Paradoxical increase of visual impairment with punctal occlusion in a patient with mild dry eye

We report a paradoxical increase in visual impairment after punctal plug placement despite improvement in corneal epithelial damage caused by mild dry eye. Ocular higher-order aberrations (HOAs) were measured sequentially with a wavefront sensor before and after punctal plug insertion in a patient with mild dry eye. Although postblink HOAs tend to increase in normal subjects or patients with dry eye, after treatment there was a maximum spike in HOAs for a few seconds that decreased gradually. Excessive retention of tear film by punctal occlusion may cause inferosuperior asymmetrical distribution in precorneal tear-film thickness, possibly leading to slower wavefront on the inferior cornea and increased coma-like aberrations. Increased visual impairment might occur paradoxically despite improvement in the corneal epithelial damage caused by dry eye.     

Indocyanine green angiographic features of myopic subfoveal choroidal neovascularization as a prognostic factor after photodynamic therapy

PURPOSE: To determine the influence of clinical features and Indocyanine green (ICG) angiographic features on the visual outcome of patients with myopic sub-foveal choroidal neovascularization (CNV) who received photodynamic therapy (PDT). METHODS: Thirty-six consecutive patients (39 eyes) with myopic CNV who were followed up for more than one year after PDT were enrolled in this study. Clinical features included age, gender, refractive error, great linear dimension, and subretinal hemorrhage. ICG features included the lesion size, lacquer cracks, hypofluorescence surrounding the CNV (dark rim), peripapillary atrophy size, and visible prominent choroidal veins under the macula. Linear regression analysis was performed using the change in visual acuity (delta logMAR) as the dependent variable and the above factors as independent variables. RESULTS: At one-year follow-up after PDT, a younger age (p = 0.002) and the presence of a dark rim (p = 0.002) were significantly correlated with an improvement of visual acuity (decrement in logMAR) after PDT. Other factors had no significant influence on changes in visual acuity. CONCLUSIONS: Younger patients and patients with a dark rim on ICG angiography had a higher chance of visual improvement after PDT in myopic CNV.     

The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells

LB42708 (LB7) and LB42908 (LB9) are pyrrole-based orally active farnesyltransferase inhibitors (FTIs) that have similar structures. The in vitro potencies of these compounds against FTase and GGTase I are remarkably similar, and yet they display different activity in apoptosis induction and morphological reversion of ras-transformed rat intestinal epithelial (RIE) cells. Both FTIs induced cell death despite K-ras prenylation, implying the participation of Ras-independent mechanism(s). Growth inhibition by these two FTIs was accompanied by G1 and G2/M cell cycle arrests in H-ras and K-ras-transformed RIE cells, respectively. We identified three key markers, p21(CIP1/WAF1), RhoB and EGFR, that can explain the differences in the molecular mechanism of action between two FTIs. Only LB7 induced the upregulation of p21(CIP1/WAF1) and RhoB above the basal level that led to the cell cycle arrest and to distinct morphological alterations of ras-transformed RIE cells. Both FTIs successfully inhibited the ERK and activated JNK in RIE/K-ras cells. While the addition of conditioned medium from RIE/K-ras reversed the growth inhibition of ras-transformed RIE cells by LB9, it failed to overcome the growth inhibitory effect of LB7 in both H-ras- and K-ras-transformed RIE cells. We found that LB7, but not LB9, decreased the expression of EGFRs that confers the cellular unresponsiveness to EGFR ligands. These results suggest that LB7 causes the induction of p21(CIP1/WAF1) and RhoB and downregulation of EGFR that may serve as critical steps in the mechanism by which FTIs trigger irreversible inhibitions on the cell growth and apoptosis in ras-transformed cells.     

Medicinal plants as potential sources of lead compounds with anti-platelet and anti-coagulant activities

Medicinal plants are potential sources of lead compounds which can be further developed or optimised into novel therapeutics. This paper gives an overview of drug discovery from plants and an up-to-date and comprehensive review of plants and phytoconstituents reported to have anti-platelet and anti-coagulant activities.     

Correlation between cytoplasmic steroid receptors and tumour differentiation and invasion in endometrial carcinoma

The incidence and levels of cytoplasmic steroid receptors were studied in 155 endometrial carcinomas: oestrogen receptors (ER) were measured in all samples, progesterone receptors (PR) in 148 and androgen receptors (AR) in 118. Well-differentiated adenocarcinomas were significantly more likely to contain ER, PR and AR than were poorly-differentiated tumours, and mean values of ER and PR content were significantly higher in well-differentiated adenocarcinomas than in less-differentiated tumours. Receptor profiles in adenosquamous carcinomas and clear-cell carcinomas were similar to those in adenocarcinomas. Deeply invasive tumours were significantly less likely to be ER, PR or AR positive and, even when positive, such tumours had significantly lower mean levels of ER and PR. Poorly-differentiated tumours were significantly more likely to be ER-negative PR-positive than well-differentiated adenocarcinomas and adenosquamous carcinomas.