Several interactive and mutually perpetuating abnormal biochemical pathways, such as protein kinase C (PKC) activation, augmented polyol pathway, and non-enzymatic glycation, may be activated as a result of sustained hyperglycemia in diabetes. These abnormal pathways may in turn influence several vasoactive factors, which are probably instrumental in the production of functional and morphological changes in the retina in diabetes. The vasoactive factors such as endothelins, nitric oxide, vascular endothelial growth factors, etc., are of importance in mediating functional and structural alterations in early diabetic retinopathy. Intricate and interactive regulatory mechanism(s) among these factors may control ultimate availability of these molecules to produce biologically significant effects. A better understanding of these factors and their interactions would aid the development of adjuvant therapies for the treatment of diabetic retinopathy.

These results indicate an important contribution of both ET-1 and NHE-1 in the pathogenesis of diabetic cardiomyopathy. These data suggest that NHE-1 may act as a downstream mediator in the production of ET-induced functional and structural changes in the myocardium in diabetes.

Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.

Abstract:Corneal degenerative conditions such as keratoconus (KC) cause progressive damage to the anterior corneal tissue and eventually severely compromise visual acuity. The ability to visualize corneal tissue damage in-vivo at cellular or sub-cellular level at different stages of development of KC and other corneal diseases, can aid the early diagnostics as well as the development of more effective treatment approaches for various corneal pathologies, including keratoconus. Here, we present the optical design of an optical coherence tomography system that can achieve 0.95 µm axial resolution in biological tissue and provide test results for the system's spatial resolution and sensitivity. Corneal images acquired in-vivo with this system from healthy and keratoconic human subjects reveal the cellular and subcellular structure of the corneal epithelium, as well as the normal and abnormal structure of the Bowman's membrane and the anterior corneal stroma.

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Surgical staging of endometrial carcinoma includes the collection of peritoneal washings in the abdomen and pelvis. A positive finding upstages patients to International Federation of Gynecology and Obstetrics stage IIIA. However, the prognostic significance of such an upstaging, and thus the justification for the routine performance of this procedure, is unclear. This 5-year retrospective study was conducted to determine the frequency and prognostic significance of upstaging of endometrial carcinoma based solely on positive washings. The cohort for the study was collected by review of pathology reports of all washings that were performed prior to hysterectomies for suspected endometrial carcinomas over a 5-year period (01/1995-12/ 1999). Cases with positive cytology were selected if there was no grossly apparent intraperitoneal disease, no histologic evidence of extra-uterine tumor and the cases would otherwise have been considered stage I or II (case group). An age-matched control group was selected of stage I and II patients with the same histologic subtypes and negative washings (n ¼ 19). Of 220 endometrial carcinomas, peritoneal washing cytology was abnormal in 19 (8.6%) and was solely responsible for upstaging only 10 patients (4.5% of all cases, eightendometrioid, one-serous, one-mixed; nine stage IA or IB and one stage IIB). Adjuvant therapy was administered in 90% of the case group and 74% of the control group. After a median follow-up of 51 months (case group) and 63 months (control group), we found only a single patient with progression of disease (recurrence, metastases or death) in the control group. It is concluded that abnormal cytology without other evidence of extrauterine disease leads to upstaging of a minority of endometrial carcinoma patients (4.5%), but does not appear to affect their overall outcome. Although this is a small single site study, it raises questions about the value of this procedure in patients with endometrial cancer.

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