, CVD risk factors, health behaviours, psychological status, and gender identity were assessed via structured interview or self-report questionnaires at baseline. In addition, FHR was assessed, as well as levels of sex hormones via blood draw. Patients will be followed for 5 years to assess major CVD events (cardiac mortality, non-fatal MI, revascularization procedures, and cerebrovascular events. Discussion This is the first study to determine the extent and nature of any sex differences in the ability of endothelial function to predict CVD events. We believe the results of this study will provide data that will better inform the choice of diagnostic tests in men and women and bring the quality of

ITE inhibits growth of human pulmonary artery endothelial cells.

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Pang, Ling-Pin; Li, Yan; Zou, Qing-Yun; Zhou, Chi; Lei, Wei; Zheng, Jing; Huang, Shi-An

2017-10-01

Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.

Safety of intracameral injection of gatifloxacin, levofloxacin on corneal endothelial structure and viability.

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Choi, Jin A; Chung, Sung Kun

2009-10-01

To investigate the safety of intracameral injection of gatifloxacin, levofloxacin in a rabbit model as prophylaxis against endophthalmitis. Twenty-four eyes of New Zealand white rabbits were randomly divided into 3 treatment groups: levofloxacin, gatifloxacin, and balanced salt solution (BSS) control groups. After 100 microL of each was injected into the anterior chamber, endothelial toxicity was evaluated by measuring the central corneal thicknesses and the clinical toxicity scores using a slit-lamp at post-procedure days 3 and 7. The percent of dead cells was determined by vital staining with alizarin red and trypan blue at 7 days after injection. Finally, in each group, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed for the evaluation of structural integrity. The toxicity scores were increased at post-procedure days 3 and 7, but the difference among the groups was not statistically significant (P = 0.661, 0.216, respectively). With regard to baseline corneal thickness, only the levofloxacin group exhibited a significant increase from baseline (P = 0.028), whereas the other treatment groups showed no difference from baseline (P = 0.128 in gatifloxacin, 0.161 in BSS group). The mean corneal endothelial damage was 0.81 +/- 0.31% in the levofloxacin group, 0.56 +/- 0.47% in the gatifloxacin group, and 0.53 +/- 0.52% in the BSS group, with no statistically significant difference noted among the groups (P = 0.582). SEM revealed a well-preserved hexagonal endothelial cell mosaic and normal microvilli on the endothelial cell surface in the gatifloxacin and control groups. However, the levofloxacin group showed slightly disintegrated cellular borders. TEM revealed that each group maintained normal intracellular organization, whereas the levofloxacin group exhibited slightly flat cell configuration with irregular folds on the apical cell surface. Intracameral injection of gatifloxacin and levofloxacin was nontoxic in terms of

Effect of Keishibukuryogan on Endothelial Function in Patients with at Least One Component of the Diagnostic Criteria for Metabolic Syndrome: A Controlled Clinical Trial with Crossover Design

Directory of Open Access Journals (Sweden)

Yutaka Nagata

2012-01-01

Full Text Available We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan, a traditional Japanese (Kampo formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000 in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval or group B (first control, then KBG-treatment. In forty-nine (27, group A; 22, group B patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI increased and those of serum nonesterified fatty acid (NEFA, malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

Management of Extreme Ametropia after Penetrating Keratoplasty: A Series of Surgical Procedures for High Myopia and Astigmatism

Directory of Open Access Journals (Sweden)

Jorge E. Valdez-Garcia

2014-08-01

Full Text Available A series of surgical interventions - relaxing corneal incisions, intraocular lens, and intrastromal rings - were used to correct a case of extreme ametropia in a thin cornea after a penetrating keratoplasty in an 18-year-old patient who presented with a -10.25 -8.50 × 120 preoperative refraction and 20/200 best-corrected visual acuity (BCVA. After a series of surgical procedures, the patient's BCVA in his left eye improved to 20/30 with +0.50 -1.00 × 170, the slit lamp examination showed no significant findings, and the patient's visual complaints disappeared. At the 1-year follow-up, the BCVA was 20/25, without visual complaints. The process of individualizing the surgical procedure in the present case was employed in an outcome-based approach, that is, the next surgical procedure was defined after the surgery and postoperative evaluation. The patient did not present complications during the follow-up period of 2.5 years.

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

Science.gov (United States)

Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

Science.gov (United States)

Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

2016-01-01

Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effect of femtosecond laser-assisted cataract surgery (flacs) on endothelial cell count

International Nuclear Information System (INIS)

Khan, M.S.; Habib, A.; Ishaq, M.; Yaqub, A.

2017-01-01

Objective:To compare the change in endothelial cell count after femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification. Study Design:Randomized controlled clinical trial. Place and Duration of Study:Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from January 2016 to August 2017. Methodology:Patients with senile cataract and age ranging from 40 to 80 years were included in the study. Patients with any other cause of endothelial cell loss, history of trauma, documented diabetes millitis, hypertention and glaucoma were excluded. Preoperative detailed ocular examination, including both anterior and posterior examination, was carried out. Patients were distributed into two groups. Group GP were planned for conventional phacoemulsification, while group GF underwent FLACS. All the surgeries were performed under local anesthesia by same ophthalmic surgeon. Specular microscope (Topcon specular microscope sp-3000p) was utilized to measure the endothelial cell count (ECC) before and 4 weeks after the surgery. Results:Fifty eyes (25 in each group) of 48 patients underwent cataract surgery by phacoemulsification or FLACS. Twenty-five (52.08%) out of the total were females while 23 (47.91%) were males. Median age of the participants in hacoemulsification group was 55 years (IQR 20.50), while in FLACS group it was 54 years (IQR 8). The median change in endothelial cell count was 228 (IQR 532) in Phaco group, while 23 (IQR 35) in FLACS group. (p<0.05 Mann Whitney U-test). Conclusion:FLACS is a safe and effective modality for cataract treatment and it induces significantly less endothelial cell loss than conventional phacoemulsification. (author)

[Undifferentiated cutaneous angiosarcoma of the head: identification by the endothelial marker Ulex europaeus agglutinin I].

Science.gov (United States)

Bork, K; Fries, J; Hoede, N; Korting, G W; Dienes, P

1985-06-01

Cutaneous angiosarcoma of the head is a rare tumor of the elderly and can occur in an undifferentiated form without any clinical or histological signs of the vascular origin of this tumor. In these cases, the tumor can be identified by using endothelial cell markers, such as factor-VIII-related antigen and ulex europaeus agglutinin I, in an immunofluorescence technique or a peroxidase-antiperoxidase method. A 78-year-old patient is described who died within 18 months from such a tumor, which was diagnosed using the endothelial cell marker, ulex europaeus agglutinin I.

Reduced Ang2 expression in aging endothelial cells.

Science.gov (United States)

Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

2016-06-03

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.

Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

DEFF Research Database (Denmark)

Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

2018-01-01

PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

Oxidative stress induced pulmonary endothelial cell proliferation is ...

African Journals Online (AJOL)

Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

DEFF Research Database (Denmark)

Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

2014-01-01

We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission...... electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

Delivering minocycline into brain endothelial cells with liposome-based technology

OpenAIRE

Xing, Changhong; Levchenko, Tatyana; Guo, Shuzhen; Stins, Monique; Torchilin, Vladimir P; Lo, Eng H

2012-01-01

Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis facto...

The endothelial border to health

DEFF Research Database (Denmark)

Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

2017-01-01

player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma...... extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses...... to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should...

Radioprotection of mouse CNS endothelial cells in vivo

International Nuclear Information System (INIS)

Lyubimova, N.; Coultas, P.; Martin, R.

1996-01-01

Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

Directory of Open Access Journals (Sweden)

Elvira Pelosi

Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

A practical femtosecond laser procedure for DLEK endothelial transplantation: cadaver eye histology and topography.

Science.gov (United States)

Terry, Mark A; Ousley, Paula J; Will, Brian

2005-05-01

The manual dissection technique for deep lamellar endothelial keratoplasty (DLEK) surgery is technically difficult and may not be smooth enough for consistently optimal postoperative vision. We evaluated the feasibility and efficacy of using a femtosecond laser to perform the dissections in the DLEK procedure. The Intralase femtosecond laser (with standard LASIK surgery spot settings) was used to create a 9.4-mm wide, 400-microm deep lamellar pocket dissection and a 5.0-mm wide side cut near-exit incision in 10 "recipient" whole cadaver eyes and in 10 "donor" cadaver corneal-scleral caps mounted onto an artificial anterior chamber. Recipient and donor disks were resected with special scissors, and the donor tissue was transplanted using the small incision (5.0-mm) DLEK technique. Topography of the recipient eyes was measured pre- and postlaser dissection, and the recipient and donor tissues were sent for scanning electron microscopy (SEM) analysis of the smoothness of the dissections. Successful lamellar dissections were obtained in all tissues. The mean recipient topographic corneal curvature postoperatively was 43.3 +/- 1.7 diopters, which was not a significant change from the preoperative curvature of 44.0 +/- 0.8 diopters (P = 0.430). The mean recipient topographic astigmatism postoperatively was 1.7 +/- 0.8 diopters, which was not a significant change from the preoperative recipient astigmatism of 1.6 +/- 0.7 diopters (P = 0.426). Comparison of the histology of the laser-formed stromal dissections by scanning electron microscopy, however, did not appear significantly better than histology after manual DLEK dissections in either the recipient or the donor tissues. A femtosecond laser can create the lamellar dissections for the DLEK procedure, making this procedure easier and faster. As in the manual technique, corneal topography is unchanged by this surgery. More work will need to be done, however, to optimize the laser settings to provide even smoother

Endothelial remodelling and intracellular calcium machinery.

Science.gov (United States)

Moccia, F; Tanzi, F; Munaron, L

2014-05-01

Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

CLINICAL FEATURES, DIAGNOSIS, THE RESULTS OF THERAPEUTIC AND SURGICAL TREATMENT OF ACANTHAMOEBIC KERATITIS

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Evg. A. Kasparova

2017-01-01

Full Text Available Purpose: to describe our experience in Acanthamoeba keratitis diagnostics and treatment in the FGBNU Research Institute of eye diseases, Moscow.Patients and Methods. We observed 24 patients (25 eyes with the Acanthamoeba keratitis (AK. The age ranged from 18 to 47 years. All patients, except one, were contact lenses wearers. Clinical signs included superficial epithelial-stromal lesions in 8 patients (8 eyes, stromal forms of AK- in 16 patients (17 eyes, and mixed keratitis in 9 (9 eyes. We used confocal microscopy, conjunctival smearing and blood immunofluorescent analysis for HSV types I and II. 8 patients (8 eyes underwent penetrating keratoplasty (PKP and their corneal buttons were morphologically examined. AK treatment included 2 biguanid antiseptics — a PHMB ("Comfort-drops" — solution for contact lenses care and 0.025% solution of a chlorhexidini bigluconati, or "Vitabact" in frequent instillations. We also used Diflucan solution 0.2% instillations — 6–8 times a day in, and Orungal or Diflucan per os (200 mg once a day. Eye drops of aminoglycozide or fluorhinolon groups were added to the treatment as well. In the cases of mixed Acanthamoeba and HSV keratitis we used anti-herpetic medications (Poludan, Acyclovir.Results. Cysts were found with confocal microscopy in 66% examined patients, and in 75% of the corneal buttons after keratoplasty. 15 cases (60% healed with various intensity opacities. We removed corneal epithelium in 2 patients with poor effect of the medication treatment. 8 patients (8 eyes underwent PKP with transparent (2 patients and a semi-transparent engraftment (2 patients, in 4 cases (4 eyes AK recurrences had occurred, what required repeated surgery. Long persistence of Acanthamoeba cysts in the cornea after clinical recovery caused the admission of 2 antiseptic biguanids eye drops for 6–20 months in all patients. There were no recurrences in the group of patients during the observation period (range 1 to 6

Dietary phosphorus acutely impairs endothelial function.

Science.gov (United States)

Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

2009-07-01

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

Science.gov (United States)

Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

Verocytotoxin-induced apoptosis of human microvascular endothelial cells.

Science.gov (United States)

Pijpers, A H; van Setten, P A; van den Heuvel, L P; Assmann, K J; Dijkman, H B; Pennings, A H; Monnens, L A; van Hinsbergh, V W

2001-04-01

The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-alpha interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-alpha-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

Resveratrol: A Multifunctional Compound Improving Endothelial Function

OpenAIRE

Li, Huige; F?rstermann, Ulrich

2009-01-01

The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

Endothelial dysfunction – A predictor of atherosclerosis | Chhabra ...

African Journals Online (AJOL)

Endothelial dysfunction is a systemic disorder and a critical element in the pathogenesis of atherosclerotic diseases and its complications. Growing evidences suggest that the individual burden of currently known cardiovascular risk factors is not the only determinant of endothelial function; rather endothelial integrity ...

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

Science.gov (United States)

Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

2016-01-12

The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial.

Science.gov (United States)

Bondonno, Nicola P; Bondonno, Catherine P; Blekkenhorst, Lauren C; Considine, Michael J; Maghzal, Ghassan; Stocker, Roland; Woodman, Richard J; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2018-02-01

The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F 2 -isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO 3 - ) and nitrite (NO 2 - ) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p flavonoid metabolites (p effect of apple skin on endothelial function, both acutely and chronically. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Corneal endothelial cell density after femtosecond thin-flap LASIK and PRK for myopia: a contralateral eye study.

Science.gov (United States)

Smith, Ryan T; Waring, George O; Durrie, Daniel S; Stahl, Jason E; Thomas, Priscilla

2009-12-01

To compare the effect of femtosecond thinflap LASIK and photorefractive keratectomy (PRK) on postoperative endothelial cell density. In a prospective, randomized, contralateral, single-center clinical trial, 25 patients (mean age: 30+/-5 years [range: 21 to 38 years]) underwent PRK in one eye and thin-flap LASIK in the fellow eye for the correction of myopia using a wavefront-guided platform. The central corneal endothelial cell density was measured using the NIDEK Confoscan 4 preoperatively, and at 1 and 3 months postoperatively. Changes in endothelial cell density were analyzed over time between the two refractive techniques. In PRK, the average preoperative endothelial cell density was 3011+/-329 cells/mm(2), which decreased to 2951+/-327 cells/mm(2) at 1 month (P=.5736) and 2982+/-365 cells/mm(2) at 3 months (P=.6513). In thinflap LASIK, the average preoperative endothelial cell density was 2995+/-325 cells/mm(2), which decreased to 2977+/-358 cells/mm(2) at 1 month (P=.5756) and 2931+/-369 cells/mm(2) at 3 months (P=.4106). No statistically significant difference was found between the two groups at 1 (P=.7404) or 3 (P=.3208) months postoperatively. No statistically significant change was noted in endothelial cell density following either PRK or thin-flap LASIK for the treatment of myopia. Furthermore, no statistically significant difference was found between the two groups out to 3 months postoperatively, indicating that thin-flap LASIK is as safe as PRK with regards to endothelial health.

Magnetizable stent-grafts enable endothelial cell capture

Energy Technology Data Exchange (ETDEWEB)

Tefft, Brandon J. [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Uthamaraj, Susheil [Division of Engineering, Mayo Clinic, Rochester, MN (United States); Harburn, J. Jonathan [School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees (United Kingdom); Hlinomaz, Ota [Department of Cardioangiology, St. Anne' s University Hospital, Brno (Czech Republic); Lerman, Amir [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Dragomir-Daescu, Dan [Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN (United States); Sandhu, Gurpreet S., E-mail: sandhu.gurpreet@mayo.edu [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States)

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance. - Highlights: • Magnetic stent-grafts were made from 2205 steel stents and polyurethane nanofibers. • Stent-grafts remained patent and formed a thin and uniform neointima when implanted. • Stent-grafts captured endothelial cells labeled with magnetic nanoparticles. �

Association between sympathoadrenal activation, fibrinolysis, and endothelial damage in septic patients

DEFF Research Database (Denmark)

Johansson, Pär I; Haase, Nicolai; Perner, Anders

2014-01-01

for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation......-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all PPAI-1 (all P

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis.

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Loffredo, L; Baratta, F; Ludovica, P; Battaglia, S; Carnevale, R; Nocella, C; Novo, M; Pannitteri, G; Ceci, F; Angelico, F; Violi, F; Del Ben, M

2018-02-01

Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

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Shumei Man

2008-01-01

Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

Clinical evaluation of the endothelial tie-2 crossmatch in ABO compatible and ABO incompatible renal transplants.

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Kafetzi, Maria L; Boletis, John N; Melexopoulou, Christine A; Tsakris, Athanassios; Iniotaki, Aliki G; Doxiadis, Ilias I N

2013-11-01

The necessity of detection of other than the classical major histocompatibility complex (MHC) and MHC class I-related chain A (MICA) directed antibodies prior to organ transplantation has already been repeatedly reported. A commercial flow cytometric endothelial crossmatch (CM) using isolated peripheral blood tie-2 positive cells provides a tool to detect non-MHC antibodies in addition to antibodies directed to MHC class I and II. The vast majority of circulating tie-2 positive cells expresses HLA-DR but not the A, B blood group antigens. Tie-2 cells are circulating surrogate endothelial cells. In this retrospective study we evaluated the endothelial CM in 51 renal transplantations, 30 with ABO compatible grafts and 21 with ABO incompatible grafts. Fifteen of the ABO compatible recipients (group A) developed unexplained rejection episodes (RE) while the remaining 15 had no RE (group B). Five cases of group A and none of group B had a positive tie-2 CM before transplantation (p=0.042). A positive tie-2 CM was also correlated with graft failure in ABO compatible transplants (p=0.02). No significant correlation was found between a positive pre-transplant tie-2 CM and RE in the ABO incompatible group. This study strongly suggest that a positive tie-2 CM may predict post-transplantation complications in ABO compatible grafts while negative reactions are not predictive. The test is not significantly correlated with RE in ABO incompatible grafts possibly due to applied desensitization. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Acidic pH reduces VEGF-mediated endothelial cell responses by downregulation of VEGFR-2; relevance for anti-angiogenic therapies.

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Faes, Seraina; Uldry, Emilie; Planche, Anne; Santoro, Tania; Pythoud, Catherine; Demartines, Nicolas; Dormond, Olivier

2016-12-27

Anti-angiogenic treatments targeting the vascular endothelial growth factor or its receptors have shown clinical benefits. However, impact on long-term survival remains limited. Solid tumors display an acidic microenvironment that profoundly influences their biology. Consequences of acidity on endothelial cells and anti-angiogenic therapies remain poorly characterized and hence are the focus of this study. We found that exposing endothelial cells to acidic extracellular pH resulted in reduced cell proliferation and migration. Also, whereas VEGF increased endothelial cell proliferation and survival at pH 7.4, it had no effect at pH 6.4. Furthermore, in acidic conditions, stimulation of endothelial cells with VEGF did not result in activation of downstream signaling pathways such as AKT. At a molecular level, acidity significantly decreased the expression of VEGFR-2 by endothelial cells. Consequently, anti-angiogenic therapies that target VEGFR-2 such as sunitinib and sorafenib failed to block endothelial cell proliferation in acidic conditions. In vivo, neutralizing tumor acidity with sodium bicarbonate increased the percentage of endothelial cells expressing VEGFR-2 in tumor xenografts. Furthermore, combining sodium bicarbonate with sunitinib provided stronger anti-cancer activity than either treatment alone. Histological analysis showed that sunitinib had a stronger anti-angiogenic effect when combined with sodium bicarbonate. Overall, our results show that endothelial cells prosper independently of VEGF in acidic conditions partly as a consequence of decreased VEGFR-2 expression. They further suggest that strategies aiming to raise intratumoral pH can improve the efficacy of anti-VEGF treatments.

Endothelial cells in the eyes of an immunologist.

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Young, M Rita

2012-10-01

Endothelial cell activation in the process of tumor angiogenesis and in various aspects of vascular biology has been extensively studied. However, endothelial cells also function in other capacities, including in immune regulation. Compared to the more traditional immune regulatory populations (Th1, Th2, Treg, etc.), endothelial cells have received far less credit as being immune regulators. Their regulatory capacity is multifaceted. They are critical in both limiting and facilitating the trafficking of various immune cell populations, including T cells and dendritic cells, out of the vasculature and into tissue. They also can be induced to stimulate immune reactivity or to be immune inhibitory. In each of these parameters (trafficking, immune stimulation and immune inhibition), their role can be physiological, whereby they have an active role in maintaining health. Alternatively, their role can be pathological, whereby they contribute to disease. In theory, endothelial cells are in an ideal location to recruit cells that can mediate immune reactivity to tumor tissue. Furthermore, they can activate the immune cells as they transmigrate across the endothelium into the tumor. However, what is seen is the absence of these protective effects of endothelial cells and, instead, the endothelial cells succumb to the defense mechanisms of the tumor, resulting in their acquisition of a tumor-protective role. To understand the immune regulatory potential of endothelial cells in protecting the host versus the tumor, it is useful to better understand the other circumstances in which endothelial cells modulate immune reactivities. Which of the multitude of immune regulatory roles that endothelial cells can take on seems to rely on the type of stimulus that they are encountering. It also depends on the extent to which they can be manipulated by potential dangers to succumb and contribute toward attack on the host. This review will explore the physiological and pathological roles

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes

DEFF Research Database (Denmark)

Spijkerman, Annemieke M W; Gall, Mari-Anne; Tarnow, L

2007-01-01

AIMS: To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. METHODS: Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during.......65 (1.21-2.25). CONCLUSIONS: In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes......E-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. RESULTS: The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary...

Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

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Jeanine M. Roodhart

2010-01-01

Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

Pre-banking microbial contamination of donor conjunctiva and storage medium for penetrating keratoplasty.

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Inomata, Takenori; Ono, Koichi; Matsuba, Tsuyoshi; Shiang, Tina; Di Zazzo, Antonio; Nakatani, Satoru; Yamaguchi, Masahiro; Ebihara, Nobuyuki; Murakami, Akira

2017-09-01

The aims of this study were to investigate the incidence of positive donor tissue cultures before transfer to preservation medium (Optisol™-GS) for penetrating keratoplasty, to verify the efficacy of antibiotics contained in Optisol™-GS by examining the drug susceptibility and to assess the relationship between the results of our microbial assessments as well as donor factors and the incidence of contamination. We conducted a retrospective, cross-sectional study using Juntendo Eye Bank records for all corneal transplantations. Two hundred donor conjunctiva harvestings and storage medium (EP-II ® ) cultures were performed between July 2008 and June 2011. We analyzed the associations between donor factors (age, gender, history of cataract surgery, death-to-preservation interval, cause of death) and contamination rates using multivariate analysis by the generalized estimating equation model. We obtained positive bacterial cultures from 154 of the 200 eyes (77.0%). The isolated bacteria were indigenous, such as coagulase-negative Staphylococci, Corynebacterium sp., and methicillin-resistant Staphylococcus aureus (MRSA). There was significant resistance to levofloxacin (18 eyes, 9.0%) and gentamicin (12 eyes, 6.0%), and no vancomycin-resistant bacteria were detected. The donor factors did not correlate with the prevalence of bacterial contamination in our criteria. Pre-banking microbial assessment allows for microbial detection, bacterial susceptibility and resistance testing. This is useful for developing preservation mediums containing effective spectrum antibiotic agents for high quality control of corneal banking.

Long-term outcomes of penetrating keratoplasty in keratoconus:analysis of the factors associated with final visual acuities

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Jin A Choi

2014-06-01

Full Text Available AIM: To investigate the long-term results of penetrating keratoplasty (PK in patients with keratoconus (KC and to evaluate factors that might influence the final visual outcome.METHODS:We retrospectively reviewed the data of all patients with clinical KC who had undergone PK by a single corneal surgeon in a single center from May 1980 to December 2005. The age of the patients, preoperative best-corrected visual acuity (BCVA, corneal thickness, death to preservation time, and preservation to transplantation time were recorded. Additionally, postoperative complications such as graft rejection, development of glaucoma and specular microscopy were checked during the follow-up.RESULTS:Sixty-nine eyes from 69 patients were finally included. The follow-up period was 8.64±6.13y. Graft rejection occurred in 4 eyes of 69 cases (5.8%, and the time to graft rejection was 2.1±1.3y. A Kaplan–Meier survival analysis showed that the estimated cumulative probability of graft rejection at 6, 13, and 17y after PK were 95.6%, 90.0%, and 78.8%, respectively. When we evaluated factors that might influence final BCVA in eyes, no disparity donor-host trephine size (same graft size as well as higher spherical equivalent, and average K-value were associated with higher final BCVA. (P=0.006, 0.051, 0.092, and 0.021 in eyes with follow-up <8y; P=0.068, 0.065, and 0.030 in eyes with follow-up ≥8y, respectively.CONCLUSION: The long-term results of PK in patients with KC were favorable with a high percentage of good BCVA. Less myopic change and low average K-reading, as well as a surgical technique using the same size donor-recipient button may provide better visual outcomes particularly in patients with KC.

Validation of Na,K-ATPase pump function of corneal endothelial cells for corneal regenerative medicine.

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Hatou, Shin; Higa, Kazunari; Inagaki, Emi; Yoshida, Satoru; Kimura, Erika; Hayashi, Ryuhei; Tsujikawa, Motokazu; Tsubota, Kazuo; Nishida, Kohji; Shimmura, Shigeto

2013-12-01

Tissue-engineering approaches to cultivate corneal endothelial cells (CECs) or induce CECs from stem cells are under investigation for the treatment of endothelial dysfunction. Before clinical application, a validation method to determine the quality of these cells is required. In this study, we quantified the endothelial pump function required for maintaining the corneal thickness using rabbit CECs (RCECs) and a human CEC line (B4G12). The potential difference of RCECs cultured on a permeable polyester membrane (Snapwell), B4G12 cells on Snapwell, or B4G12 cells on a collagen membrane (CM6) was measured by an Ussing chamber system, and the effect of different concentrations of ouabain (Na,K-ATPase specific inhibitor) was obtained. A mathematical equation derived from the concentration curve revealed that 2 mM ouabain decreases pump function of RCECs to 1.0 mV, and 0.6 mM ouabain decreases pump function of B4G12 on CM6 to 1.0 mV. Ouabain injection into the anterior chamber of rabbit eyes at a concentration of pump function >1.0 mV is required to maintain the corneal thickness. These results can be used for standardization of CEC pump function and validation of tissue-engineered CEC sheets for clinical use.

Wine and endothelial function.

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Caimi, G; Carollo, C; Lo Presti, R

2003-01-01

In recent years many studies have focused on the well-known relationship between wine consumption and cardiovascular risk. Wine exerts its protective effects through various changes in lipoprotein profile, coagulation and fibrinolytic cascades, platelet aggregation, oxidative mechanisms and endothelial function. The last has earned more attention for its implications in atherogenesis. Endothelium regulates vascular tone by a delicate balancing among vasorelaxing (nitric oxide [NO]) and vasoconstrincting (endothelins) factors produced by endothelium in response to various stimuli. In rat models, wine and other grape derivatives exerted an endothelium-dependent vasorelaxing capacity especially associated with the NO-stimulating activity of their polyphenol components. In experimental conditions, reservatrol (a stilbene polyphenol) protected hearts and kidneys from ischemia-reperfusion injury through antioxidant activity and upregulation of NO production. Wine polyphenols are also able to induce the expression of genes involved in the NO pathway within the arterial wall. The effects of wine on endothelial function in humans are not yet clearly understood. A favorable action of red wine or dealcoholized wine extract or purple grape juice on endothelial function has been observed by several authors, but discrimination between ethanol and polyphenol effects is controversial. It is, however likely that regular and prolonged moderate wine drinking positively affects endothelial function. The beneficial effects of wine on cardiovascular health are greater if wine is associated with a healthy diet. The most recent nutritional and epidemiologic studies show that the ideal diet closely resembles the Mediterranean diet.

Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

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Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2016-12-15

Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

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Miroslav Radenkovic

2016-01-01

Full Text Available The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

cGMP and nitric oxide modulate thrombin-induced endothelial permeability : Regulation via different pathways in human aortic and umbilical vein endothelial cells

NARCIS (Netherlands)

Draijer, R.; Atsma, D.E.; Laarse, A. van der; Hinsbergh, V.W.M. van

1995-01-01

Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial.

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Felau, Sheylla M; Sales, Lucas P; Solis, Marina Y; Hayashi, Ana Paula; Roschel, Hamilton; Sá-Pinto, Ana Lúcia; Andrade, Danieli Castro Oliveira De; Katayama, Keyla Y; Irigoyen, Maria Claudia; Consolim-Colombo, Fernanda; Bonfa, Eloisa; Gualano, Bruno; Benatti, Fabiana B

2018-01-01

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n  = 11) or n-3 PUFA (ω-3, n  = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p  = 0.06, ES = 0.9; and +23 vs. -22%, p  = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels ( p  > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p  = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p  = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p  = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial

Science.gov (United States)

Felau, Sheylla M.; Sales, Lucas P.; Solis, Marina Y.; Hayashi, Ana Paula; Roschel, Hamilton; Sá-Pinto, Ana Lúcia; Andrade, Danieli Castro Oliveira De; Katayama, Keyla Y.; Irigoyen, Maria Claudia; Consolim-Colombo, Fernanda; Bonfa, Eloisa; Gualano, Bruno; Benatti, Fabiana B.

2018-01-01

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. −12%, p = 0.06, ES = 0.9; and +23 vs. −22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (−4 vs. +45%, p = 0.04, ES = −0.9) and tumor necrosis factor (−13 vs. +0.3%, p = 0.04, ES = −0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = −0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an

Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation.

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Jo-Watanabe, Airi; Ohse, Takamoto; Nishimatsu, Hiroaki; Takahashi, Masao; Ikeda, Yoichiro; Wada, Takehiko; Shirakawa, Jun-ichi; Nagai, Ryoji; Miyata, Toshio; Nagano, Tetsuo; Hirata, Yasunobu; Inagi, Reiko; Nangaku, Masaomi

2014-06-01

Endothelial dysfunction is a major contributor to cardiovascular disease (CVD), particularly in elderly people. Studies have demonstrated the role of glycation in endothelial dysfunction in nonphysiological models, but the physiological role of glycation in age-related endothelial dysfunction has been poorly addressed. Here, to investigate how vascular glycation affects age-related endothelial function, we employed rats systemically overexpressing glyoxalase I (GLO1), which detoxifies methylglyoxal (MG), a representative precursor of glycation. Four groups of rats were examined, namely young (13 weeks old), mid-age (53 weeks old) wild-type, and GLO1 transgenic (WT/GLO1 Tg) rats. Age-related acceleration in glycation was attenuated in GLO1 Tg rats, together with lower aortic carboxymethyllysine (CML) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Age-related impairment of endothelium-dependent vasorelaxation was attenuated in GLO1 Tg rats, whereas endothelium-independent vasorelaxation was not different between WT and GLO1 Tg rats. Nitric oxide (NO) production was decreased in mid-age WT rats, but not in mid-age GLO1 Tg rats. Age-related inactivation of endothelial NO synthase (eNOS) due to phosphorylation of eNOS on Thr495 and dephosphorylation on Ser1177 was ameliorated in GLO1 Tg rats. In vitro, MG increased phosphorylation of eNOS (Thr495) in primary human aortic endothelial cells (HAECs), and overexpression of GLO1 decreased glycative stress and phosphorylation of eNOS (Thr495). Together, GLO1 reduced age-related endothelial glycative and oxidative stress, altered phohphorylation of eNOS, and attenuated endothelial dysfunction. As a molecular mechanism, GLO1 lessened inhibitory phosphorylation of eNOS (Thr495) by reducing glycative stress. Our study demonstrates that blunting glycative stress prevents the long-term impact of endothelial dysfunction on vascular aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

International Nuclear Information System (INIS)

Li, Zhijuan; Cheng, Jianxin; Wang, Liping

2015-01-01

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.

Tumor and Endothelial Cell Hybrids Participate in Glioblastoma Vasculature

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Soufiane El Hallani

2014-01-01

Full Text Available Background. Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM. Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM. Materials and Methods. We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact. Results. In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF. By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation. Conclusion. A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.

Resveratrol induces mitochondrial biogenesis in endothelial cells.

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Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

2009-07-01

Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

Papillary endothelial hyperplasia in angiokeratoma.

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Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

2003-01-01

Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

Clinical implications for Vascular Endothelial Growth Factor in the lung: friend or foe?

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Gourgoulianis Konstantinos I

2006-10-01

Full Text Available Abstract Vascular endothelial growth factor (VEGF is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.

Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

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Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

2015-12-01

Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

Adhesion and endothelialization of endothelial cells on the surface of endovascular stents by the novel rotational culture of cells

International Nuclear Information System (INIS)

Tang Chaojun; Wang Guixue; Cao Yi; Wu Xue; Xie Xiang; Xiao Li

2008-01-01

Recent researches indicate that the initial event in the implantation of endovascular stents involves mechanical injury to the vessel wall. Confluent endothelialization of vascular grafts in vitro before implantation has been suggested as a way to reduce injury of the blood vessel. The purpose of this study is to establish a useful way to improve the adhesion of endothelial cells and accelerate endothelialization on the surface of endovascular stents by a novel rotational culture device. Numerical simulation was used to predict the shear stress on the surface of stents. The number of cellular adhesion was calculated by cell counting, the cell growth was observed by scanning electron microscope and fluorescence microscope. Numerical simulation results showed that the stents was exposed to shear stress of 2.66 x 10 -3 to 8.88 x 10 -2 Pa. Rotational culture of human umbilical vein endothelial cells could enhance the adhesion of cells and accelerate endothelialization on the surface of stents when the culture conditions for EC adhesion were intermediate rotation speed, higher dynamic incubation times, lower cell densities

Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

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Stanhewicz, Anna E; Kenney, W Larry

2017-01-01

Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms.

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Cláudia Torres

Full Text Available BACKGROUND: Circulating endothelial cells (CEC may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. OBJECTIVES: To quantify CEC and CEP in patients with venous thromboembolism (VTE and with myeloproliferative neoplasms (MPN, to characterize the CEC for the expression of activation (CD54, CD62E and procoagulant (CD142 markers and to investigate whether they correlate with other clinical and laboratory data. PATIENTS AND METHODS: Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. RESULTS: We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls, whereas only patients with VTE had increased numbers of CD142+ and CD54+ CEC. Moreover, the numbers of total and CD62+ CEC correlated positively with the white blood cells (WBC counts in both groups of patients, while the numbers of CEP correlated positively with the WBC counts only in patients with MPN. In addition, in patients with VTE a positive correlation was found between the numbers of CD54+ CEC and the antithrombin levels, as well as between the CD142+ CEC counts and the number of thrombotic events. CONCLUSIONS: Our study suggests that CEC counts may reveal endothelial injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes depending on the disease status.

Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

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Jiamin Li

2018-02-01

Full Text Available Background/Aims: Endothelial-mesenchymal transition (EndMT has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H2O2 (100 µm for seven days. Human aortic endothelial cells (HAECs were exposed to H2O2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM deposition that is associated with matrix metallopeptidase (MMP proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.

Self-reported racial discrimination and endothelial reactivity to acute stress in women.

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Wagner, Julie A; Tennen, Howard; Finan, Patrick H; Ghuman, Nimrta; Burg, Matthew M

2013-08-01

This study investigated the effect of self-reported racial discrimination on endothelial responses to acute laboratory mental stress among post-menopausal women. One-hundred thirteen women (n = 94 self-identified as White and n = 19 self-identified as racial/ethnic minority), 43% with type 2 diabetes, reported lifetime experiences of racial/ethnic discrimination. Repeated assessments of flow-mediated dilation were performed at baseline, immediately after 5 min of mental arithmetic and at 20-min recovery. Both White and racial/ethnic minority women reported lifetime discrimination, with rates significantly higher among minorities. Self-reported lifetime discrimination was associated with attenuated flow-mediated dilation at recovery. Confounding variables, including clinical characteristics, mood, personality traits, other life stressors and general distress, did not better account for the effect of racial discrimination. Neither race/ethnicity nor diabetes status moderated the effect. The perceived stressfulness of the mental arithmetic was not associated with the endothelial response. In conclusion, self-reported lifetime discrimination is associated with attenuated endothelial recovery from acute mental stress. Elucidating the effects of discrimination and the biological mechanisms through which it affects the vasculature may suggest interventions to improve health. Copyright © 2012 John Wiley & Sons, Ltd.

Expression Profiling of Genes Related to Endothelial Cells Biology in Patients with Type 2 Diabetes and Patients with Prediabetes

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Sara Moradipoor

2016-01-01

Full Text Available Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT2 Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.

Nipah virus infection and glycoprotein targeting in endothelial cells

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Maisner Andrea

2010-11-01

Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

Optimization of human corneal endothelial cell culture: density dependency of successful cultures in vitro.

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Peh, Gary S L; Toh, Kah-Peng; Ang, Heng-Pei; Seah, Xin-Yi; George, Benjamin L; Mehta, Jodhbir S

2013-05-03

Global shortage of donor corneas greatly restricts the numbers of corneal transplantations performed yearly. Limited ex vivo expansion of primary human corneal endothelial cells is possible, and a considerable clinical interest exists for development of tissue-engineered constructs using cultivated corneal endothelial cells. The objective of this study was to investigate the density-dependent growth of human corneal endothelial cells isolated from paired donor corneas and to elucidate an optimal seeding density for their extended expansion in vitro whilst maintaining their unique cellular morphology. Established primary human corneal endothelial cells were propagated to the second passage (P2) before they were utilized for this study. Confluent P2 cells were dissociated and seeded at four seeding densities: 2,500 cells per cm2 ('LOW'); 5,000 cells per cm2 ('MID'); 10,000 cells per cm2 ('HIGH'); and 20,000 cells per cm2 ('HIGH(×2)'), and subsequently analyzed for their propensity to proliferate. They were also subjected to morphometric analyses comparing cell sizes, coefficient of variance, as well as cell circularity when each culture became confluent. At the two lower densities, proliferation rates were higher than cells seeded at higher densities, though not statistically significant. However, corneal endothelial cells seeded at lower densities were significantly larger in size, heterogeneous in shape and less circular (fibroblastic-like), and remained hypertrophic after one month in culture. Comparatively, cells seeded at higher densities were significantly homogeneous, compact and circular at confluence. Potentially, at an optimal seeding density of 10,000 cells per cm2, it is possible to obtain between 10 million to 25 million cells at the third passage. More importantly, these expanded human corneal endothelial cells retained their unique cellular morphology. Our results demonstrated a density dependency in the culture of primary human corneal endothelial

Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

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Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

2015-01-01

Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

Endothelial actions of atrial and B-type natriuretic peptides.

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Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

Qidantongmai Protects Endothelial Cells Against Hypoxia-Induced ...

African Journals Online (AJOL)

induced damage. The ability of QDTM to modulate the serum VEGF-A level may play an important role in its effects on endothelial cells. Key words: Traditional Chinese Medicine, human umbilical vein endothelial cells, hypoxia, VEGF ...

Infection of endothelial cells by common human viruses.

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Friedman, H M

1989-01-01

Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

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Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

2014-01-01

The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells.

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Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea

2017-01-01

Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

Spring-action Apparatus for Fixation of Eyeball (SAFE): a novel, cost-effective yet simple device for ophthalmic wet-lab training.

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Ramakrishnan, Seema; Baskaran, Prabu; Fazal, Romana; Sulaiman, Syed Mohammad; Krishnan, Tiruvengada; Venkatesh, Rengaraj

2016-10-01

Achieving a formed and firm eyeball which is stably fixed in a holding device is a major challenge of surgical wet-lab training. Our innovation, the 'Spring-action Apparatus for Fixation of Eyeball (SAFE)' is a robust, simple and economical device to solve this problem. It consists of a hollow iron cylinder to which a spring-action syringe is attached. The spring-action syringe generates vacuum and enables reliable fixation of a human or animal cadaveric eye on the iron cylinder. The rise in intraocular pressure due to vacuum fixation can be varied as per need or nature of surgery being practised. A mask-fixed version of this device is also designed to train surgeons for appropriate hand positioning. An experienced surgeon performed various surgeries including manual small incision cataract surgery (MSICS), phacoemulsification, laser in situ keratomileusis (LASIK), femtosecond LASIK docking, Descemet's stripping endothelial keratoplasty, deep anterior lamellar keratoplasty, penetrating keratoplasty and trabeculectomy on this device, while a trainee surgeon practised MSICS and wound suturing. Skill-appropriate comfort level was much higher with SAFE than with conventional globe holders for both surgeons. Due to its stability, pressure adjustability, portability, cost-efficiency and simplicity, we recommend SAFE as the basic equipment for every wet lab. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells.

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Masahiro Myojo

Full Text Available Because endothelial nitric oxide synthase (eNOS has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177 in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172 and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP. Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

Magnetizable stent-grafts enable endothelial cell capture

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Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients.

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Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian

2010-02-01

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p nailfold capillaroscopy (r = 0.458, p nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

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Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

EFFECT OF HIGH-INTENSITY EXERCISE ON ENDOTHELIAL FUNCTION IN PATIENTS WITH T2DM

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Carlos Alberto da Silva

2016-04-01

Full Text Available Introduction: Diabetes mellitus is the most common metabolic disease worldwide. Endothelial dysfunction characteristic of these patients is one of the major risk factors for atherosclerosis. Early diagnosis of endothelial dysfunction is essential for the treatment especially of non-invasive manner, such as flow mediated dilation. Physical exercise is capable of generating beneficial adaptations may improve endothelial function. Objective: Identify the effect of physical exercise, using the clinical technique of ultrasound in the assessment of the endothelial function of patients with metabolic syndrome or type 2 diabetes mellitus. Methods: Thirty-one patients with type 2 diabetes mellitus or metabolic syndrome were studied, with a mean age (± SD of 58±6 years, randomized into three groups. The training was performed for 50 minutes, four times a week. Before and after six weeks of training, subjects performed the endurance test and a study of the endothelial function of the brachial artery by high-resolution ultrasound. Results: After hyperemia, the percentage of arterial diameter was significantly higher for the high-intensity group (HI before = 2.52±2.85mm and after = 31.81±12.21mm; LI before = 3.23±3.52mm and after = 20.61±7.76mm; controls before = 3.56±2.33mm and after = 2.43±2.14mm; p<0.05. Conclusions: The high-intensity aerobic training improved the vasodilatation response-dependent endothelium, recorded by ultrasound, in patients with metabolic syndrome and type 2 diabetes.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

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Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

2017-11-01

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

Essential Role of Endothelial Notch1 in Angiogenesis

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Limbourg, Florian P.; Takeshita, Kyosuke; Radtke, Freddy; Bronson, Roderick T.; Chin, Michael T.; Liao, James K.

2009-01-01

Background Notch signaling influences binary cell fate decisions in a variety of tissues. The Notch1 receptor is widely expressed during embryogenesis and is essential for embryonic development. Loss of global Notch1 function results in early embryonic lethality, but the cell type responsible for this defect is not known. Here, we identify the endothelium as the primary target tissue affected by Notch1 signaling. Methods and Results We generated an endothelium-specific deletion of Notch1 using Tie2Cre and conditional Notch1flox/flox mice. Mutant embryos lacking endothelial Notch1 died at approximately embryonic day 10.5 with profound vascular defects in placenta, yolk sac, and embryo proper, whereas heterozygous deletion had no effect. In yolk sacs of mutant embryos, endothelial cells formed a primary vascular plexus indicative of intact vasculogenesis but failed to induce the secondary vascular remodeling required to form a mature network of well-organized large and small blood vessels, which demonstrates a defect in angiogenesis. These vascular defects were also evident in the placenta, where blood vessels failed to invade the placental labyrinth, and in the embryo proper, where defective blood vessel maturation led to pericardial and intersomitic hemorrhage. Enhanced activation of caspase-3 was detected in endothelial and neural cells of mutant mice, which resulted in enhanced apoptotic degeneration of somites and the neural tube. Conclusions These findings recapitulate the vascular phenotype of global Notch1-/- mutants and indicate an essential cell-autonomous role of Notch1 signaling in the endothelium during vascular development. These results may have important clinical implications with regard to Notch1 signaling in adult angiogenesis. PMID:15809373

Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy

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Mees, Barend; Récalde, Alice; Loinard, Céline; Tempel, Dennie; Godinho, Marcia; Vilar, José; van Haperen, Rien; Lévy, Bernard; de Crom, Rini; Silvestre, Jean-Sébastien

2011-01-01

Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease. PMID:21224043

Aging-associated oxidized albumin promotes cellular senescence and endothelial damage

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Luna C

2016-02-01

Full Text Available Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

Signaling hierarchy regulating human endothelial cell development

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Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

Late occurrence of granular dystrophy in bilateral keratoconus: Penetrating keratoplasty and long-term follow-up

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Varsha M Rathi

2011-01-01

Full Text Available We report a rare case of keratoconus with granular dystrophy with a follow-up of two decades, documenting the sequential presentation of two diseases confirmed by histology and genetic studies. A 13-year-old boy was diagnosed in 1988 with keratoconus in both eyes (BE based on slit-lamp biomicroscopy findings of corneal ectasia in BE accompanied by Fleischer′s ring, Vogt′s striae, a small, old, healed hydrops. The left eye (LE had central corneal thinning and scar in the central area involving the mid and posterior stroma secondary to healed hydrops. Penetrating keratoplasty (PKP was advised. The boy was lost to follow-up till 1991 and presented with white, dot-like opacities in the central cornea in the RE only, suggestive of granular corneal dystrophy. Similar findings of white, dot-like opacities were noted in the LE in 1995 and the patient subsequently underwent PKP in BE. Histopathology of corneal buttons confirmed the presence of patchy, crystal-like orange deposits, which stained bright red with Masson′s trichrome. Mutational analysis of the TGFBI gene in patient′s DNA revealed a heterozygous mutation corresponding to a change in Arg555Trp in the keratoepithelin protein. Granular dystrophy recurred after 8 years in the RE.

Endothelial adhesion molecules and leukocyte integrins in preeclamptic patients.

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Haller, H; Ziegler, E M; Homuth, V; Drab, M; Eichhorn, J; Nagy, Z; Busjahn, A; Vetter, K; Luft, F C

1997-01-01

Endothelial cell activation is important in the pathogenesis of preeclampsia; however, the nature of the activation is unknown. We investigated 22 patients with preeclampsia. 29 normotensive pregnancies, and 18 nonpregnant women to test the hypothesis that serum from preeclamptic patients induces expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) and stimulates intracellular free calcium concentrations [Ca2+]i in cultured endothelial cells. We then asked whether the corresponding integrin adhesive counter receptors lymphocyte function-associated antigen-1 (CD11a/CD18), macrophage-1 antigen (CD11b/CD18), p150,95 (CD11c/CD18), and very late activation antigen-4 (CD49/CD29) are increased in patients with preeclampsia. In the pregnant women, the measurements were conducted both before and after delivery. Integrin expression was measured by fluorescent antibody cell sorting analysis using monoclonal antibodies. ICAM-1 and VCAM-1 were analyzed on endothelial cells by enzyme-linked immunosorbent assay. [Ca2+]i was measured with fura 2. Serum from preeclamptic patients increased endothelial cell ICAM-1 expression but not VCAM-1 expression. Preeclamptic patients' serum also increased [Ca2+]i in endothelial cells compared with serum from normal nonpregnant or normal pregnant women. Endothelial cell [Ca2+]i concentrations were correlated with the ICAM-1 expression in preeclamptic patients (r = .80, P preclampsia and normal pregnancy compared with the nonpregnant state. The expression decreased significantly after delivery in both groups. Our results demonstrate that serum from preeclamptic women induces increased ICAM-1 surface expression on endothelial cells, while the expression of the integrin counterreceptors was not different. The effect on endothelial cells may be related to an increase in [Ca2+]i. The effect on cultured endothelial cells and the rapid decrease after delivery suggests the presence of a circulating serum

Corneal Transplantation in Auckland, New Zealand, 1999-2009: Indications, Patient Characteristics, Ethnicity, Social Deprivation, and Access to Services.

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Crawford, Alexandra Z; McKelvie, James; Craig, Jennifer P; McGhee, Charles N J; Patel, Dipika V

2017-05-01

To analyze characteristics and indications for corneal transplantation in patients undergoing penetrating, lamellar, and endothelial keratoplasty in Auckland, New Zealand (NZ). Corneal transplantation data from the NZ National Eye Bank and hospital records of corneal transplant recipients in the Auckland region from January 1, 2000, to December 31, 2009, were collated. Patient demographics, preoperative diagnosis, indication, ocular and medical history, visual acuity, deprivation index, and access to transplantation surgery were analyzed. A total of 941 corneal transplants involving 770 patients were included for analysis. Mean age was 46 years. Age and ethnicity varied according to the transplant indication. A male preponderance and disproportionally high rates of Māori and Pacific ethnicity with a mean age of 30 years were observed in transplants for keratoconus. A total of 67.2% of corneal transplants were completed in the public health system and were associated with higher levels of deprivation than those completed in private facilities. Preoperative visual acuity varied according to the transplant type and indication. The most common clinical indication for corneal transplantation was keratoconus (41.3%), followed by repeat transplantation (21.0%). There was no significant change in the relative proportion of transplant indications in any year over the duration of this study (P = 0.41). A contralateral corneal transplant was present in 24.4% and glaucoma in 12.8% of penetrating keratoplasty recipients. Keratoconus is the leading indication for corneal transplantation in Auckland, NZ, and involves a disproportionately high rate of Māori and Pacific transplant recipients with a male preponderance and comparatively low mean age at the time of surgery.

Syncytin is involved in breast cancer-endothelial cell fusions

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Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

2006-01-01

Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

Differentiation state determines neural effects on microvascular endothelial cells

International Nuclear Information System (INIS)

Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

2012-01-01

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

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Caterina Oriana Aragona

2016-01-01

Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

Consumption of High-Polyphenol Dark Chocolate Improves Endothelial Function in Individuals with Stage 1 Hypertension and Excess Body Weight

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Lívia de Paula Nogueira

2012-01-01

Full Text Available Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m2. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical. Results. Twenty participants (10 men completed the study. Comparison of pre-post intervention revealed that (1 there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2 the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P=0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells.

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Lu Dai

Full Text Available Phosphorylation of sphingosine by sphingosine kinases (SphK1 and SphK2 generates sphingosine-1-phosphate (S1P, a bioactive sphingolipid which promotes cancer cell survival and tumor progression in vivo. We have recently reported that targeting SphK2 induces apoptosis for human primary effusion lymphoma (PEL cell lines infected by the Kaposi's sarcoma-associated herpesvirus (KSHV, and this occurs in part through inhibition of canonical NF-κB activation. In contrast, pharmacologic inhibition of SphK2 has minimal impact for uninfected B-cell lines or circulating human B cells from healthy donors. Therefore, we designed additional studies employing primary human endothelial cells to explore mechanisms responsible for the selective death observed for KSHV-infected cells during SphK2 targeting. Using RNA interference and a clinically relevant pharmacologic approach, we have found that targeting SphK2 induces apoptosis selectively for KSHV-infected endothelial cells through induction of viral lytic gene expression. Moreover, this effect occurs through repression of KSHV-microRNAs regulating viral latency and signal transduction, including miR-K12-1 which targets IκBα to facilitate activation of NF-κB, and ectopic expression of miR-K12-1 restores NF-κB activation and viability for KSHV-infected endothelial cells during SphK2 inhibition. These data illuminate a novel survival mechanism and potential therapeutic target for KSHV-infected endothelial cells: SphK2-associated maintenance of viral latency.

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering.

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Jui-Yang Lai

Full Text Available Hyaluronic acid (HA is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function.

Delayed Complications and Long-Term Management of Sulfur Mustard Poisoning: A Narrative Review of Recent Advances by Iranian Researchers Part ІІ: Clinical Management and Therapy

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Leila Etemad

2018-05-01

Full Text Available The present study aimed to review and discuss the recommended and recently suggested protocols by Iranian researchers for a long-term treatment of delayed complications of sulfur mustard (DCSM in veterans. As indicated clinically, patients who suffer from delayed ocular complications of sulfur mustard (DOCS benefit from treatments for dry eyes, therapeutic contact lenses, amniotic membrane transplantation; blepharorrhaphy, tarsorrhaphy, limbal stem cell transplantation; corneal transplantation, topical steroids, and immunosuppressive. In spite of penetrating keratoplasty, lamellar keratoplasty and keratolimbal allograft had a good long-term survival. Delayed respiratory complications (DRCS are the most common effects and life-threatening in Iranian veterans. The recommended treatment protocols include regular clinical evaluations, respiratory physiotherapy and rehabilitation, N-acetyl cysteine; warm humidified air, long-acting 2-agonists, and inhaled corticosteroids. Azithromycin has also been effective in improving clinical conditions, pulmonary function tests, inflammatory indexes, and life quality of the veterans. Interferon gamma (IFN-γ and helium: oxygen combination were also used in severe DRCS with good results. Some of the delayed cutaneous complications (DCCS such as itching affects the quality of life of victims. Regular but not frequent showering and bathing, applying sunscreen compounds, topical corticosteroids, and systemic antihistamines reduce the problems of DCCS patients. Several compounds such as capsaicin cream, pimecrolimus, IFN-γ, phenol-menthol; Aloe vera/olive oil cream, cetirizine, doxepine, and hydroxyzine were evaluated in DCCS patients with some benefits. The physicians in charge of veterans emphasize the importance of a healthy lifestyle, appropriate financial/social/cultural supports, and a degree of reassurance and supportive care on the clinical improvement of patients.

The role of corneal endothelial morphology in graft assessment and prediction of endothelial cell loss during organ culture of human donor corneas.

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Hermel, Martin; Salla, Sabine; Fuest, Matthias; Walter, Peter

2017-03-01

Endothelial assessment is crucial in the release of corneas for grafting. We retrospectively analysed the role of endothelial morphology parameters in predicting endothelial cell loss during organ culture. Human donor corneas were cultured in minimal essential medium with 2% fetal calf serum and antibiotics. Initial endothelial morphology was assessed microscopically using score parameters polymegethism (POL), pleomorphism (PLE), granulation (GRA), vacuolization (VAC), segmentation of cell membranes (SEG), Descemet's folds (DF), trypan blue-positive cells (TBPC) and endothelial cell-free areas (ECFA). Some corneas were primarily rejected based on endothelial assessment. Endothelial cell density (ECD) was assessed at the beginning (I-ECD) and end of culture. Corneas were then placed in dehydration medium (as above + 5% dextran 500). In a subgroup, ECD was reassessed after dehydration. Endothelial cell loss during culture (ECL@Culture) and culture+dehydration (ECL-Culture&Dehydration) were calculated. Data were given as mean ± SD and analysed using multiple linear and logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. I-ECD was 2812 ± 360/mm 2 (n = 2356). The decision to reject a cornea due to endothelial assessment was associated negatively with I-ECD (OR = 0.77/100 cells, CI 0.7-0.82) and positively with ECFA (OR = 2.7, CI 1.69-4.35), SEG (OR =1.3, CI 1.01-1.68) and donor age (OR = 1.26/decade, CI 1.33-1.41). ECL@Culture was 153 ± 201/mm 2 (n = 1277), ECL@Culture&Dehydration was 169 ± 183/mm 2 (n = 918). ECL@Culture was associated positively with donor age, I-ECD, GRA and TBPC, and negatively with PLE, and DF. ECL@Culture&Dehydration was associated positively with age, sex, initial ECD, POL, PLE, VAC and TBPC. Morphological parameters displayed associations with the exclusion of corneas from culture and with endothelial cell loss. Appropriate parameter selection for screening purposes may help improve

The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

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Magdalena Sternak

2018-04-01

Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

5-Hydroxytryptamine 4 Receptor in the Endothelial Cells

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Profirovic, Jasmina; Vardya, Irina; Voyno-Yasenetskaya, Tatyana

2006-01-01

39 5-HYDROXYTRYPTAMINE 4 RECEPTOR IN THE ENDOTHELIAL CELLS. J. Profirovic, I. Vardya, T. Voyno-Yasenetskaya, Department of Pharmacology, University of Illinois at Chicago, Chicago, IL. Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter that regulates multiple events in the ce......39 5-HYDROXYTRYPTAMINE 4 RECEPTOR IN THE ENDOTHELIAL CELLS. J. Profirovic, I. Vardya, T. Voyno-Yasenetskaya, Department of Pharmacology, University of Illinois at Chicago, Chicago, IL. Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter that regulates multiple events...... gap formation in HUVECs. We are currently investigating the mechanism underlying 5-HT4 receptor-induced actin cytoskeleton changes in the endothelial cells. These data suggest that by activating 5-HT4 receptor, serotonin could be involved in regulation of actin cytoskeleton dynamics in the endothelial...

Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

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Della Corte, Vittoriano; Tuttolomondo, Antonino; Pecoraro, Rosaria; Di Raimondo, Domenico; Vassallo, Valerio; Pinto, Antonio

2016-01-01

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to

Endothelial Function in Migraine With Aura – A Systematic Review

DEFF Research Database (Denmark)

Butt, Jawad H; Franzmann, Ulriche; Kruuse, Christina

2015-01-01

in migraineurs, and several studies on endothelial markers in the areas of inflammation, oxidative stress, and coagulation found increased endothelial activation in migraineurs, particularly in MA. One study, assessing cerebral endothelial function using transcranial Doppler sonography, reported lower...

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

Energy Technology Data Exchange (ETDEWEB)

Li, Zhijuan, E-mail: zjlee038@163.com; Cheng, Jianxin; Wang, Liping

2015-10-30

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.

Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction.

Science.gov (United States)

Stühlinger, Markus C; Stanger, Olaf

2005-02-01

Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated plasma homocysteine levels seems to be clinically relevant, since the total cardiovascular risk of hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia or smoking. There is substantial evidence for impairment of endothelial function in human and animal models of atherosclerosis, occurring even before development of overt plaques. Interestingly endothelial dysfunction appears to be a sensitive indicator of the process of atherosclerotic lesion development and predicts future vascular events. NO is the most potent endogenous vasodilator known. It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease. Substances leading to impaired endothelial function as a consequence of reduced NO generation are endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating evidence from animal and human studies that ADMA, endothelial function and homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA associated with impaired endothelium-dependent relaxation were found in chronic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent endothelial dysfunction can be successfully treated by application of folate and B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced endothelial dysfunction, another way of preventing vascular disease in patients with elevated homocyst

Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

Science.gov (United States)

Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

2011-04-01

Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Acanthamoeba Keratitis at the King Khaled Eye Specialist Hospital

International Nuclear Information System (INIS)

Al-Mezaine, H.; Al-Muteb, M.; Al-Motowa, S.; Wagoner, M. D.

2005-01-01

To quantify the number of cases and clinical courses of Acanthamoeba keratitis treated at the King Khaled Eye Specialist Hospital (KKESH) between December 1982 and May 2005, and to review their clinical course and response to medical and surgical therapy. Retrospective review of medical records of all patients with Acanthamoeba keratitis diagnosed by the KKESH Microbiology or Pathology or Pathology Laboratory since the opening of the hospital. During a period of over 22 years, only six cases of confirmed. Acanthamoeba keratitis were diagnosedand treated at KKESH. In two cases the diagnosis was made by corneal biopsy, while four cases required examination of a histopathology specimen obtained at the time of therapeutic keratoplasty to establish the diagnosis. One eye was cured by medical therapy, while five eyes required one (4eyes) or two (1 eye) therapeutic penetrating keratoplasty (PKP) to achieve a clinical cure. Three eyes achieved good visual acuity (20/40, 20/50, 20/60), one eye achieved fair visual acuity (20/160), and two eyes suffered profound visual loss (hand motions). The incidence of Acanthamoeba keratitis may be less in Saudi Arabia than reported in Western countries although the clinical is similarly complicated, with most cases requiring therapeutic keratoplasty for definitive education of the organism. (author)

Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Stark, Christopher, E-mail: Christopher.stark@uvmhealth.org [University of Vermont Medical Center, Department of Radiology (United States); Olsen, Daniel [Mayo Clinic, Department of Pathology (United States); Morris, Christopher [University of Vermont Medical Center, Department of Radiology (United States); Bertges, Daniel [University of Vermont Medical Center, Department of Surgery (United States); Najarian, Kenneth [University of Vermont Medical Center, Department of Radiology (United States)

2016-11-15

Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodality imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.

Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

International Nuclear Information System (INIS)

Stark, Christopher; Olsen, Daniel; Morris, Christopher; Bertges, Daniel; Najarian, Kenneth

2016-01-01

Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodality imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.

HERPES VIRUS CONTAMINATION OF DONOR’S TISSUE AS A POTENTIAL ETIOLOGY OF CORNEAL GRAFT DISEASE AFTER PENETRATING KERATOPLASTY

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E. A. Mironkova

2012-01-01

Full Text Available We present the study of outcomes of PCR-diagnostics directed on detection of DNA of herpes-family viruses in donor’s corneal tissues taken during penetrating keratoplasty (PK. In total, there were 46 patients, who under- went PKs. They were followed up from 14 days till 12 months. PCR-research of fragments of a donor cornea re- vealed existence of DNA in 21.7%. The retrospective analysis showed that in the presence of herpes-virus DNA in donor’s cornea is the risk factor of postoperative complications development and increases the rejection rate 2–3 times, reaching 100% – 70%. Thus the high risk of graft failures remains associated not only with the system immunosupressive therapy which is usually considered as the precondition of activization of chronic infections, but also in the absence of that. It gives the ground to conclude that preoperative preparation of a donor material, especially «fresh» corneas, should include expanded PCR-diagnostics on herpes-viruses and its obligatory dis- carding in cases of positive tests. 

Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

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Cristina Espinosa-Díez

2018-04-01

Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

Insomnia and endothelial function - the HUNT 3 fitness study.

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Linn B Strand

Full Text Available BACKGROUND: Insomnia is associated with increased risk of coronary heart disease (CHD, but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. METHODS: A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD derived from the brachial artery. RESULTS: We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p = 0.03. CONCLUSIONS: This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.

Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF

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Francesco Vieceli Dalla Sega

2018-04-01

Full Text Available Ticagrelor is one of the most powerful P2Y12 inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD and Chronic Obstructive Pulmonary Disease (COPD undergoing percutaneous coronary intervention (PCI, treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608. In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in vitro in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.

Asymmetric Dimethylarginine Plasma Levels and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients

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Francesco Perticone

2012-10-01

Full Text Available It is now well established that major risk factors for cardiovascular diseases (CVD impact upon endothelial function by decreasing nitric oxide (NO bioavailability. Asymmetric dimethylarginine (ADMA, an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF. In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001 and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001. In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications.

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Science.gov (United States)

Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

2010-01-01

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo.

Science.gov (United States)

Venalis, Paulius; Maurer, Britta; Akhmetshina, Alfiya; Busch, Nicole; Dees, Clara; Stürzl, Michael; Zwerina, Jochen; Jüngel, Astrid; Gay, Steffen; Schett, Georg; Distler, Oliver; Distler, Jörg H W

2009-10-01

Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.

Hydrogen sulfide metabolism regulates endothelial solute barrier function

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Shuai Yuan

2016-10-01

Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

Science.gov (United States)

Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

2015-09-01

Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

The glutathione mimic ebselen inhibits oxidative stress but not endoplasmic reticulum stress in endothelial cells.

Science.gov (United States)

Ahwach, Salma Makhoul; Thomas, Melanie; Onstead-Haas, Luisa; Mooradian, Arshag D; Haas, Michael J

2015-08-01

Reactive oxygen species are associated with cardiovascular disease, diabetes, and atherosclerosis, yet the use of antioxidants in clinical trials has been ineffective at improving outcomes. In endothelial cells, high-dextrose-induced oxidative stress and endoplasmic reticulum stress promote endothelial dysfunction leading to the recruitment and activation of peripheral blood lymphocytes and the breakdown of barrier function. Ebselen, a glutathione peroxidase 1 (GPX1) mimic, has been shown to improve β-cell function in diabetes and prevent atherosclerosis. To determine if ebselen inhibits both oxidative stress and endoplasmic reticulum (ER) stress in endothelial cells, we examined its effects in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) with and without high-dextrose. Oxidative stress and ER stress were measured by 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence and ER stress alkaline phosphatase assays, respectively. GPX1 over-expression and knockdown were performed by transfecting cells with a GPX1 expression construct or a GPX1-specific siRNA, respectively. Ebselen inhibited dextrose-induced oxidative stress but not ER stress in both HUVEC and HCAEC. Ebselen also had no effect on tunicamycin-induced ER stress in HCAEC. Furthermore, augmentation of GPX1 activity directly by sodium selenite supplementation or transfection of a GPX1 expression plasmid decreased dextrose-induced oxidative stress but not ER stress, while GPX1 knockout enhanced oxidative stress but had no effect on ER stress. These results suggest that ebselen targets only oxidative stress but not ER stress. Copyright © 2015. Published by Elsevier Inc.

Differential Effects of Leptin and Adiponectin in Endothelial Angiogenesis

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Raghu Adya

2015-01-01

Full Text Available Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD. In relation to this, adipose tissue secreted factors termed “adipokines” have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor and cardiovascular system (endothelial dysfunction leading to atherosclerosis. Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity.

Cultivation of corneal endothelial cells on a pericellular matrix prepared from human decidua-derived mesenchymal cells.

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Ryohei Numata

Full Text Available The barrier and pump functions of the corneal endothelium are essential for the maintenance of corneal transparency. Although corneal transplantation is the only current therapy for treating corneal endothelial dysfunction, the potential of tissue-engineering techniques to provide highly efficient and less invasive therapy in comparison to corneal transplantation has been highly anticipated. However, culturing human corneal endothelial cells (HCECs is technically difficult, and there is no established culture protocol. The aim of this study was to investigate the feasibility of using a pericellular matrix prepared from human decidua-derived mesenchymal cells (PCM-DM as an animal-free substrate for HCEC culture for future clinical applications. PCM-DM enhanced the adhesion of monkey CECs (MCECs via integrin, promoted cell proliferation, and suppressed apoptosis. The HCECs cultured on the PCM-DM showed a hexagonal morphology and a staining profile characteristic of Na⁺/K⁺-ATPase and ZO-1 at the plasma membrane in vivo, whereas the control HCECs showed a fibroblastic phenotype. The cell density of the cultured HCECs on the PCM-DM was significantly higher than that of the control cells. These results indicate that PCM-DM provides a feasible xeno-free matrix substrate and that it offers a viable in vitro expansion protocol for HCECs while maintaining cellular functions for use as a subsequent clinical intervention for tissue-engineered based therapy of corneal endothelial dysfunction.

Measurements of intraocular pressure by Goldmann tonometry, Tonopen XL, and the transpalpebral tonometer, TGDc-01, after penetrating keratoplasty: a comparativye study.

Science.gov (United States)

Shemesh, Gabi; Waisbourd, Michael; Varssano, David; Michaeli, Adi; Lazar, Moshe; Kurtz, Shimon

2009-08-01

The aim of this study was to compare intraocular pressure (IOP) measurements obtained by Goldmann tonometry (GT), the Tonopen XL, and a new transpalpebral tonometer, TGDc-01, in eyes that had undergone penetrating keratoplasty (PKP). IOP was measured in post-PKP eyes by means of GT, Tonopen XL, and TGDc-01. Central corneal thickness measurements were also obtained for all eyes. Forty-five eyes of 43 patients were enrolled in the study. The mean IOP difference (+/-SD) was -0.42 +/- 5.83 mm Hg between GT and Tonopen and 3.20 +/- 7.55 mm Hg between GT and TGDc-01. The correlation coefficient was 0.84 between GT and Tonopen XL (P tonometer is simply inaccurate or whether avoiding contact with the corneal graft by measuring IOP through the eyelid enables it to provide more accurate IOP readings than those obtained by transcorneal techniques.

VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression.

Science.gov (United States)

Morini, Marco F; Giampietro, Costanza; Corada, Monica; Pisati, Federica; Lavarone, Elisa; Cunha, Sara I; Conze, Lei L; O'Reilly, Nicola; Joshi, Dhira; Kjaer, Svend; George, Roger; Nye, Emma; Ma, Anqi; Jin, Jian; Mitter, Richard; Lupia, Michela; Cavallaro, Ugo; Pasini, Diego; Calado, Dinis P; Dejana, Elisabetta; Taddei, Andrea

2018-01-19

The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability. We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. We compared a VEC-null cell line with the same line reconstituted with VEC wild-type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5 , vascular endothelial-protein tyrosine phosphatase ( VE-PTP ), and von Willebrand factor ( vWf ). Mechanistically, VEC exerts this effect by inhibiting polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 (Forkhead box protein O1) and β-catenin, which contribute to PRC2 (polycomb repressive complex-2) binding to promoter regions of claudin-5 , VE-PTP , and vWf . VEC/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2 [enhancer of zeste homolog 2]) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VEC association increases Ezh2 recruitment to claudin-5 , VE-PTP , and vWf promoters, causing gene downregulation. RNA sequencing comparison of VEC-null and VEC-positive cells suggested a more general role of VEC in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased levels of claudin-5 and VE-PTP. These

Dynamics of circulating endothelial cells and endothelial progenitor cells in breast cancer patients receiving cytotoxic chemotherapy

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Kuo Yu-Hsuan

2012-12-01

Full Text Available Abstract Background The abundance of circulating endothelial cells (CECs and circulating endothelial progenitor cells (CEPs, which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy. Methods We collected blood samples from 15 breast cancer patients, who received a total of 56 courses of systemic chemotherapy, and measured the CECs, viable CECs (V-CECs, and CEPs by six-color flow cytometry within the seven days prior to chemotherapy, twice a week during the first and second cycles of chemotherapy, and then once a week during the subsequent cycles. Results The CEC, V-CEC, and CEP levels all significantly decreased from day 1 of treatment to the first week of chemotherapy. After one week of chemotherapy, the CEC and V-CEC levels returned to a level similar to day 1. The CEP level remained significantly reduced after the first week of chemotherapy, but gradually rebounded until the next course of chemotherapy. After six cycles of chemotherapy, the total number of CEC and V-CEC cells trended toward a decrease and the CEP cells toward an increase. Clinical factors, including the existence of a tumor, chemotherapy regimens, and the use of granulocyte colony stimulating factor, did not significantly affect these results. Conclusions The CEC and CEP counts change dynamically during each course of chemotherapy and after the chemotherapy cycles, providing background data for any future study planning to use CECs and CEPs as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.

Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

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Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

2018-01-01

Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P age-related macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

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Maskomani Silambarasan

2016-04-01

Full Text Available Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose and at various time intervals (6, 12, 24 and 48 h. miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

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Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

2017-09-15

Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

DEFF Research Database (Denmark)

Wang, X; Häring, M-F; Rathjen, Thomas

2017-01-01

in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

Functional and gene expression analysis of hTERT overexpressed endothelial cells

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Haruna Takano

2008-09-01

Full Text Available Haruna Takano1, Satoshi Murasawa1,2, Takayuki Asahara1,2,31Institute of Biomedical Research and Innovation, Kobe, Japan; 2RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; 3Tokai University of School of Medicine, Tokai, JapanAbstract: Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT overexpressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.Keywords: endothelial, telomerase, senescence, oxidative stress, anti-apoptosis, PI3K/Akt pathway

Dynamical Systems Approach to Endothelial Heterogeneity

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Regan, Erzsébet Ravasz; Aird, William C.

2012-01-01

Rationale Objective Here we reexamine our current understanding of the molecular basis of endothelial heterogeneity. We introduce multistability as a new explanatory framework in vascular biology. Methods We draw on the field of non-linear dynamics to propose a dynamical systems framework for modeling multistability and its derivative properties, including robustness, memory, and plasticity. Conclusions Our perspective allows for both a conceptual and quantitative description of system-level features of endothelial regulation. PMID:22723222

Successful treatment of refractory TAFRO syndrome with elevated vascular endothelial growth factor using thyroxine supplements.

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Oka, Satoko; Ono, Kazuo; Nohgawa, Masaharu

2018-04-01

Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism.

Weight loss improves biomarkers endothelial function and systemic ...

African Journals Online (AJOL)

Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function ...

Laser welding in penetrating keratoplasty and cataract surgery of pediatric patients: early results

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Rossi, Francesca; Pini, Roberto; Menabuoni, Luca; Malandrini, Alex; Canovetti, Annalisa; Lenzetti, Ivo; Capozzi, Paolo; Valente, Paola; Buzzonetti, Luca

2013-03-01

Diode laser welding of ocular tissues is a procedure that enables minimally invasive closure of a corneal wound. This procedure is based on a photothermal effect: a water solution of Indocyanine Green (ICG) is inserted in the surgical wound, in order to stain the corneal tissue walls. The stained tissue is then irradiated with a low power infrared diode laser, delivering laser light through a 300-μm core diameter optical fiber. This procedure enables an immediate closure of the wounds: it is thus possible to reduce or to substitute the use of surgical threads. This is of particular interest in children, because the immediate closure improves refractive outcome and anti-amblyopic effect; moreover this procedure avoids several general anaesthesia for suture management. In this work, we present the first use of diode laser welding procedure in paediatric patients. 5 selected patients underwent cataract surgery (Group 1), while 4 underwent fs-laserassisted penetrating keratoplasty (Group 2). In Group 1 the conventional surgery procedure was performed, while no stitches were used for the closure of the surgical wounds: these were laser welded and immediately closed. In Group 2 the donor button was sutured upon the recipient by 8 single stitches, instead of 16 single stitches or a running suture. The laser welding procedure was performed in order to join the donor tissue to the recipient bed. Objective observations in the follow up study evidenced a perfect adhesion of the laser welded tissues, no collateral effects and an optimal restoration of the treated tissues.

Vascular endothelial growth factor and basic fibroblast growth factor expression positively correlates with angiogenesis and peritumoural brain oedema in astrocytoma

International Nuclear Information System (INIS)

Jang, F.F.; Wei, W.

2008-01-01

Astrocytoma is the most malignant intracranial neoplasm and is characterized by high neovascularization and peritumoural brain oedema. Angiogenesis is a complicated process in oncogenesis regulated by the balance between angiogenic and antiangiogenic factors. The expression of two angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor were investigated using immunohistochemistry for astrocytoma from 82 patients and 11 normal human tissues. The expression of vascular endothelial growth factor and basic fibroblast growth factor positively correlate with the pathological grade of astrocytoma, microvessel density numbers and brain oedema, which may be responsible for the increased tumour neovascularization and peritumoural brain oedema. The results support the idea that inhibiting vascular endothelial growth factor and basic fibroblast growth factor are useful for the treatment of human astrocytoma and to improve patient's clinical outcomes and prognosis. (author)

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

LENUS (Irish Health Repository)

Harmon, D

2012-02-03

BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b\\/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+\\/-46% vs. 91+\\/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+\\/-46% vs. 129+\\/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+\\/-3.7 vs. 43+\\/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+\\/-0.4 vs. 2.6+\\/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+\\/-3.3 vs. 116+\\/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+\\/-0.3 vs. 2.6+\\/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM

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Freiberg, Florentina J; Brynskov, Troels; Munk, Marion R

2017-01-01

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016...... at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were...... performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS: A total of 134,701 intravitreal injections were performed at the 3 sites between...

Weighing of risk factors for penetrating keratoplasty graft failure: application of Risk Score System

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Abdo Karim Tourkmani

2017-03-01

Full Text Available AIM: To analyze the relationship between the score obtained in the Risk Score System (RSS proposed by Hicks et al with penetrating keratoplasty (PKP graft failure at 1y postoperatively and among each factor in the RSS with the risk of PKP graft failure using univariate and multivariate analysis. METHODS: The retrospective cohort study had 152 PKPs from 152 patients. Eighteen cases were excluded from our study due to primary failure (10 cases, incomplete medical notes (5 cases and follow-up less than 1y (3 cases. We included 134 PKPs from 134 patients stratified by preoperative risk score. Spearman coefficient was calculated for the relationship between the score obtained and risk of failure at 1y. Univariate and multivariate analysis were calculated for the impact of every single risk factor included in the RSS over graft failure at 1y. RESULTS: Spearman coefficient showed statistically significant correlation between the score in the RSS and graft failure (P0.05 between diagnosis and lens status with graft failure. The relationship between the other risk factors studied and graft failure was significant (P<0.05, although the results for previous grafts and graft failure was unreliable. None of our patients had previous blood transfusion, thus, it had no impact. CONCLUSION: After the application of multivariate analysis techniques, some risk factors do not show the expected impact over graft failure at 1y.

The targeting expression of the vascular endothelial growth factor gene in endothelial cells regulated by HRE.ppET-1.

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Zheng, Xiangrong; Zhang, Shangshang; Yang, Yujia; Wang, Xia; Zhong, Le; Yu, Xiaohe

2008-11-01

The success of gene therapy depends largely on the efficacy of gene delivery vector systems that can deliver genes to target organs or cells selectively and efficiently with minimal toxicity. Here, we show that by using the HRE.ppET-1 regulatory element, we were able to restrict expression of the transgene of vascular endothelial growth factor (VEGF) to endothelial cells exclusively in hypoxic conditions. Eukaryotic expression vectors such as pEGFP-HRE.ppET-1, pcDNA3.1-VEGF+Pa, pcDNA3.1-ppET-1+ EGF+Pa, and pcDNA3.1-HRE.ppET-1+VEGF+Pa were constructed by using a series of nuclear molecule handling methods like PCR, enzyme digestion. The recombinant vectors were transfected into HUVEC cells and HL7702 cells by the lipofectin method. GFP expression was observed with a fluorescence microscope to validate the specificity of expression in endothelial cells under the regulation of HRE.ppET-1 element. Cobalt chloride (final concentration 100 mumol/L) was added to the medium to mimic hypoxia in vitro. After transfection of vectors, the expression of VEGF mRNA was detected by RT-PCR, and the expression of VEGF was detected by Western blotting and ELISA methods under normoxia and hypoxia, respectively. The cell proliferation rate was detected by the MTT test. The expression of GFP revealed that the exterior gene was transcripted effectively in endothelial cells regulated by the HRE.ppET-1 element, while the expression of GFP was very weak in nonendothelial cells. The results of RT-PCR, Western blotting and ELISA showed that VEGF gene expression in the pcDNA3.1-HRE.ppET-1+VEGF+Pa group and in the pcDNA3.1-ppET-1+VEGF+Pa group was higher in hypoxia than it was in normoxia (PHRE.ppET-1 element was expressed specifically in endothelial cells, and can increase the expression of VEGF in hypoxia and stimulate proliferation of endothelial cells. Taking advantage of these facts could greatly improve the efficiency of gene therapy. The vector would be valuable for various gene transfer

Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation

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Vallon, Mario, E-mail: m.vallon@arcor.de [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Rohde, Franziska; Janssen, Klaus-Peter [Chirurgische Klinik und Poliklinik, Technische Universitaet Muenchen, Munich (Germany); Essler, Markus [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany)

2010-02-01

Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis. So far, the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified. Here, we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel, during capillary morphogenesis in a three-dimensional collagen I matrix, and upon confluence on a two-dimensional matrix. TEM5 expression was not induced by a variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation. Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells.

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

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Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

The Expression Profiles of Lysophospholipid Receptors (LPLRs in Different Endothelial Cells

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Yu-Wei Lee

2006-03-01

Full Text Available Sphingosine-1-phosphate (S1P and lysophosphatidic acid (LPA are two bioactive lysophospholipids (LPLs, stored primarily in platelets and released during platelet activation. Both LPLs are capable of regulating endothelial cell functions. The physiological functions of S1P and LPA are mediated by interacting with eight different G-protein coupled receptors: S1P1 through 5 and LPA1 through 3, which activate three different heterotrimeric GTP proteins－including Gi、Gq and G(12/13. The expression of LPL receptors in endothelial cells would affect the responses of S1P and LPA to these cells. There is no previous report discussing the expression profiles of LPL receptors in different endothelial cells from various species. In this study, we aim to investigate the expression profiles of S1P and LPA receptors in different endothelial cells isolated from human, rat, mouse and bovine origin. We used RT-PCR to determine LPLs receptors expression profiles in different endothelial cells. Our results indicated that endothelial cells from various species express different LPL receptors. Endothelial cells isolated from the same source of different species also had different LPLs receptors expression profiles. Therefore, different endothelial cells should respond to LPLs in different manners.

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.

LENUS (Irish Health Repository)

Moloney, Michael A

2010-10-01

Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin. In young asymptomatic smokers, taurine supplementation has a beneficial impact on macrovascular function, assessed by FMD, and shows an up-regulation of nitric oxide from monocyte-endothelial cell interactions. We hypothesise that taurine supplementation reverses early endothelial abnormalities in young male type 1 diabetics, as assessed by applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry. Asymptomatic, male diabetics (n=9) were scanned prior to treatment and then randomised in a double-blind cross-over fashion to receive either 2 weeks placebo or taurine. Control patients (n=10) underwent a baseline scan. Assessed diabetics had detectable, statistically significant abnormalities when compared with controls, in both arterial stiffness (augmentation index) and brachial artery reactivity (FMD). Both of these parameters were returned to control levels with 2 weeks taurine supplementation. In conclusion, 2 weeks taurine supplementation reverses early, detectable conduit vessel abnormalities in young male diabetics. This may have important implications in the long-term treatment of diabetic patients and their subsequent progression towards atherosclerotic disease.

Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

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Dincer UD

2014-12-01

Full Text Available U Deniz Dincer Department of Basic and Clinical Pharmacology, School of Medicine, Bezmialem Vakif University (BAVU, Fatih/Istanbul, Turkey Abstract: Gestational diabetes mellitus (GDM has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs. Understanding the vessel-forming ability of human umbilical cord blood (HUCB-derived endothelial colony-forming cells (ECFCs against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS, platelet (PECAM-1 endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule, vascular endothelial growth factor A, (VEGFA and insulin-like growth factor 1 (IGF1. Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs' proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. Keywords: endothelial progenitor cells, gestational diabetes mellitus, chronic hypoxia, human cord blood