NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.

Microbiological and clinical effects of enamel matrix derivative and sustained-release micro-spherical minocycline application as an adjunct to non-surgical therapy in peri-implant mucosal inflammation

OBJECTIVES: The purpose of this study was to compare the microbial and clinical effects of mechanical debridement (MD) alone or in combination with the application of enamel matrix derivative (EMD) and sustained-release micro-spherical minocycline (MSM) for treatment of peri-implant mucosal infl ammation (PIMI). MATERIALS AND METHODS: Subjects with at least one implant with PIMI were included and divided into control and two different test groups. In all three groups, MD was performed. In the MSM group, following MD, MSM was placed subgingivally around the implants. In the EMD group, after MD, EMD was placed in the sulcus around the implants. Sampling of peri-implant crevicular fl uid for microbial analysis with real-time polymerase chain reaction and recording of probing depth (PD) and bleeding on probing (BOP) were performed prior to as well as two weeks and three months after treatment. Median values and interquartile range were estimated for each variable during the various assessment intervals of the study. RESULTS: In all groups, at two weeks and three months, the counts of Porphyromonas gingivalis decreased significantly compared to baseline. Levels of P. gingivalis were significantly reduced in MSM (P<0.001) and EMD (P=0.026) groups compared to the control group. Also, clinical parameters improved significantly at two weeks and three months. Reduction of PD was significant in MSM (P<0.001) and EMD (P<0.001) groups. The decrease in BOP in the MSM, EMD, and control groups was 60%, 50%, and 20%, respectively. CONCLUSION: The use of MSM and EMD can be an adjunctive treatment for management of PIMI and improves clinical parameters and reduces P. gingivalis burden three months after treatment.

Mild toxic anterior segment syndrome mimicking delayed onset toxic anterior segment syndrome after cataract surgery.

Toxic anterior segment syndrome (TASS) is an acute sterile postoperative anterior segment infl ammation that may occur after anterior segment surgery. I report herein a case that developed mild TASS in one eye after bilateral uneventful cataract surgery, which was masked during early postoperative period under steroid eye drop and mimicking delayed onset TASS after switching to weaker steroid eye drop.

Topical nepafenac 0.1% alone versus prednisolone acetate 1% as postoperative anti-inflammatory agents in small gauge vitrectomy.

Aim: To compare the effi cacy of postoperative topical nepafenac (0.1%) with prednisolone acetate (1%) as anti-infl ammatory agents in eyes undergoing Transscleral Sutureless Vitrectomy (TSV). Se􀄴 ings and Design: Prospective, double-blind, randomized, single center clinical study. Materials and Methods: Eighty eyes of 76 subjects, who underwent small gauge vitrectomy, were included in the study. The subjects who fulfi lled the inclusion criteria were randomized to either topical nepafenac only (Group 1) or prednisolone acetate only (Group 2), to be used as postoperative anti-infl ammatory agents. The subjects were reviewed on days 1, 30, and 90. Ocular and adnexal infl ammation was appropriately graded using the standardized classifi cation. Grading of ocular pain was done on the Visual Analog Scale (VAS). Statistical Analysis: The Wilcoxon rank-sum test, using two-sided analysis, was used. Results: During the follow-up, both Group 1 and Group 2 did not have a signifi cant diff erence related to the grade of the anterior chamber infl ammation (P > 0.05) or adnexal infl ammation (P > 0.05). Pain perception was less in the subjects in Group 1 as compared to subjects in Group 2, but was not statistically signifi cant (P > 0.05). Conclusion: Postoperative topical nepafenac was non-inferior to prednisolone acetate in reducing postoperative ocular infl ammation in eyes undergoing TSV.

Cytokines and Biologics in non-infectious autoimmune uveitis: Bench to Bedside.

Intraocular infl ammatory eye disease is one of the important causes of ocular morbidity. Even though the prevalence of uveitis is less common in relation to diabetic retinopathy, glaucoma or age related macular degeneration, the complexity and heterogeneity of the disease makes it more unique. Putative uveitogenic retinal antigens incite innate immunity by the process of antigen mimicry and have been shown to be associated in patients with intraocular infl ammatory disease by numerous experimental studies. Laboratory diagnostic tools to aid the etiologic association in intraocular infl ammatory disease have evolved over the last two decades and we are entering into an era of molecular diagnostic tests. Sophisticated novel technologies such as multiplex bead assays to assess biological signatures have revolutionized the management of complex refractory uveitis. Nevertheless, there is still a long way to go to establish the causal relationship between these biomarkers and specifi c uveitic entities. Experimental studies have shown the supreme role of infl iximab in the management of Behcet’s disease. Despite signifi cant experimental and case control studies, the defi ciency of randomized clinical trials using these biologic agents has handicapped us in exploring them as a front line therapy in severe refractory uveitis. Studies still need to answer the safety of these potentially life threatening drugs in a selected group of patients and determine when to commence and for how long the treatment has to be given. This review article covers some basic concepts of cytokines in uveitis and their potential application for therapy in refractory uveitis.