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1.  Silibinin, Dexamethasone, and Doxycycline as Potential Therapeutic Agents for Treating Vesicant-Inflicted Ocular Injuries 
There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 µg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants.
doi:10.1016/j.taap.2012.07.014
PMCID: PMC3928638  PMID: 22841772
Nitrogen mustard; rabbit eye corneal culture; dexamethasone; doxycycline; silibinin; microbullae
2.  Congenital nasolacrimal duct cyst/dacryocystocele: An argument for a genetic basis 
Allergy & Rhinology  2012;3(1):e46-e49.
Embryogenesis of a congenital nasolacrimal duct (NLD) cyst is attributed to the failure of the Hasner membrane of the NLD system to cannulate. Prenatal diagnosis of congenital NLD cysts supports the argument for a developmental error, with a postnatal prevalence of 6%. The role of a genetic basis for this malformation has never been ascribed. We present a set of monozygotic twins with bilateral congenital NLD cysts as an argument for a genetic basis of this entity. A case report and literature review were performed. We present two cases of bilateral congenital NLD cysts occurring in a set of monozygotic twins. Patients were delivered at 37 weeks via cesarean section. The pregnancy was complicated by preterm labor at 33 weeks requiring administration of terbutaline and betamethasone. At presentation, twin A had bilateral eye discharge, erythema, and swelling medial to the medial canthi as well as nasal obstruction. Computed tomography (CT) showed classic bilateral cystic masses in the inferior meatus. The diagnosis of bilateral infected congenital dacryocystoceles was made. Twin B initially presented with only bilateral eye discharge and CT showed a dilated NLD system. Twin B subsequently developed early signs of bilateral dacryocystoceles the following day. Both patients underwent lacrimal probing and endoscopic marsupialization of the dacryocystoceles. Biopsies were consistent with dacryocystocele. Dacryocystocele is a common presentation of unresolved neonatal NLD obstruction. This case report in a set of identical twins is an argument for a genetic basis for the formation of this lesion.
doi:10.2500/ar.2012.3.0024
PMCID: PMC3404478  PMID: 22852130
Congenital; cyst; dacryocystocele; dacryocystorhinostomy; genetic; Hasner; nasolacrimal
3.  A Symptom Survey and Quality of Life Questionnaire for Nasolacrimal Duct Obstruction in Children 
Ophthalmology  2006;113(9):1675-1680.
Purpose
To develop and validate a new parental questionnaire addressing symptoms and health related quality of life (HRQL) in congenital nasolacrimal duct obstruction (NLDO).
Design
Cross-sectional study.
Participants
Children aged 6 to <48 months with and without clinical signs of NLDO.
Methods
A new questionnaire was developed using semi-structured interviews with parents of children with NLDO and through discussions with expert clinicians. Questionnaires were completed by parents of children with NLDO and without NLDO. Cronbach’s alpha was calculated as a measure of internal-consistency reliability. Factor analysis was used to evaluate a priori subscales; symptoms and HRQL. Discriminant construct validity was assessed by comparing questionnaire scores between children with and without NLDO and between affected and unaffected eyes of children with unilateral NLDO. Instrument responsiveness was determined by comparing pre- and post-surgical intervention scores in a subset of NLDO subjects who underwent surgical treatment.
Main outcome measure
NLDO questionnaire score.
Results
87 children were enrolled, 56 with NLDO and 31 without. All but two questions on the questionnaire showed a good distribution of responses, a high correlation with the rest of the questionnaire and excellent discrimination between patients with and without NLDO. Cronbach’s alpha values were good for the overall questionnaire (0.95), and for two predetermined subscales; symptoms (0.95) and HRQL (0.85). On a 0 to 4 scale, NLDO patients had worse scores compared to non-NLDO patients for both symptoms (mean difference = 2.1; 95% confidence interval (CI): 1.8 to 2.4) and HRQL (mean difference 1.2; 95% CI: 0.8 to 1.5) subscales. NLDO patients had worse scores pre-intervention compared to post-intervention for both the symptoms (mean difference = 2.2; 95% CI: 1.6 to 2.9) and HRQL (mean difference = 1.4; 95% CI: 0.8 to 2.1) subscales. Finally, NLDO patients had worse symptom scores for affected eyes compared to unaffected eyes (mean difference = 2.3; 95% CI: 1.9 to 2.6).
Conclusions
This novel NLDO questionnaire is useful in quantifying parental perception of symptoms and HRQL in childhood NLDO. The questionnaire may have a role in future clinical studies of NLDO
doi:10.1016/j.ophtha.2006.03.041
PMCID: PMC2440590  PMID: 16828516

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