Matrix Metalloproteinase 9-induced inc. in intestinal epith. tight junct. permeability contributes to severity of DSS colitis
Matrix Metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.
Abstract
Recent studies have implicated a pathogenic role for Matrix Metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Though loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild type (WT) and MMP-9-/- mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescent labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9-/- mice. The colonic protein expression of myosin light chain kinase (MLCK), and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9-/- mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK-/- mice and MLCK inhibitor ML-7 treated WT mice. DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9-/- mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. This data suggest role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.
Copyright © 2015, American Journal of Physiology- Gastrointestinal and Liver Physiology.
KEYWORDS:
Matrix metalloproteinase; myosin light chain kinase; tight junction
- PMID:
- 26514773
- [PubMed - as supplied by publisher]
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1. | J Cataract Refract Surg. 2015 Aug;41(8):1699-704. doi: 10.1016/j.jcrs.2014.12.056.
Effect of a hyaluronic acid and carboxymethylcellulose ophthalmic solution on ocular comfort and tear-film instability after cataract surgery.Mencucci R1, Boccalini C2, Caputo R2, Favuzza E2.
Author information:
AbstractPURPOSE:To evaluate the efficacy and safety of using sodium hyaluronate 0.1% and carboxymethylcellulose 0.5% artificial tears for ocular discomfort and tear-film stability in eyes after cataract surgery. SETTING:Twenty ophthalmic centers in Italy. DESIGN:Prospective randomized case series. METHODS:This study enrolled patients scheduled for unilateral cataract surgery. After surgery, patients received artificial tears and a topical steroid-antibiotic (study group) or topical steroid-antibiotic alone (control group) and were assessed postoperatively at 1 and 5 weeks. Outcome measures were tear breakup time (TBUT), ocular surface disease index (OSDI), frequency of dry-eye symptoms evaluated using a visual analog scale (VAS), and corneal fluorescein staining. RESULTS:The study comprised 282 patients. At 5 weeks, the mean TBUT was statistically significantly higher in the study group than in the control group (P = .0003). The mean OSDI score statistically significantly improved in both groups from 1 to 5 weeks (P < .0001 for both groups); however, there was no statistically significant difference between the groups at these timepoints. The artificial tears statistically significantly improved VAS-assessed dry-eye symptoms in the study group compared with the control group at 5 weeks (P < .001). The mean corneal fluorescein staining was significantly reduced in the study group compared with the control group at 5 weeks (P = .002 versus P = .05, respectively). No treatment-related adverse events were reported. CONCLUSION:Sodium hyaluronate 0.1% and carboxymethylcellulose 0.5% ophthalmic solution was effective and well tolerated in reducing dry-eye disease symptoms and improving the clinical outcome after cataract surgery. FINANCIAL DISCLOSURE:No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved. |
PMID: 26432128 [PubMed - in process] | |
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2. | Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47.
Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?Saad L1, Washington I2.
Author information:
AbstractWe discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway. |
PMID: 26427432 [PubMed - in process] | |
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3. | Adv Exp Med Biol. 2016;854:111-8. doi: 10.1007/978-3-319-17121-0_16.
Nanoceria: a Potential Therapeutic for Dry AMD.Cai X1, McGinnis JF2,3.
Author information:
AbstractAge-related macular degeneration (AMD) is the leading cause of blinding diseases. The "dry" form of AMD is the most common form of AMD. In contrast to the treatable neovascular (wet) AMD, no effective treatment is available for dry AMD. In this review, we summarize the animal models and therapeutic strategies for dry AMD. The novel candidates as potential treatment targets and the potential effectiveness of nanoceria as a treatment of dry AMD are also discussed. |
PMID: 26427401 [PubMed - in process] | |
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4. | Adv Exp Med Biol. 2016;854:103-9. doi: 10.1007/978-3-319-17121-0_15.
Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.Author information:
AbstractDry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. |
PMID: 26427400 [PubMed - in process] | |
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5. | Breast. 2015 Sep 25. pii: S0960-9776(15)00185-X. doi: 10.1016/j.breast.2015.08.008. [Epub ahead of print]
Dry eyes and AIs: If you don't ask you won't find out.Inglis H1, Boyle FM2, Friedlander ML3, Watson SL4.
Author information:
AbstractOBJECTIVES:Our objective was to investigate the hypothesis that women on adjuvant aromatase inhibitors (AIs) for treatment of breast cancer have a higher prevalence of dry eye syndrome (DES) compared with controls. MATERIALS AND METHODS:Exposure and control groups were recruited. A cross sectional questionnaire-based study was performed. Demographic data and medical histories were collected. The presence of dry eye syndrome was determined by the ocular surface disease index (OSDI). The Functional Assessment of Cancer Treatment - Endocrine Subscale (FACT-ES) was performed to investigate correlations with other side effects of AIs. RESULTS:93 exposure group and 100 control group questionnaires were included. The groups were similar in all demographic variables. The prevalence of dry eye syndrome was 35% (exposure) and 18% (control) (p < 0.01, OR 2.5). AIs were the only factor associated with dry eyes. The OSDI score was negatively correlated with the total FACT-ES score and positively correlated with duration of treatment. CONCLUSION:Our study is the first to use a validated questionnaire to assess for DES in this population. DES is significantly more prevalent in women on AIs compared with controls. This is a newly emerging, and easily treated side effect of AIs. Self-reporting of dry eye symptoms underestimates the prevalence of DES with AIs. We recommend routine screening of patients on AIs with the OSDI with the aim of improving patient quality of life and possibly adherence. Copyright © 2015 Elsevier Ltd. All rights reserved. |
PMID: 26422124 [PubMed - as supplied by publisher] | |
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6. | Cornea. 2015 Sep 28. [Epub ahead of print]
Dry Eye Signs and Symptoms Persist During Systemic Neutralization of IL-1β by Canakinumab or IL-17A by Secukinumab.Author information:
AbstractPURPOSE:To evaluate whether inhibition of the proinflammatory cytokines IL-1β or IL-17A by canakinumab or secukinumab, respectively, influence the signs and symptoms of dry eye. METHODS:In a randomized, double-masked, placebo-controlled, outpatient clinical trial, 72 patients with moderate to severe dry eye were randomly assigned in a 1:1:1 ratio to treatment with a single intravenous dose of canakinumab, of secukinumab, or of placebo. Signs and symptoms of dry eye were evaluated on the treatment day and 1 week, 4 weeks, and 8 weeks after treatment. The prespecified primary efficacy endpoint was corneal staining in the study eye 4 weeks after treatment. Secondary endpoints included tear production (Schirmer test), tear film breakup time, conjunctival redness, the ocular surface disease index (OSDI), the frequency of a desire for a topical ocular lubricant, and visual acuity. RESULTS:Of the 71 patients included in the analysis of safety, the rate of adverse events was similar between treatment groups. The course of corneal staining scores from baseline to 4 weeks, respectively, were for canakinumab 1.46 to 1.33 (P = 0.62 compared with placebo), for secukinumab 1.46 to 1.23 (P = 0.22), and for placebo 1.68 to 1.42. There were no changes in the other measures of efficacy beyond what was within the range expected for stochastic day-to-day variation. CONCLUSIONS:The results suggest that the inhibition of IL-1β or IL-17A obtained by systemic administration of neutralizing drugs does not influence the severity of dry eye.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially. |
PMID: 26418434 [PubMed - as supplied by publisher] | |
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7. | Tissue Eng Part A. 2015 Sep 28. [Epub ahead of print]
Three-dimensional culture of functional adult rabbit lacrimal gland epithelial cells on decellularized scaffold.Lin H1, Sun G2, He H3, Botsford B4, Li M5, Elisseeff JH6,7, Yiu SC8.
Author information:
AbstractAqueous tear-deficient dry eye disease is a multifactorial chronic disorder in which the lacrimal gland fails to produce enough tears to maintain a healthy ocular surface. Some severe cases may develop corneal damage and significant vision loss. Treatment primarily involves palliation using ocular surface lubricants, but can only provide temporary relief. Construction of a bioengineered lacrimal gland having functional secretory epithelial cells is a potentially promising option for providing long-term relief to severe dry eye patients. Using sphere-forming culture techniques, we cultured adult rabbit lacrimal gland progenitor cells and prepared a lacrimal gland scaffold by decellularization. When progenitor cells were seeded onto the decellularized scaffold, they formed duct- and acinar-like structures in the three dimensional culture system. Lacrimal gland epithelial cells showed good cell viability, cell differentiation and secretory function in decellularized lacrimal gland matrix, as indicated by morphology, immunostaining and beta-hexosaminidase secretion assay. This study demonstrated the potential suitability of utilizing tissue-specific progenitor cells and a tissue-derived bioscaffold for lacrimal gland restoration. |
PMID: 26414959 [PubMed - as supplied by publisher] | |
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8. | Eye Sci. 2015 Mar;30(1):48-52.
Research Progress on Ocular Surface Changes after Fem- tosecond Laser Small Incision Lenticule Extraction.AbstractThe femtosecond laser has a number of advantages, such as short pulse time, high instantaneous power, high repetition rate, low monopulse energy, and small thermal effect. Femtosecond laser-assisted small incision lenticule extraction (SMILE) is becoming the new direction in refractive surgery, and the ocular surface changes after SMILE are attracting increasingly more attention. This article reviews adverse effects, including dry eye, injury of corneal nerves, and ocular surface inflammation, occurring after SMILE. |
PMID: 26390799 [PubMed - indexed for MEDLINE] | |
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9. | Medsurg Nurs. 2015 Mar-Apr;24(2):89-93.
Computer Vision Syndrome: A Review of Literature.AbstractComputer vision syndrome is caused by prolonged computer use. Symptoms, treatments, and recommendations are discussed. |
PMID: 26306366 [PubMed - indexed for MEDLINE] | |
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10. | Clin Exp Rheumatol. 2015 Jul-Aug;33(4):457-64. Epub 2015 Jun 19.
Myositis in primary Sjögren's syndrome: data from a multicentre cohort.Colafrancesco S1, Priori R1, Gattamelata A1, Picarelli G1, Minniti A1, Brancatisano F1, D'Amati G2, Giordano C2, Cerbelli B2, Maset M3, Quartuccio L3, Bartoloni E4, Carubbi F5, Cipriani P5, Baldini C6, Luciano N6, De Vita S3, Gerli R4, Giacomelli R5, Bombardieri S6, Valesini G1.
Author information:
AbstractOBJECTIVES:In primary Sjögren's syndrome (pSS), muscle pain and/or muscular weakness is relatively frequent while myositis has been reported in 3% of patients. The aim of this study was to describe the prevalence of myositis in a multicentre Italian pSS cohort and to address the clinical manifestations, histological findings and therapeutic strategies. METHODS:Clinical, serological and therapeutic data from a pSS cohort of patients were retrospectively collected. According to Bohan and Peter's criteria, inflammatory myopathy (IM) was suspected in case of muscular weakness associated with increased creatine-phosphokinase (CPK) or abnormal electromyography (EMG). When performed, muscle biopsies were analysed. RESULTS:In a cohort of 1320 patients, 17 (1.28%) presented muscular weakness [in some cases myalgias (7/17, 41.1%)], accompanied by increased CPK [13/17, (76.4%)] and/or abnormal EMG [13/14, (92.8%)]. Ten out of 17 (58.8%) fulfilled at least three diagnostic criteria for IM. Muscular biopsy was performed in 13/17 (76.4%) cases with histologically confirmed myositis in 6/13 (46.1%) (1"IBM-like"-5"PM-like"). In two "PM-like" cases, several fibres showed a decreased histochemical cytochrome C oxidase (COX) stain. Two biopsies tested "negative", four showed "non-specific" findings. All patients were treated with corticosteroids followed by different DMARDs. CONCLUSIONS:Our retrospective analysis shows a prevalence of myositis in pSS lower than previously reported, mainly appearing as an overlapping syndrome. Histological findings confirm the possible presence of an IBM or of a myopathy more similar to PM with a decreased COX activity. Classical immunosuppressants are effective although in most difficult cases IVIg or RTX may be used with benefit. |
PMID: 26088683 [PubMed - indexed for MEDLINE] | |
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11. | Surv Ophthalmol. 2015 May-Jun;60(3):183-95. doi: 10.1016/j.survophthal.2014.10.001. Epub 2014 Oct 16.
Retinoic acid and the ocular surface.Samarawickrama C1, Chew S2, Watson S3.
Author information:
AbstractRetinoic acid is known to improve cutaneous wound healing and, in recent years, its application in ophthalmology has been investigated. This review looks at the role of retinoic acid on the ocular surface. Retinoic acid can be produced synthetically, and its mechanism of action includes both nuclear and non-nuclear receptor mediated pathways. It has been shown to improve full and partial thickness corneal lacerations as well as corneal epithelial defects. Retinoic acid plays a critical role in cell differentiation at the cornea, conjunctiva, and limbus, and may have an anti-tumor role. Its positive effect is only achieved at the correct concentration, however; excess concentrations of retinoic acid have a deleterious effect. The main limiting factor of retinoic acid use is its detrimental effect on meibomian glands, resulting in cell death, atrophy of acini, hyposecretion of oils, and altered gene expression, eventually resulting in dry eye symptoms. This effect is reversible on discontinuation of the drug. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved. |
PMID: 25890622 [PubMed - indexed for MEDLINE] | |
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12. | Clin Exp Immunol. 2015 Aug;181(2):244-52. doi: 10.1111/cei.12638.
Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells.Katsiougiannis S1,2, Tenta R1, Skopouli FN1,3.
Author information:
AbstractThe aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sjögren's syndrome (SS) autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/Sjögren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens. © 2015 British Society for Immunology. |
PMID: 25845745 [PubMed - indexed for MEDLINE] | |
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13. | Ann Otol Rhinol Laryngol. 2015 Sep;124(9):721-7. doi: 10.1177/0003489415579911. Epub 2015 Apr 3.
The Quality of Life Burden Associated With Voice Disorders in Sjögren's Syndrome.Tanner K1, Pierce JL2, Merrill RM3, Miller KL4, Kendall KA5, Roy N2.
Author information:
AbstractOBJECTIVES:This study examined quality of life burden of voice disorders in Sjögren's syndrome (SS). METHODS:Patients with SS (n = 101) completed interviews involving patient-reported histories of voice disorders, specific voice symptoms, SS disease severity, the Voice-Related Quality of Life (V-RQOL), and the general health-related quality of life Short Form 36 (SF-36) questionnaires. Relationships among voice symptoms, disease severity, and quality-of-life measures were examined and compared with patient-reported voice disorders. RESULTS:Significant correlations were observed among voice symptoms, disease severity, V-RQOL, SF-36, and patient-reported voice disorders (P < .05). Patients with SS who reported a voice disorder experienced a greater burden on general quality of life as compared with those without voice disorders. Specific voice symptoms significantly correlated with reduced SF-36 scores included frequent throat-clearing, throat soreness, difficulty projecting, and vocal discomfort. Despite the added burden of a voice disorder on quality of life in SS, voice-related treatment seeking was low (15.8%). However, the majority of patients who received voice treatment reported voice improvement. CONCLUSIONS:Individuals with SS frequently experience voice disorders and specific voice-related symptoms that are associated with reduced quality of life. These findings have important implications for voice referral practices and voice disorder symptom management in this population. © The Author(s) 2015. |
PMID: 25841042 [PubMed - indexed for MEDLINE] | |
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14. | Rheumatology (Oxford). 2015 Aug;54(8):1429-34. doi: 10.1093/rheumatology/kev005. Epub 2015 Mar 3.
Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren's syndrome.Pontarini E1, Fabris M2, Quartuccio L3, Cappeletti M4, Calcaterra F4, Roberto A1, Curcio F5, Mavilio D6, Della Bella S4, De Vita S3.
Author information:
AbstractOBJECTIVE:The aim of this study was to investigate the biological effects of belimumab on B cells in the first phase II open-label trial with belimumab in patients with primary SS (pSS) (BELISS). METHODS:Peripheral blood B cell subsets and their B cell activating factor-receptor (BAFF-R) expression were analysed by multicolour flow cytometry in 10 pSS patients either before or after 24 and 52 weeks of therapy with belimumab. Serum BAFF levels were analysed by ELISA. RESULTS:At baseline, pSS patients showed a significant increase in circulating B cells compared with healthy donors matched for age and sex, with a predominant expansion of transitional and naive B cell subsets. pSS patients also showed higher serum BAFF levels and lower B cell BAFF-R expression. Therapy with belimumab in pSS patients induced a significant reduction in transitional and naive B cell subsets to levels similar to those observed in healthy donors. Furthermore, belimumab normalized BAFF-R expression in all B subsets comprised within the memory compartment. The restoration of B cell frequency and subset composition in response to belimumab was also associated with a decrease in serum levels of Ig, RF, ANAs, and with an increase in the C4 complement fraction. All of these belimumab-mediated effects were observed after 24 weeks of therapy and maintained until the end of the therapeutic protocol. CONCLUSION:Taken together, our findings show that targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS. TRIAL REGISTRATION:clinicaltrials.gov; https://clinicaltrials.gov/; NCT01008982. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
PMID: 25740829 [PubMed - indexed for MEDLINE] | |
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15. | J Intern Med. 2015 Aug;278(2):185-92. doi: 10.1111/joim.12346. Epub 2015 Feb 3.
Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.Bartoloni E1, Baldini C2, Schillaci G3, Quartuccio L 4, Priori R5, Carubbi F6, Bini V7, Alunno A1, Bombardieri S2, De Vita S4, Valesini G5, Giacomelli R6, Gerli R1.
Author information:
AbstractOBJECTIVE:Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS). METHODS:We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS:Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS:pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events. © 2015 The Association for the Publication of the Journal of Internal Medicine. |
PMID: 25582881 [PubMed - indexed for MEDLINE] | |
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16. | Rev Bras Reumatol. 2014 Mar-Apr;54(2):131-9.
Incidence of neoplasms in the most prevalent autoimmune rheumatic diseases: a systematic review.[Article in English, Portuguese]
Machado RI1, Braz Ade S2, Freire EA2.
Author information:
AbstractThis article is a systematic review of the literature about the coexistence of cancer and autoimmune rheumatic diseases, their main associations, cancers and possible risk factors associated, with emphasis on existing population-based studies, besides checking the relation of this occur with the use of the drugs used in the treatment of autoimmune diseases. A search was conducted of scientific articles indexed in the Cochrane / BVS, Pubmed / Medline and Scielo / Lilacs in the period from 2002 to 2012. Also consulted was the IB-ICT (Brazilian digital library of theses and Masters), with descriptors in Portuguese and English for "Systemic sclerosis", "Rheumatoid Arthritis", " Systemic Lupus Erythematosus" and "Sjögren's syndrome", correlating each one with the descriptor AND "neoplasms". The results showed that in the database IBICT a thesis and a dissertation for the descriptor SLE met the inclusion criteria, none met RA one thesis to SS. Lilacs in the database/Scielo found two articles on "Rheumatoid Arthritis" AND "neoplasms". In Pubmed/Medline the inicial search resulted in 118 articles, and 41 were selected. The review noted the relationship between cancer and autoimmune rheumatic diseases, as well as a risk factor for protection, although the pathophysiological mechanisms are not known. |
PMID: 24878860 [PubMed - indexed for MEDLINE] | |
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17. | Indian J Ophthalmol. 2014 May;62(5):654-5. doi: 10.4103/0301-4738.118428.
Tear function and ocular surface after Muller muscle-conjunctival resection.Author information:
AbstractMuller muscle-conjunctival resection (MCR) is a surgical technique to correct mild and moderate ptosis. In this study, tear function tests and ocular surface are evaluated in patients who underwent unilateral surgery. Sixteen patients with normal preoperative tear function who underwent unilateral MCR were evaluated prospectively. The fellow eyes of the patients were taken as the control group. A dry eye assessment questionnaire, Schirmer testing, tear film break-up time, fluorescein stain, Rose-Bengal stain, and conjunctival impression cytology were used to assess the tear film functions and ocular surface changes in the operated and non-operated eyes. There was no statistically significant difference in the tear function tests and goblet cell densities between the operated and non-operated eyes. The results indicate that an MCR procedure has no apparent effect on tear function tests and goblet cell density in patients with normal preoperative tear function. |
PMID: 24088631 [PubMed - indexed for MEDLINE] | |
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18. | Oral Dis. 2014 Mar;20(2):153-61. doi: 10.1111/odi.12105. Epub 2013 Apr 5.
Oral manifestations and their treatment in Sjögren's syndrome.Author information:
AbstractSjögren's syndrome (SS) is a complex, chronic, systemic, autoimmune disease that mainly affects the exocrine glands, especially the salivary and lacrimal glands, leading to dryness of the oral and ocular mucosae. Several factors have been studied that could explain the glandular hypofunction primarily related to water transport. Recent reports have shown alterations in secretory route and trafficking in labial salivary glands, explaining alterations in the saliva quality. The decrease in salivary flow and qualitative alterations in saliva could explain many of the oral manifestations. The exocrine manifestations and systemic involvement significantly impact the patient's perception of health-related quality of life. For this reason and given its systemic nature, the treatment of these patients should be multidisciplinary. This review addresses some particular oral health aspects of SS patients and focuses on relevant topics concerning the treatment and prevention of common oral disorders associated with this disease. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
PMID: 23557026 [PubMed - indexed for MEDLINE] | |
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NEW PUBLICATIONS ONTO SEPT. 25TH 2015
NEW PUBLICATIONS ONTO SEPT. 25TH 2015
The Scientific World Journal is a peer-reviewed, open access journal covering a wide range of subjects in science, technology, and medicine. The journal's Editorial Board as well as its Table of Contents are divided into 98 subject areas that are covered within the journal's scope.
http://www.hindawi.com
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Br J Ophthalmol. 2015 Sep 16. pii: bjophthalmol-2015-307094. doi: 10.1136/bjophthalmol-2015-307094. [Epub ahead of print]
Incomplete response to artificial tears is associated with features of neuropathic ocular pain.Galor A1, Batawi H1, Felix ER2, Margolis TP3 , Sarantopoulos KD4, Martin ER5, Levitt RC6.
Author information:
AbstractAIMS:Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. METHODS:Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. RESULTS:By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. CONCLUSIONS:Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
PMID: 26377416 [PubMed - as supplied by publisher] | |
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2. | Eye Contact Lens. 2015 Sep 14. [Epub ahead of print]
Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review.Author information:
AbstractDry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses. |
PMID: 26372476 [PubMed - as supplied by publisher] | |
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3. | J Fr Ophtalmol. 2015 Sep 11. pii: S0181-5512(15)00249-1. doi: 10.1016/j.jfo.2015.02.008. [Epub ahead of print]
[Cyclosporine eye drops: A 4-year retrospective study (2009-2013)].[Article in French]
Author information:
AbstractINTRODUCTION:The University Hospitals Paris Centre Pharmacy compounds three concentrations of cyclosporine eye drops: 20mg/mL (=2%); 5mg/mL (=0.5%) and 0.5mg/mL (=0.05%). Cyclosporine A 2% drops were developed in 1995 to prevent the rejection of high-risk cornea transplants after failure of topical steroids. The other concentrations of eye drops were developed for the treatment of various immune or inflammatory diseases of the cornea, conjunctiva and uvea. These eye drops are dispensed with a physician's prescription to hospitalized or ambulatory patients. A retrospective study over 4 years (2009-2013) was conducted to analyze the details of prescription and possible adverse events. MATERIALS AND METHODS:Dispensations made from January 1st, 2009 through December 31st, 2013 were studied, including patient age, dose of cyclosporine and practice location of prescribing physician. We also recorded the indications for cyclosporine eye drops in a sample of ambulatory patients. The analysis of local tolerability and the effect on visual comfort was based on questionnaires sent to the patients on cyclosporine 2% over a period of 2 months. RESULTS:Cyclosporine eye drops prescription grew continuously from 2009 through 2013 for all concentrations. In 2013, 5859patients were treated, among which 3616patients with topical cyclosporine 2%, 1681patients with 0.5%, and 562 patients with 0.05%. In total, this represents 62,621 eye drops. Treated patients ranged from 1 week to 100 years old. Topical 2% cyclosporine is indicated in 61% of cases to prevent high-risk corneal graft rejection. Other indications are corneal ulcer (6%), atopic keratoconjunctivitis (5%), vernal keratoconjunctivitis (5%) and herpetic keratitis (4%). Topical 0.5% cyclosporine is prescribed primarily for dry eye syndrome (20%) and to prevent rejection of high-risk corneal transplantation (11%), to treat ocular rosacea (10%), vernal keratoconjunctivitis (10%), atopic keratoconjunctivitis (8%) and Sjögren's syndrome (7%). Topical 0.05% cyclosporine is prescribed primarily for dry eye syndrome resistant to conventional treatment (47%) and Sjögren's syndrome (21%). Local tolerability of topical cyclosporine was evaluated in 388 patients. The majority of patients (63%) did not experience any adverse effects. The main side effects are redness, burning sensation and itching. CONCLUSION:Prescription of various formulations of topical cyclosporine is current practice for surgical indications: rejection of high-risk corneal transplantation; or medical indications: vernal or atopic keratoconjunctivitis and dry eye syndrome. Further prospective randomized studies would be necessary to validate formulations, doses and indications of cyclosporine eye drops. Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
PMID: 26371985 [PubMed - as supplied by publisher] | |
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4. | Ophthalmologica. 2015 Sep 15. [Epub ahead of print]
Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy.Author information:
AbstractPURPOSE:Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. MATERIAL AND METHODS:In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. RESULTS:Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. CONCLUSION:SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases. © 2015 S. Karger AG, Basel. |
PMID: 26368551 [PubMed - as supplied by publisher] | |
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5. | Chin Med J (Engl). 2015 20th Sep;128(18):2444-2449. doi: 10.4103/0366-6999.164927.
Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications.Author information:
AbstractBACKGROUND:Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. METHODS:Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91. RESULTS:Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = -3.843, P < 0.001, and z = -3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = -10.994, P < 0.001) and aqueous tear production (t-test: t = -10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = -9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment. CONCLUSIONS:SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment. |
PMID: 26365960 [PubMed - as supplied by publisher] | |
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6. | Ophthalmology. 2015 Sep 10. pii: S0161-6420(15)00777-0. doi: 10.1016/j.ophtha.2015.08.001. [Epub ahead of print]
Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study.Tauber J1, Karpecki P2, Latkany R3, Luchs J4, Martel J5, Sall K6, Raychaudhuri A7, Smith V7, Semba CP7; OPUS-2 Investigators.
Author information:
AbstractPURPOSE:Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. DESIGN:A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. PARTICIPANTS:Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0-4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0-100 visual analogue scale [VAS]). METHODS:Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES:Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in study eye. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS:A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, -0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious. CONCLUSIONS:Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
PMID: 26365210 [PubMed - as supplied by publisher] | |
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7. | Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4336-49. doi: 10.1167/iovs.15-17088.
A New Recombinant PACAP-Derived Peptide Efficiently Promotes Corneal Wound Repairing and Lacrimal Secretion.Author information:
AbstractPURPOSE:A new recombinant pituitary adenylate cyclase-activating polypeptide (PACAP)-derived peptide, MPAPO, which has higher stability and PAC1-specific potency, was generated. The actions of MPAPO on corneal wound repairing and lacrimal secretion were examined. METHODS:MPAPO was prepared and identified by gene recombination, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). Stability assay was performed by HPLC-ESI-MS. PAC1-specific binding and potency assays were performed using PAC1-CHO cells. C57BL/6 mice and Japanese white rabbits were respectively used to analyze the effects of MPAPO on corneal wound repairing and lacrimal fluid secretion. Tetrazolium-based colorimetric assay (MTT), immunofluorescence, gene microarrays, and Western blot assay were performed to measure the effects of MPAPO on corneal epithelial cell proliferation, synapse growth, and gene differential expression of trigeminal ganglion cells. RESULTS:As compared with the wild PACAP, the in vitro stability and PAC1-specific potency of MPAPO with four mutations (M17L, L27K and M, K, respectively, added to the N- and C-terminus) were increased approximately 31- and 2-fold, respectively. MPAPO can significantly promote the proliferation of mouse corneal epithelium cells and the synapse growth of trigeminal ganglion cells. In experimental animals, MPAPO performed a complete corneal epithelial wound closure in 30 hours and significantly inhibited corneal neovascularization, and the effects were obviously stronger than for wild PACAP and recombinant bovine (rb)-bFGF (an anti-corneal wound drug). Furthermore, MPAPO can increase the lacrimal secretion, which may efficiently improve dry eye. CONCLUSIONS:MPAPO may represent a promising external therapeutic peptide for corneal wound repairing or dry eye. |
PMID: 26176871 [PubMed - indexed for MEDLINE] | |
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8. | Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4186-97. doi: 10.1167/iovs.14-15496.
IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells.Author information:
AbstractPURPOSE:To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes. METHODS:Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 μL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days. Subsequently, cell proliferation was assessed or cultures were immunostained, collected for dot blot, or for reverse transcription (RT) and quantitative real-time PCR (qPCR) or for RT-PCR gene array. RESULTS:The cultured conjunctival epithelium expressed goblet cell associated keratin 7 and mucins MUC5AC and MUC2 and when stimulated with IL-13 showed increased proliferation at D3 and D7 (P < 0.05) compared with control. MUC5AC expression was increased in the IL-13-treated group at D3 and D14 (P < 0.05). IL-13-treated cultures showed increased chemokine ligand 26 (CCL26), chloride channel calcium activated channel 3 (CLCA3), fas ligand (FasL), and Relm-β at D7. All conjunctival cultures expressed MUC2, and its expression was decreased at D3 (P < 0.05) and increased at D14 (P < 0.05) with IL-13 treatment. CONCLUSIONS:This study demonstrated that conjunctival goblet cells are IL-13 responsive cells that produce factors known to maintain epithelial barrier, stimulate mucin production, and modulate immune response in nonocular mucosa when treated with IL-13. The functional significance of IL-13-stimulated factors remains to be determined. |
PMID: 26132778 [PubMed - indexed for MEDLINE] | |
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9. | Respir Care. 2015 Apr;60(4):e90-1. doi: 10.4187/respcare.03972.
Mechanical ventilation for the treatment of severe excessive dynamic airway collapse.Bastos HN1, Teixeira N2, Redondo M2, Gonçalves M3, Sucena M2.
Author information:
Comment in
Comment on |
PMID: 25841047 [PubMed - indexed for MEDLINE] | |
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10. | J Cataract Refract Surg. 2015 Mar;41(3):652-65. doi: 10.1016/j.jcrs.2015.02.006.
Small-incision lenticule extraction.Moshirfar M1, McCaughey MV2, Reinstein DZ2, Shah R2, Santiago-Caban L2, Fenzl CR2.
Author information:
AbstractThis review looks at the benefits, limitations, complications, and future applications of the small-incision lenticule extraction procedure. Using the search terms small incision lenticule extraction and femtosecond lenticule extraction, we obtained data from 56 articles (omitting German and Chinese articles) from the PubMed database. Small-incision lenticule extraction has shown efficacy, predictability, and safety that are proportionate to those of laser in situ keratomileusis (LASIK), with the additional benefit that it eliminates flap creation and the attendant risks. The potential advantages of the procedure related to improved biomechanical stability, postoperative inflammation, and dry-eye symptoms have not been fully established. Small-incision lenticule extraction-treated eyes have shown a reduced degree of postoperative corneal denervation and higher-order aberrations and an accelerated rate of corneal nerve convalescence relative to LASIK. Future possibilities related to long-term cryogenic storage of extracted lenticules with eventual reimplantation or donation have been investigated with encouraging preliminary results. FINANCIAL DISCLOSURE:Drs. Reinstein and Shah are consultants to Carl Zeiss Meditec AG. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved. |
PMID: 25804585 [PubMed - indexed for MEDLINE] | |
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11. | J Clin Rheumatol. 2015 Jan;21(1):31-2. doi: 10.1097/RHU.0000000000000210.
Refractory primary Sjögren syndrome successfully treated with bortezomib.Author information:
AbstractPrimary Sjögren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS. |
PMID: 25539431 [PubMed - indexed for MEDLINE] | |
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12. | Arthritis Res Ther. 2014 Feb 11;16(1):R51. doi: 10.1186/ar4481.
Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.Hershberg U, Meng W, Zhang B, Haff N, St Clair EW, Cohen PL, McNair PD, Li L, Levesque MC, Luning Prak ET.
AbstractINTRODUCTION:Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. METHODS:To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. RESULTS:Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. CONCLUSIONS:For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means of measuring the chronicity and selection of expanded B-cell populations in humans. |
PMID: 24517398 [PubMed - indexed for MEDLINE] | |
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13. | Arthritis Res Ther. 2014 Feb 6;16(1):R46. doi: 10.1186/ar4475.
Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren's syndrome and rheumatoid arthritis.AbstractINTRODUCTION:Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease. METHODS:FC was measured in consecutive patients with SSc, primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated. RESULTS:FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects. CONCLUSIONS:FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced. |
PMID: 24499541 [PubMed - indexed for MEDLINE] | |
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NEW PUBLICATIONS UPTO SEPTEMBER 18TH 2015
Long-term use of topical drugs can induce changes in theconjunctiva and ocular surface. To determine theconjunctival changes resulting from topical glaucomamedication, patients with glaucoma were selected andclassified into seven groups, according to the medicationreceived: 24 eyes were treated with betaxolol, 20 eyes withlevobunolol, 32 eyes with timolol maleate, 22 eyes withpilocarpine, 52 eyes with beta-blocker and pilocarpine, 34eyes with beta-blocker and dipivefrin, and 32 eyes withmaximum therapy.
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1. | Br J Ophthalmol. 2015 Sep 16. pii: bjophthalmol-2015-307094. doi: 10.1136/bjophthalmol-2015-307094. [Epub ahead of print]
Incomplete response to artificial tears is associated with features of neuropathic ocular pain.Galor A1, Batawi H1, Felix ER2, Margolis TP3 , Sarantopoulos KD4, Martin ER5, Levitt RC6.
Author information:
AbstractAIMS:Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. METHODS:Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. RESULTS:By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. CONCLUSIONS:Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
PMID: 26377416 [PubMed - as supplied by publisher] | |
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2. | Eye Contact Lens. 2015 Sep 14. [Epub ahead of print]
Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review.Author information:
AbstractDry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses. |
PMID: 26372476 [PubMed - as supplied by publisher] | |
Similar articles | |
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3. | J Fr Ophtalmol. 2015 Sep 11. pii: S0181-5512(15)00249-1. doi: 10.1016/j.jfo.2015.02.008. [Epub ahead of print]
[Cyclosporine eye drops: A 4-year retrospective study (2009-2013)].[Article in French]
Author information:
AbstractINTRODUCTION:The University Hospitals Paris Centre Pharmacy compounds three concentrations of cyclosporine eye drops: 20mg/mL (=2%); 5mg/mL (=0.5%) and 0.5mg/mL (=0.05%). Cyclosporine A 2% drops were developed in 1995 to prevent the rejection of high-risk cornea transplants after failure of topical steroids. The other concentrations of eye drops were developed for the treatment of various immune or inflammatory diseases of the cornea, conjunctiva and uvea. These eye drops are dispensed with a physician's prescription to hospitalized or ambulatory patients. A retrospective study over 4 years (2009-2013) was conducted to analyze the details of prescription and possible adverse events. MATERIALS AND METHODS:Dispensations made from January 1st, 2009 through December 31st, 2013 were studied, including patient age, dose of cyclosporine and practice location of prescribing physician. We also recorded the indications for cyclosporine eye drops in a sample of ambulatory patients. The analysis of local tolerability and the effect on visual comfort was based on questionnaires sent to the patients on cyclosporine 2% over a period of 2 months. RESULTS:Cyclosporine eye drops prescription grew continuously from 2009 through 2013 for all concentrations. In 2013, 5859patients were treated, among which 3616patients with topical cyclosporine 2%, 1681patients with 0.5%, and 562 patients with 0.05%. In total, this represents 62,621 eye drops. Treated patients ranged from 1 week to 100 years old. Topical 2% cyclosporine is indicated in 61% of cases to prevent high-risk corneal graft rejection. Other indications are corneal ulcer (6%), atopic keratoconjunctivitis (5%), vernal keratoconjunctivitis (5%) and herpetic keratitis (4%). Topical 0.5% cyclosporine is prescribed primarily for dry eye syndrome (20%) and to prevent rejection of high-risk corneal transplantation (11%), to treat ocular rosacea (10%), vernal keratoconjunctivitis (10%), atopic keratoconjunctivitis (8%) and Sjögren's syndrome (7%). Topical 0.05% cyclosporine is prescribed primarily for dry eye syndrome resistant to conventional treatment (47%) and Sjögren's syndrome (21%). Local tolerability of topical cyclosporine was evaluated in 388 patients. The majority of patients (63%) did not experience any adverse effects. The main side effects are redness, burning sensation and itching. CONCLUSION:Prescription of various formulations of topical cyclosporine is current practice for surgical indications: rejection of high-risk corneal transplantation; or medical indications: vernal or atopic keratoconjunctivitis and dry eye syndrome. Further prospective randomized studies would be necessary to validate formulations, doses and indications of cyclosporine eye drops. Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
PMID: 26371985 [PubMed - as supplied by publisher] | |
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4. | Ophthalmologica. 2015 Sep 15. [Epub ahead of print]
Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy.Author information:
AbstractPURPOSE:Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. MATERIAL AND METHODS:In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. RESULTS:Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. CONCLUSION:SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases. © 2015 S. Karger AG, Basel. |
PMID: 26368551 [PubMed - as supplied by publisher] | |
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5. | Chin Med J (Engl). 2015 20th Sep;128(18):2444-2449. doi: 10.4103/0366-6999.164927.
Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications.Author information:
AbstractBACKGROUND:Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. METHODS:Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91. RESULTS:Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = -3.843, P < 0.001, and z = -3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = -10.994, P < 0.001) and aqueous tear production (t-test: t = -10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = -9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment. CONCLUSIONS:SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment. |
PMID: 26365960 [PubMed - as supplied by publisher] | |
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6. | Ophthalmology. 2015 Sep 10. pii: S0161-6420(15)00777-0. doi: 10.1016/j.ophtha.2015.08.001. [Epub ahead of print]
Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study.Tauber J1, Karpecki P2, Latkany R3, Luchs J4, Martel J5, Sall K6, Raychaudhuri A7, Smith V7, Semba CP7; OPUS-2 Investigators.
Author information:
AbstractPURPOSE:Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. DESIGN:A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. PARTICIPANTS:Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0-4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0-100 visual analogue scale [VAS]). METHODS:Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES:Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in study eye. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS:A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, -0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious. CONCLUSIONS:Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
PMID: 26365210 [PubMed - as supplied by publisher] | |
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7. | Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4336-49. doi: 10.1167/iovs.15-17088.
A New Recombinant PACAP-Derived Peptide Efficiently Promotes Corneal Wound Repairing and Lacrimal Secretion.Author information:
AbstractPURPOSE:A new recombinant pituitary adenylate cyclase-activating polypeptide (PACAP)-derived peptide, MPAPO, which has higher stability and PAC1-specific potency, was generated. The actions of MPAPO on corneal wound repairing and lacrimal secretion were examined. METHODS:MPAPO was prepared and identified by gene recombination, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). Stability assay was performed by HPLC-ESI-MS. PAC1-specific binding and potency assays were performed using PAC1-CHO cells. C57BL/6 mice and Japanese white rabbits were respectively used to analyze the effects of MPAPO on corneal wound repairing and lacrimal fluid secretion. Tetrazolium-based colorimetric assay (MTT), immunofluorescence, gene microarrays, and Western blot assay were performed to measure the effects of MPAPO on corneal epithelial cell proliferation, synapse growth, and gene differential expression of trigeminal ganglion cells. RESULTS:As compared with the wild PACAP, the in vitro stability and PAC1-specific potency of MPAPO with four mutations (M17L, L27K and M, K, respectively, added to the N- and C-terminus) were increased approximately 31- and 2-fold, respectively. MPAPO can significantly promote the proliferation of mouse corneal epithelium cells and the synapse growth of trigeminal ganglion cells. In experimental animals, MPAPO performed a complete corneal epithelial wound closure in 30 hours and significantly inhibited corneal neovascularization, and the effects were obviously stronger than for wild PACAP and recombinant bovine (rb)-bFGF (an anti-corneal wound drug). Furthermore, MPAPO can increase the lacrimal secretion, which may efficiently improve dry eye. CONCLUSIONS:MPAPO may represent a promising external therapeutic peptide for corneal wound repairing or dry eye. |
PMID: 26176871 [PubMed - indexed for MEDLINE] | |
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8. | Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4186-97. doi: 10.1167/iovs.14-15496.
IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells.Author information:
AbstractPURPOSE:To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes. METHODS:Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 μL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days. Subsequently, cell proliferation was assessed or cultures were immunostained, collected for dot blot, or for reverse transcription (RT) and quantitative real-time PCR (qPCR) or for RT-PCR gene array. RESULTS:The cultured conjunctival epithelium expressed goblet cell associated keratin 7 and mucins MUC5AC and MUC2 and when stimulated with IL-13 showed increased proliferation at D3 and D7 (P < 0.05) compared with control. MUC5AC expression was increased in the IL-13-treated group at D3 and D14 (P < 0.05). IL-13-treated cultures showed increased chemokine ligand 26 (CCL26), chloride channel calcium activated channel 3 (CLCA3), fas ligand (FasL), and Relm-β at D7. All conjunctival cultures expressed MUC2, and its expression was decreased at D3 (P < 0.05) and increased at D14 (P < 0.05) with IL-13 treatment. CONCLUSIONS:This study demonstrated that conjunctival goblet cells are IL-13 responsive cells that produce factors known to maintain epithelial barrier, stimulate mucin production, and modulate immune response in nonocular mucosa when treated with IL-13. The functional significance of IL-13-stimulated factors remains to be determined. |
PMID: 26132778 [PubMed - indexed for MEDLINE] | |
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9. | Respir Care. 2015 Apr;60(4):e90-1. doi: 10.4187/respcare.03972.
Mechanical ventilation for the treatment of severe excessive dynamic airway collapse.Bastos HN1, Teixeira N2, Redondo M2, Gonçalves M3, Sucena M2.
Author information:
Comment in
Comment on |
PMID: 25841047 [PubMed - indexed for MEDLINE] | |
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10. | J Cataract Refract Surg. 2015 Mar;41(3):652-65. doi: 10.1016/j.jcrs.2015.02.006.
Small-incision lenticule extraction.Moshirfar M1, McCaughey MV2, Reinstein DZ2, Shah R2, Santiago-Caban L2, Fenzl CR2.
Author information:
AbstractThis review looks at the benefits, limitations, complications, and future applications of the small-incision lenticule extraction procedure. Using the search terms small incision lenticule extraction and femtosecond lenticule extraction, we obtained data from 56 articles (omitting German and Chinese articles) from the PubMed database. Small-incision lenticule extraction has shown efficacy, predictability, and safety that are proportionate to those of laser in situ keratomileusis (LASIK), with the additional benefit that it eliminates flap creation and the attendant risks. The potential advantages of the procedure related to improved biomechanical stability, postoperative inflammation, and dry-eye symptoms have not been fully established. Small-incision lenticule extraction-treated eyes have shown a reduced degree of postoperative corneal denervation and higher-order aberrations and an accelerated rate of corneal nerve convalescence relative to LASIK. Future possibilities related to long-term cryogenic storage of extracted lenticules with eventual reimplantation or donation have been investigated with encouraging preliminary results. FINANCIAL DISCLOSURE:Drs. Reinstein and Shah are consultants to Carl Zeiss Meditec AG. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved. |
PMID: 25804585 [PubMed - indexed for MEDLINE] | |
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11. | J Clin Rheumatol. 2015 Jan;21(1):31-2. doi: 10.1097/RHU.0000000000000210.
Refractory primary Sjögren syndrome successfully treated with bortezomib.Author information:
AbstractPrimary Sjögren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS. |
PMID: 25539431 [PubMed - indexed for MEDLINE] | |
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12. | Arthritis Res Ther. 2014 Feb 11;16(1):R51. doi: 10.1186/ar4481.
Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.Hershberg U, Meng W, Zhang B, Haff N, St Clair EW, Cohen PL, McNair PD, Li L, Levesque MC, Luning Prak ET.
AbstractINTRODUCTION:Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. METHODS:To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. RESULTS:Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. CONCLUSIONS:For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means of measuring the chronicity and selection of expanded B-cell populations in humans. |
PMID: 24517398 [PubMed - indexed for MEDLINE] | |
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13. | Arthritis Res Ther. 2014 Feb 6;16(1):R46. doi: 10.1186/ar4475.
Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren's syndrome and rheumatoid arthritis.AbstractINTRODUCTION:Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease. METHODS:FC was measured in consecutive patients with SSc, primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated. RESULTS:FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects. CONCLUSIONS:FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced. |
PMID: 24499541 [PubMed - indexed for MEDLINE] | |
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14. | Respir Care. 2014 Oct;59(10):e156-9. doi: 10.4187/respcare.02929. Epub 2013 Dec 31.
Severe excessive dynamic airway collapse in a patient with primary Sjögren's syndrome.Author information:
Comment in
AbstractAirway and cystic lung diseases can be observed in patients with Sjögren's syndrome. We report a case of such a patient suffering from respiratory failure due to recurrent episodes of right pneumothorax, requiring invasive mechanical ventilation. Despite thoracic drainage and adequate pneumothorax management, the patient could not be weaned from the ventilator. Fiberoptic bronchoscopy revealed severe central excessive dynamic airway collapse of the lower part of the trachea and proximal bronchi. The severity of airway collapse was maximal at the intermediate bronchus level, with a near-complete obstruction during expiration. Inspiratory and expiratory computed tomography studies confirmed the fiberoptic findings and suggested a possible expiratory posterior compression of the intermediate bronchus by parenchymal lung cysts. Stenting was considered, but the patient died from ventilator-associated pneumonia before the procedure could be performed. This case is the first description of severe central excessive dynamic airway collapse in a patient with primary Sjögren's syndrome complicated by diffuse airway and cystic lung disease. Copyright © 2014 by Daedalus Enterprises. |
PMID: 24381188 [PubMed - indexed for MEDLINE] | |
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NEW PUBLICATIONS UPTO SEPTEMBER 13TH 2015
Meibomian gland dysfunction (MGD) can lead to inflammation of the meibomian glands (meibomianitis) and excess oil in the tear film. Bacteria and other substances often accompany the oil, which causes a myriad of ocular surface complaints and signs. Here, we review the common causes of and treatments for meibomian gland dysfunction to help you to diagnose and treat this common condition.
http://www.reviewofoptometry.com
1. | J Ocul Pharmacol Ther. 2015 Sep;31(7):413-8. doi: 10.1089/jop.2015.0017. Epub 2015 May 26.
TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sjögren's Syndrome Pathogenesis.Terzulli M1, Ruiz LC2, Kugadas A1, Masli S2, Gadjeva M1.
Author information:
AbstractPURPOSE:The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1(-/-)) mice, a strain that develops Sjögren's syndrome-like disease. METHODS:Conjunctival swabs were collected from TSP-1(-/-) and C57BL/6 mice and analyzed for bacterial presence. Opsonophagocytosis of the bacterial conjunctival isolates derived from the aged TSP-1(-/-) mice by neutrophils derived from either TSP-1(-/-) or C57BL/6 bone marrow was evaluated. The bactericidal activities of TSP-1-derived peptide were examined. RESULTS:We found that in TSP-1(-/-) mice, the conjunctival colonization with Staphylococcus aureus and coagulase negative staphylococci sp (CNS) species was significantly increased with aging and preceded that of the wild-type C57BL/6 control mice. This correlated with increased neutrophil infiltration into the conjunctiva of the TSP-1(-/-) mice, suggesting that TSP-1 plays a significant role in regulating immunity to commensals. Accordingly, the TSP-1(-/-) PMNs opsonophagocytozed the ocular commensals less efficiently than the TSP-1-sufficient neutrophils. Furthermore, a TSP-1-derived peptide, 4N1K, exhibited significant antimicrobial activity when compared to a control peptide against commensal sp. CONCLUSION:These studies illustrate that alterations in the commensal frequency occur in the early stages of development of Sjögren's-like pathology and suggest that interventions that limit commensal outgrowth such as the use of TSP-1-derived peptides could be used for treatment during the early stages of the disease to reduce the commensal burden and ensuing inflammation. |
PMID: 26352162 [PubMed - in process] | |
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2. | Invest Ophthalmol Vis Sci. 2015 Sep 1;56(10):5888-95. doi: 10.1167/iovs.15-17249.
Improvement of Outcome Measures of Dry Eye by a Novel Integrin Antagonist in the Murine Desiccating Stress Model.Author information:
AbstractPURPOSE:We investigated the effects of GW559090, a novel, competitive, and high-affinity α4 integrin antagonist, in a murine model of dry eye. Through interaction with vascular cell adhesion molecule 1 (VCAM-1) and fibronectin α4β1 integrin is involved in leukocyte trafficking and activation. METHODS:Female C57BL/6 mice, aged 6 to 8 weeks, were subjected to desiccating stress (DS). Bilateral topical twice daily treatment with GW559090 was compared to vehicle-treated controls. Treatment was initiated at the time of DS induction. Treatment effects were assessed on corneal staining with Oregon Green Dextran (OGD) and expression of inflammatory markers in ocular surface tissues by real time PCR. Dendritic cell activation was measured in draining cervical lymph nodes (CLN) by flow cytometry. Separate groups of mice received GW559090 subcutaneously to evaluate the effects of systemic administration on corneal staining and cells in CLN. RESULTS:Topical GW559090 significantly reduced corneal uptake of OGD compared to vehicle-treated disease controls in a dose-dependent manner (1, 3, 10, and 30 mg/mL) with 30 mg/mL showing the greatest reduction in OGD staining. When administered topically, corneal expression of IL-1α, matrix metalloproteinase (MMP)-9, chemokine ligand 9 (CXCL9), and TGF-β1 was reduced in GW559090-treated eyes. Topical treatment with GW559090 decreased dendritic cell activation in lymph nodes. The effects on corneal staining and cellular composition in CLN were not reproduced by systemic administration of GW559090, suggestive of a local role for integrin antagonism in the treatment of dry eye. CONCLUSION:The novel α4 integrin antagonist, GW559090, improved outcome measures of corneal staining and ocular surface inflammation in this murine model of dry eye. These results indicate the potential of this novel agent for the treatment of dry eye disease. |
PMID: 26348638 [PubMed - in process] | |
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3. | Cont Lens Anterior Eye. 2015 Sep 4. pii: S1367-0484(15)30020-5. doi: 10.1016/j.clae.2015.08.002. [Epub ahead of print]
On the prescribing of oral doxycycline or minocycline by UK optometrists as part of management of chronic Meibomian Gland Dysfunction (MGD).Author information:
AbstractPURPOSE:To review the special pharmacology of tetracycline antibiotics as anti-inflammatory drugs for treatment of obstructive Meibomian gland disease (MGD) METHODS: PubMed was used as principal resource for articles, regardless of language, on doxycycline and minocycline with key interests being on their serum and tissue pharmacokinetics and their use in clinical studies as part of management of MGD. RESULTS:With oral dosing of between 50 and 200mg, peak blood levels of these antibiotics have been reported to be predictably dose-dependent at between 1 and 5 microgram/mL, with human tear film levels not being detectable with 100mg dosing of doxycycline but levels of 0.2microgram/mL with 200mg minocycline. That these two tetracycline antibiotics reach the conjunctiva is indicated by conjunctival pigmentary changes due to photosensitization after very long term use. Based the reported use in a range of clinical studies on MGD, dosing with these two antibiotics for MGD is likely to be useful at relatively low doses (e.g. 100mg for doxycycline or 50mg for minocycline, either at once or twice daily depending on severity at presentation and previous history) continued for 2 to 3 months, with the expected outcome being small-to-substantial decreases in abnormal appearance of the glands (from -4 to -89%) and increases in tear film stability (from 21 to 273%). CONCLUSIONS:Oral doxycycline and minocycline have predictable pharmacokinetics and have been reported to improve Meibomian gland dysfunction over a few months of use. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. |
PMID: 26347083 [PubMed - as supplied by publisher] | |
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4. | J Parasit Dis. 2015 Sep;39(3):448-51. doi: 10.1007/s12639-013-0364-8. Epub 2013 Oct 17.
Salvage of Theileria infected calves with clinical manifestation of exophthalmia.Singh SK1, Sudan V2, Sachan P1, Srivastava A1.
Author information:
AbstractTwo crossbred female calves aged between 30 and 35 days were presented with bilateral exophthalmia, inappetence, pyrexia and cachexia since last 15 days. Clinical examination revealed mainly bilateral exophthalmia with dry and pulpy cornea, generalized enlargement of superficial lymph nodes, pallor mucous, petechiae, high rectal temperature and sternal recumbency. The calves were severely infested with Hyalomma anatolicum anatolicum ticks and thin layer blood smears revealed presence of piroplasm in the RBCs, while lymph nodes aspirate smear examination revealed presence schizonts in the mononuclear cells. The calves were treated with buparvaquone; meloxicam, nandrolone decanoate and vitamins A, D3, E and H. From day second post-therapy a remarkable improvement in the clinical condition was noticed and substantial reduction in the both protruded eyeballs was noticed by 7 days post-therapy in the both calves. Further at day 47 post-therapy the one calf was free from the parasite on blood smear examination and right eye was retracted in its orbits with full of sight. Moreover the left eye was also retracted in its orbit but there was loss of sight and opacity developed in this eye. While, the other calf also revealed remarkable improvement in the clinical condition and both eye balls retracted completely into the orbit at day 30 post-therapy. But, at day 86 the calf developed microphthalmia and complete loss of sight in both eyes. It can be concluded that adjunction of antioxidants and hematopoietic agents may salvage the calves suffering from fatal theileriosis. |
PMID: 26345050 [PubMed] | |
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5. | Zhongguo Zhong Yao Za Zhi. 2015 Mar;40(6):1151-5.
[Experimental study on efficiency of Spanishneedles Herb eye drops in treating perimenopausal xerophthalmia in rabbits].[Article in Chinese]
AbstractOBJECTIVE:To investigate the efficiency of Spanishneedles Herb eye drops in treating perimenopausal xerophthalmia in rabbits. METHOD:Totally 36 rabbits (36 right eyes) were ovariectomized, and 2 months later divided into three groups: the experimental group (group A, n = 12) given Spanishneedles Herb eye drops, the control group (group B, n = 12) given PBS and the model group (group C, n = 12) given no drug. The Schirmer I test (SIT), fluorescent (FL), total tear protein, diastase activity, lactoferrin and lysozyme contents and confocal scanning microscopy were performed at before the treatment and at 1 w, 2 w, 1 mo, 2 mo after the treatment. RESULT:Before the treatment, There was no significant difference in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity between two groups. Two months later after the treatment, both the group B and the group A showed differences degrees of changes in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity compared with that before the treatment, with statistical differences (P < 0.05); At each time point, both groups revealed statistical differences in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity (1 < 0.05). Two months later alter the treatment, densities of basal epithelial cells and inflammatory cells in the group A were (4 122 ±416) cells/mm2 and (339 ± 131) cells/mm2, while that in the group B were (3 343 ± 424) cells/mm2 and (49 ± 17) cells/mm2, with statistical differences between them (P < 0.05). CONCLUSION:Spanishneedles Herb eye drops could effectively treat perimenopausal xerophthalmia in rabbit caused by sex hormones decline. |
PMID: 26226762 [PubMed - indexed for MEDLINE] | |
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6. | Acta Cardiol. 2015 Jun;70(3):373.
Atorvastatin-induced dermatomyositis in a 47-year-old woman with Sjögren's syndrome. |
PMID: 26226717 [PubMed - indexed for MEDLINE] | |
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7. | Invest Ophthalmol Vis Sci. 2015 May;56(5):3347-54. doi: 10.1167/iovs.15-16717.
Corneal sensitivity following lacrimal gland excision in the rat.Author information:
AbstractPURPOSE:Dry eye disease (DED) produces ocular pain and irritation, yet a detailed characterization of ocular sensitivity in a preclinical model of DED is lacking. The aim of the present study was to assess nociceptive behaviors in an aqueous tear deficiency model of DED in the rat. METHODS:Spontaneous blinking, corneal mechanical thresholds, and eye wipe behaviors elicited by hypertonic saline (5.0 M) were examined over a period of 8 weeks following the unilateral excision of either the exorbital lacrimal gland or of the exorbital and infraorbital lacrimal glands, and in sham surgery controls. The effect of topical proparacaine on spontaneous blinking and of systemic morphine (0.5-3.0 mg/kg, subcutaneous [SC]) on spontaneous blinking and eye wipe responses were also examined. RESULTS:Lacrimal gland excision resulted in mechanical hypersensitivity and an increase in spontaneous blinking in the ipsilateral eye over an 8-week period that was more pronounced after infra- and exorbital gland excision. The time spent eye wiping was also enhanced in response to hypertonic saline (5.0 M) at both 1- and 8-week time-points, but only in infra- and exorbital gland excised animals. Morphine attenuated spontaneous blinking, and the response to hypertonic saline in dry eye animals and topical proparacaine application reduced spontaneous blinking down to control levels. CONCLUSIONS:These results indicate that aqueous tear deficiency produces hypersensitivity in the rat cornea. In addition, the increase in spontaneous blinks and their reduction by morphine and topical anesthesia indicate the presence of persistent irritation elicited by the activation of corneal nociceptors. |
PMID: 26024120 [PubMed - indexed for MEDLINE] | |
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8. | Intern Med J. 2014 Dec;44(12a):1259-61. doi: 10.1111/imj.12611.
Autoimmune haemolytic anaemia as an initial presentation of primary Sjögren syndrome.Author information:
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PMID: 25442764 [PubMed - indexed for MEDLINE] | |
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9. | Med Clin (Barc). 2015 Jan 20;144(2):88-91. doi: 10.1016/j.medcli.2014.01.014. Epub 2014 Mar 15.
[Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].[Article in Spanish]
Author information:
AbstractAutoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved. |
PMID: 24636281 [Pub |
Melatonin inhibits the Migration of Colon Cancer RKO cells by Down-regulating MLCK Expression through Cross-talk with p38 MAPK
Melatonin inhibits the Migration of Colon Cancer RKO cells by Down-regulating Myosin Light Chain Kinase Expression through Cross-talk with p38 MAPK.
A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%).
https://www.readbyqxmd.com
Author information
- 1Laboratory of Molecular Biology and Department of Biochemistry, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China E-mail : wangyuan@ahmu.edu.cn and shenghuahrl@163.com.
Abstract
BACKGROUND:
Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms.
MATERIALS AND METHODS:
The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38).
RESULTS:
The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38.
CONCLUSIONS:
Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.
- PMID: 26320459
NEW PUBLICATIONS UPTO AUG. 31ST 2015 ON DRY EYE DIAGNOSIS AND THERAPEUTICS
NEW PUBLICATIONS UPTO AUG. 31ST 2015 ON DRY EYE DIAGNOSIS AND THERAPEUTICS
How chronic glaucoma treatment can give rise to ocular surface disease, and how you can treat them both. Mark B. Abelson, MD, CM, FRCSC, FARVO, and Ashley Lafond, Andover, Mass. 10/4/2011 As our patients age, an increased interest and heightened awareness of the changes occurring on the ocular surface is necessary.
http://www.reviewofophthalmology.com
1. | Jpn J Ophthalmol. 2015 Aug 27. [Epub ahead of print]
Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition.Author information:
AbstractPURPOSE:To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment. METHODS:Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. RESULTS:The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins. CONCLUSIONS:Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye. |
PMID: 26310103 [PubMed - as supplied by publisher] | |
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2. | Vestn Oftalmol. 2015 May-Jun;131(3):22-6.
[Dry eye syndrome in patients with primary open-angle glaucoma].[Article in Russian]
Boyko EV, Simakova IL, Yakushev DY, Ignat'Ev SA, Alekseev IB, Mel'Nikova NV, Alyab'Ev MV, Mal'Tsev DS.
AbstractAIM:to determine the frequency and severity of dry eye syndrome (DES) in primary open-angle glaucoma (POAG) patients that are newly diagnosed or already receiving beta blocker instillation therapy. MATERIAL AND METHODS:A total of 127 patients (190 eyes) with POAG were divided into two groups. Group 1 included 55 newly diagnosed patients (88 eyes), group 2-72 POAG patients (102 eyes) instilling timolol 0.5% twice daily into the affected eye. The control group included 20 patients (40 eyes) aged 60-88 years (73.6 ± 9.2 years on average) with early age-related cataract. RESULTS:DES was found in 69 POAG patients (79%) who was just starting their topical hypotensive therapy and 85 of those (84%) under treatment (p = 0.39). CONCLUSIONS:One should take into account when prescribing ocular hypotensive therapy that newly diagnosed POAG patients usually already suffer from a dry eye. The use of topical beta blockers that contain preservatives exacerbates dry eye signs and symptoms in these patients. |
PMID: 26310003 [PubMed - in process] | |
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3. | PLoS One. 2015 Aug 24;10(8):e0135629. doi: 10.1371/journal.pone.0135629. eCollection 2015.
The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye.Dienes L1, Kiss HJ1, Perényi K1, Szepessy Z1 , Nagy ZZ1, Barsi Á2, Acosta MC3, Gallar J3, Kovács I1.
Author information:
AbstractPURPOSE:To investigate the characteristics of ocular surface sensations and corneal sensitivity during the interblink interval before and after tear supplementation in dry eye patients. METHODS:Twenty subjects (41.88±14.37 years) with dry eye symptoms were included in the dry eye group. Fourteen subjects (39.13±11.27 years) without any clinical signs and/or symptoms of dry eye were included in the control group. Tear film dynamics was assessed by non-invasive tear film breakup time (NI-BUT) in parallel with continuous recordings of ocular sensations during forced blinking. Corneal sensitivity to selective stimulation of corneal mechano-, cold and chemical receptors was assessed using a gas esthesiometer. All the measurements were made before and 5 min after saline and hydroxypropyl-guar (HP-guar) drops. RESULTS:In dry eye patients the intensity of irritation increased rapidly after the last blink during forced blinking, while in controls there was no alteration in the intensity during the first 10 sec followed by an exponential increase. Irritation scores were significantly higher in dry eye patients throughout the entire interblink interval compared to controls (p<0.004). NI-BUT significantly increased after HP-guar (p = 0.003) but not after saline drops (p = 0.14). In both groups, either after saline or HP-guar the shape of symptom intensity curves remained the same with significantly lower irritation scores (p<0.004), however after HP-guar the decrease was significantly more pronounced (p<0.004). Corneal sensitivity to selective mechanical, cold and chemical stimulation decreased significantly in both groups after HP-guar (p<0.05), but not after saline drops (p>0.05). CONCLUSION:Ocular surface irritation responses due to tear film drying are considerably increased in dry eye patients compared to normal subjects. Although tear supplementation improves the protective tear film layer, and thus reduce unpleasant sensory responses, the rapid rise in discomfort is still maintained and might be responsible for the remaining complaints of dry eye patients despite the treatment. |
PMID: 26302222 [PubMed - in process] | |
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4. | BMC Res Notes. 2015 Aug 23;8(1):368. doi: 10.1186/s13104-015-1367-6.
Spectrum of digoxin-induced ocular toxicity: a case report and literature review.Renard D1, Rubli E2, Voide N3, Borruat FX4, Rothuizen LE5.
Author information:
AbstractBACKGROUND:Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION:Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION:This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis. |
PMID: 26298392 [PubMed - in process] | |
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5. | Community Dent Health. 2015 Mar;32(1):5-7.
Tackling a dry mouth: an oral health intervention for Sjögren's sufferers. |
PMID: 26263585 [PubMed - indexed for MEDLINE] | |
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6. | Chin J Dent Res. 2015 Jun;18(2):95-101.
Effects of Multi-glycosides of Tripterygium wilfordiion in the Treatment of Sjögren's Syndrome in the Non-obese Diabetic Mouse Model.AbstractOBJECTIVE:To investigate the effects of the multi-glycosides of Tripterygium wilfordii (GTW) on Sjögren's syndrome (SS) in the non-obese diabetic (NOD) mouse model. METHODS:Twenty-seven 8-week-old, female NOD mice were divided into the GTW group, the hydroxychloroquine (HCQ) group, and control (normal saline) group, and received corresponding treatment for 16 weeks. The treatment-induced changes in stimulated total saliva flow rate (STFR), level of serum anti-SSA/SSB, ratio of regulatory T (Treg) cells, histology of the submandibular gland (SMG) and the gene expression profile that is related to inflammation and autoimmunization were evaluated. RESULTS:Compared to the untreated (control) mice, STRF, SMG index and Treg/CD4+ cell ratio were significantly higher, whereas anti-SSA, anti-SSB and lymphoid foci were remarkably lower in GTW-treated mice. HCQ-treated mice showed similar results except SMG index was not different from the untreated mice. NOD mice showed 19.03% altered gene expression with maturation from the age of 8 weeks to 24 weeks. Treatment with HCQ and GTW reduced the change in gene expression to 13.09% and 7.14%, respectively. CONCLUSION:GTW is as effective as HCQ in the treatment of Sjögren's syndrome in the NOD mouse model. |
PMID: 26167547 [PubMed - indexed for MEDLINE] | |
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7. | Curr Opin Ophthalmol. 2015 Jul;26(4):319-24. doi: 10.1097/ICU.0000000000000171.
Scleral lens use in dry eye syndrome.Author information:
AbstractPURPOSE OF REVIEW:Dry eye syndrome can be difficult to manage in severe or refractory cases. In patients in whom traditional treatments have limited efficacy, alternative treatments may be considered for dry eye syndrome, including scleral lenses. The present review summarizes the evidence regarding scleral lens use in dry eye syndrome. RECENT FINDINGS:Scleral lenses have become a viable option for severe dry eye syndrome, and have been shown to be efficacious and well tolerated, with most reports citing improved visual acuity and relief of symptoms. Currently, there are 18 manufacturers of scleral lenses, although published reports on scleral lenses primarily focus on the BostonSight PROSE and the Jupiter Lens. SUMMARY:Scleral lenses are efficacious and well tolerated for use in severe dry eye syndrome. Further research is needed to compare different sizes and types of lenses, and to standardize outcome measures. |
PMID: 26058032 [PubMed - indexed for MEDLINE] | |
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8. | Curr Opin Ophthalmol. 2015 Jul;26(4):260-4. doi: 10.1097/ICU.0000000000000158.
Femtosecond laser refractive surgery: small-incision lenticule extraction vs. femtosecond laser-assisted LASIK.Author information:
AbstractPURPOSE OF REVIEW:Small-incision lenticule extraction (SMILE) is a novel technique devised to correct refractive errors. SMILE circumvents excimer laser photoablation of cornea, as the stromal lenticule cut by femtosecond laser is removed manually. Smaller incisions and preservation of anterior corneal biomechanical strength have been suggested as some of the advantages of SMILE over femtosecond laser-assisted LASIK (FS-LASIK). In this review, we compared previous published results of SMILE and FS-LASIK. The advantage, efficacy and safety of SMILE are compared with FS-LASIK. RECENT FINDINGS:SMILE achieved similar efficacy, predictability and safety as FS-LASIK. Greater preservations of corneal biomechanical strength and corneal nerves were observed in SMILE when compared with LASIK or PRK. Additionally, the incidence of postoperative dry eye syndrome was found to be less problematic in SMILE than in FS-LASIK. SUMMARY:SMILE is a promising new surgery for refractive error correction. Prospective and retrospective studies of SMILE have shown that results of SMILE are similar to FS-LASIK. With advances in femtosecond laser technology, SMILE may gain greater acceptance in the future. |
PMID: 26058022 [PubMed - indexed for MEDLINE] | |
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9. | Curr Opin Ophthalmol. 2015 Jul;26(4):243-8. doi: 10.1097/ICU.0000000000000173.
Advances in scleral lenses for refractive surgery complications.Author information:
AbstractPURPOSE OF REVIEW:The last two decades have brought advances in materials and manufacturing of large diameter rigid gas-permeable contact lenses, and a greater appreciation of the role of scleral lenses for therapeutic indications. The purpose of this review is to provide an update on the use of rigid gas-permeable scleral lenses in the management of patients with complications after refractive surgery. RECENT FINDINGS:There are recent reports on clinical experience with specific scleral lens designs from single institutions in cohorts that include patients who have undergone refractive surgery. Typically, these are patients with 'irregular corneas' after radial keratotomy or LASER assisted in-situ keratomileusis, but patients with keratectasia, dry eye syndrome, and corneal neuralgia are also reported. Visual outcomes and wearing success rates are high in these reports, although outcomes for refractive surgery patients are not reported separately. SUMMARY:Clinicians who encounter patients with complications after corneal refractive surgery should be aware of advances in scleral lenses. Scleral lenses are an alternative to surgical intervention in patients who might otherwise be considered poor contact lens candidates. |
PMID: 26058019 [PubMed - indexed for MEDLINE] | |
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10. | Autoimmun Rev. 2015 Aug;14(8):742-50. doi: 10.1016/j.autrev.2015.04.009. Epub 2015 Apr 24.
ANCA-associated vasculitis in patients with primary Sjögren's syndrome: detailed analysis of 7 new cases and systematic literature review.Guellec D1, Cornec-Le Gall E2, Groh M3, Hachulla E4, Karras A5, Charles P6, Dunogué B3, Abad S7, Alvarez F8, Gérard F1, Devauchelle-Pensec V9, Pers JO10, Puéchal X3, Guillevin L3, Saraux A9, Cornec D11; CRI (Club Rhumatismes et Inflammation) and the French Vasculitis Study Group.
Author information:
AbstractOBJECTIVES:To describe the clinical presentation, management and prognosis of patients diagnosed with both primary Sjögren's syndrome (pSS) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS:French nation-wide survey completed by a systematic literature review. RESULTS:This work identified 7 new cases of coexisting pSS and AAV: 2 microscopic polyangiitis (MPA), 2 granulomatosis with polyangiitis (GPA), 2 anti-myeloperoxidase (MPO)-ANCA renal-limited AAV, and 1 eosinophilic granulomatosis with polyangiitis (EGPA). The systematic literature search identified 15 previously published cases. Among the 22 patients, 19 were females. Mean age at diagnosis of AAV was 63.9±9.8years. All individuals with available information experienced at least one extra-glandular manifestation attributable to pSS. p-ANCA with anti-MPO specificity were found in 76.2% (16/21), c-ANCA with anti-PR3 specificity in 14.3% (3/21) and isolated c-ANCA in 13.6% (3/22). Vasculitis involved kidneys (n=13), lungs (n=8), skin (n=6), peripheral nerves (n=5), central nervous system (n=2), small bowel (n=1), muscle (n=1), ear chondritis (n=1) and sinuses (n=1). The mean AAV follow-up was 73.5 (±120.0) months. While on treatment, disease remission occurred in 77.3% of cases, and one death was reported in the first 6months after diagnosis. CONCLUSION:This work shows that AAV may occur in patients with pSS. These are most commonly p-ANCA associated vasculitis with anti-MPO specificity. AAV may reveal an underlying pSS or arise during its evolution, but did not precede pSS in any of these cases. AAV occurrence appears to be correlated with extra-glandular manifestations of pSS. Copyright © 2015 Elsevier B.V. All rights reserved. |
PMID: 25916811 [PubMed - indexed for MEDLINE] | |
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11. | Lupus. 2015 Jan;24(1):94-7. doi: 10.1177/0961203314554848. Epub 2014 Oct 8.
Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with systemic lupus erythematosus.Conti F1, Spinelli FR2, Colafrancesco S2, Truglia S2, Ceccarelli F2, Fattapposta F3, Sorice M4, Capozzi A4, Ferretti G5, Priori R2, Martinelli F2, Pirone C2, Alessandri C2, Valesini G2.
Author information:
AbstractCentral nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. |
PMID: 25297553 [PubMed - indexed for MEDLINE] | |
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