Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty.

PurposeMatrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis.MethodsProtein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas.ResultsLuminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients.ConclusionsMultiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization

Can the application of computed tomography laser mammography (CTLM) in dense breast (category 3,4 according to ACR) examinations combined with x-ray mammography enhance the detection of breast cancer?

Background: The aim of this study was an attempt to answer the question whether laser mammography in dense breast (classified as category 3,4 according to ACR) examination together with x-ray mammography can enhance the detection of breast cancer. Material/Method: 248 women who had undergone a CTLM examination and mammography in the Department of Radiology of Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in the years 2005-2007 were analyzed retrospectively. In these examinations, x-ray mammography did not reveal lesions (BIRADS 1, category 3 and 4 according to ACR). An interval between CTLM and mammography did not exceed 30 days. The examination result was verified by cytology/histopathology or observation after a minimum of 12 months provided a regular result. CTLM visualizes normal and pathological blood vessels and tissues which are rich in blood, because laser rays used in CTLM (808nm) are more absorbable by hemoglobin than by the surrounding tissue, making it possible to show a malignant tumor by its accompanying angiogenesis. The result of CTLM mammography was qualified either as the presence (+) or absence (–) of angiogenesis. Results: Among 248 women, angiogenesis was discovered by CTLM in 48 cases, in the CTLM (+) Group 13/48 women were diagnosed with breast cancer, whereas 35/48 were diagnosed with benign lesions. Angiogenesis was not identified in 200 women, in the CTLM (-) group 13/200 were diagnosed finally with cancer, with 187/200 patients having no malignancy. Ultimately, in the group of 248 women (with dense breast, category 3 and 4 according to ACR), in whom x-ray mammography did not reveal malignant processes (BIRADS 1), 26 cancers were detected out of which 13 were revealed with CTLM Conclusions: Computed Tomography Laser Mammography, when used as an adjunct to x-ray mammography, enhances the detection of breast cancer in women with dense breast tissue

Arterial pathology in canine mucopolysaccharidosis-I and response to therapy.

Mucopolysaccharidosis-I (MPS-I) is an inherited deficiency of α-L-iduronidase (IdU) that causes lysosomal accumulation of glycosaminoglycans (GAG) in a variety of parenchymal cell types and connective tissues. The fundamental link between genetic mutation and tissue GAG accumulation is clear, but relatively little attention has been given to the morphology or pathogenesis of associated lesions, particularly those affecting the vascular system. The terminal parietal branches of the abdominal aorta were examined from a colony of dogs homozygous (MPS-I affected) or heterozygous (unaffected carrier) for an IdU mutation that eliminated all enzyme activity, and in affected animals treated with human recombinant IdU. High-resolution computed tomography showed that vascular wall thickenings occurred in affected animals near branch points, and associated with low endothelial shear stress. Histologically these asymmetric 'plaques' entailed extensive intimal thickening with disruption of the internal elastic lamina, occluding more than 50% of the vascular lumen in some cases. Immunohistochemistry was used to show that areas of sclerosis contained foamy (GAG laden) macrophages, fibroblasts and smooth muscle cells, with loss of overlying endothelial basement membrane and claudin-5 expression. Lesions contained scattered cells expressing nuclear factor-κβ (p65), increased fibronectin and transforming growth factor β-1 signaling (with nuclear Smad3 accumulation) in comparison to unaffected vessels. Intimal lesion development and morphology was improved by intravenous recombinant enzyme treatment, particularly with immune tolerance to this exogenous protein. The progressive sclerotic vasculopathy of MPS-I shares some morphological and molecular similarities to atherosclerosis, including formation in areas of low shear stress near branch points, and can be reduced or inhibited by intravenous administration of recombinant IdU

Traitement des membranes néovasculaires myopiques par ranibizumab : résultats à long terme.

Background: To report our functional results of efficacy of intravitreal ranibizumab (IVR) for submacular choroidal neovessels (CNV) in high myopia, and to compare the role of optical coherence tomography (OCT), fluorescein angiography (FA) and visual acuity changes in the treatment decision prior to each injection. Patients and methods: This is a retrospective study performed in Jules Gonin Eye Hospital. It included all patients with myopic CNV treated with IVR injections with a minimal follow-up of 24 months. After an induction dosing from 1 to 3 injections, the follow-up was based on a PRN regimen. Ophthalmic evaluation, best corrected visual acuity (BCVA), and OCT were done at each visit, and FA at baseline and if neovascular activity was suspected. Retreatment criteria included metamorphopsia, visual loss of ≥5 ETDRS letters, any fluid on OCT and/or leakage on FA. Results: 24 eyes were included in the study. Mean follow-up was 49 months. Mean BCVA improved significantly from 62.8 ±13.8 letters at baseline to 72.8 ±12.9 letters at last follow-up visit (p=0.001). The mean number of injections was 2.2 in the first year and below 1 for the following years. The sensitivity of FA, SD OCT, and BCVA loss ≥ 5 letters were 62.6%, 51.4%, and 40% respectively. The FA showed significant higher sensitivity in treatment decision than OCT (p=0.007). Conclusion: Our study showed that IVR provides a significant long term visual benefit in myopic CNV with a small number of injections. FA has a preponderant role in the treatment decision of active myopic CNV. PRECIS Our study showed long term efficacy of ranibizumab in the treatment of myopic CNV. We studied also the contribution of different modalities (OCT, FA and BCVA loss) in the retreatment decision

Long-term follow-up of myopic choroidal neovascularization treated with ranibizumab

PURPOSE: To evaluate the long-term safety and efficacy of intravitreal ranibizumab in the treatment of myopic choroidal neovascularization (CNV). METHODS: Three-year retrospective, nonrandomized, interventional case series. Forty eyes of 39 patients with myopic CNV were included; 15 with previous photodynamic therapy, and 25 naïve eyes. Best-corrected visual acuity (BCVA) changes, central foveal thickness (CFT), and number of treatments were assessed, from baseline to month 36. RESULTS: Mean visual acuity improved from 55.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 59.7 letters at 12 months (p = 0.07), 61.8 letters at 24 months (p = 0.008) and 63.4 letters at 36 months (p = 0.039). Twenty-five percent of the patients gained ≥15 letters (3 lines) at 12 months, 30% at 24 months and 35% at 36 months. There was a mean reduction of 80 μm in CFT (p < 0.001). A mean of 4.1 injections were performed in the first year, 2.4 in the second year and 1.1 in the third year. Fifty-three percent of the eyes had no need for treatment during the third year of follow-up. CONCLUSIONS: Intravitreal ranibizumab seems to be an effective and safe therapeutic procedure to treat CNV in highly myopic eyes, with a high proportion of patients gaining or stabilizing BCVA at a 3-year follow-up.info:eu-repo/semantics/publishedVersio

Sirtuin1 Over-Expression Does Not Impact Retinal Vascular and Neuronal Degeneration in a Mouse Model of Oxygen-Induced Retinopathy

Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy

The Diagnostic Accuracy of Abdominal Ultrasound Imaging for Detection of Ovarian Masses

Background/Objective: Detection of the tissue diagnosis of ovarian space occupying lesions (OSOL) has remained a challenging task for sonographers since many adnexal masses have nonspecific sonographic appearances. Our objective was to evaluate the accuracy of the abdominal sonographic diagnosis of adnexal masses in 79 women with a known OSOL undergoing laparotomy for ovarian masses in Tabriz Alzahra's Haspital, northwestern Iran. Patients and Methods: From March 2004 to February 2005, sonographic reports of each patient were compared with postoperative findings. Results: Comparison of the preoperative sonographic and final pathologic diagnoses revealed a correct sonographic diagnosis in 77% of patients. The identification of ovarian cystic teratoma was correct in 17/24 cases (sensitivity of 71% and specificity of 98%). The identification of ovarian malignancy was correct in 7/10 patients (sensitivity of 70% and specificity of 98.5%). Sonograms were frankly misread in 14/79 cases, and were missed in 4/79 cases. Conclusion: In conclusion, our results show high resolution abdominal ultrasonography is an effective method in diagnosis of ovarian tumors and on 70% of patients can differentiate malignant tumors from benign tumors

Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. METHODS: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for > or = 12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. RESULTS: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P or = 3 lines, 44% improved > or = 2 lines, 65% improved > or = 1 line, and 79% improved > or = 0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. CONCLUSION: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety