Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C

Purpose: To evaluate the potential of the vitamin E compound α-tocotrienol as antifibrotic agent in vitro. Methods: Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms α-tocopherol, α-tocopheryl acetate, α-tocopheryl succinate and α-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24h. Results: α-Tocopherol and α-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by α-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to α-tocopheryl succinate, 50μM or repeatedly 20μM of α-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400μg/ml showed a stronger antiproliferative effect than α-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. Conclusions: Of the vitamin E forms tested, only α-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of α-tocotrieno

Antifibrotic effects of tocotrienols on human Tenon's fibroblasts

Purpose: To compare the antifibrotic effect of vitamin E isoforms α-, γ-, and δ-tocotrienol on human Tenon's fibroblasts (hTf) to the antimetabolite mitomycin C. Methods: Antifibrotic effects of α- (40, 60, 80, 100, and 120μM), γ- (10, 20, 30, and 40μM) and δ-tocotrienol (10, 20, 30, and 40μM) on hTf cultures were evaluated by performing proliferation, migration and collagen synthesis assays. Whereas for vitamin E the exposure time was set to 7days to mimic subconjunctival application, cultures were exposed only 5 min to mitomycin C 100μg/ml to mimic intraoperative administration. Cell morphology (phase contrast microscopy) as an assessment for cytotoxicity and cell density by measuring DNA content in a fluorometric assay to determine proliferation inhibition was performed on day 0, 4, and 7. Migration ability and collagen synthesis of fibroblasts were measured. Results: All tested tocotrienol isoforms were able to significantly inhibit hTf proliferation in a dose-dependent manner (maximal inhibitory effect without relevant morphological changes at day 4 for α-tocotrienol 80μM with 36.7% and at day 7 for α-tocotrienol 80μM with 42.6% compared to control). Degenerative cell changes were observed in cultures with concentrations above 80μM for α- and above 30μM for γ- and δ-tocotrienol. The highest collagen synthesis inhibition has been found with 80 µM α-tocotrienol (62.4%) and no significant inhibition for mitomycin C (2.5%). Migration ability was significantly reduced in cultures exposed to 80 µM α- and 30 µM γ-tocotrienol (inhibition of 82.2% and 79.5%, respectively, compared to control) and also after mitomycin C treatment (60.0%). Complete growth inhibition without significant degenerative cell changes could only be achieved with mitomycin C. Conclusion: In vitro, all tested tocotrienol isoforms were able to inhibit proliferation, migration and collagen synthesis of human Tenon's fibroblasts and therefore may have the potential as an anti-scarring agent in filtrating glaucoma surger

Antifibrotic effects of tocotrienols on human Tenon's fibroblasts

Antifibrotic effects of α- (40, 60, 80, 100, and 120 μM), γ- (10, 20, 30, and 40 μM) and δ-tocotrienol (10, 20, 30, and 40 μM) on hTf cultures were evaluated by performing proliferation, migration and collagen synthesis assays. Whereas for vitamin E the exposure time was set to 7 days to mimic subconjunctival application, cultures were exposed only 5 min to mitomycin C 100 μg/ml to mimic intraoperative administration. Cell morphology (phase contrast microscopy) as an assessment for cytotoxicity and cell density by measuring DNA content in a fluorometric assay to determine proliferation inhibition was performed on day 0, 4, and 7. Migration ability and collagen synthesis of fibroblasts were measured. Results All tested tocotrienol isoforms were able to significantly inhibit hTf proliferation in a dose-dependent manner (maximal inhibitory effect without relevant morphological changes at day 4 for α-tocotrienol 80 μM with 36.7% and at day 7 for α-tocotrienol 80 μM with 42.6% compared to control). Degenerative cell changes were observed in cultures with concentrations above 80 μM for α- and above 30 μM for γ- and δ-tocotrienol. The highest collagen synthesis inhibition has been found with 80 µM α-tocotrienol (62.4%) and no significant inhibition for mitomycin C (2.5%). Migration ability was significantly reduced in cultures exposed to 80 µM α- and 30 µM γ-tocotrienol (inhibition of 82.2% and 79.5%, respectively, compared to control) and also after mitomycin C treatment (60.0%). Complete growth inhibition without significant degenerative cell changes could only be achieved with mitomycin C. Conclusion In vitro, all tested tocotrienol isoforms were able to inhibit proliferation, migration and collagen synthesis of human Tenon’s fibroblasts and therefore may have the potential as an anti-scarring agent in filtrating glaucoma surge

Dynamic contour tonometry in keratoconus and postkeratoplasty eyes

PURPOSE: To compare the performance of dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in measuring intraocular pressure in eyes with irregular corneas. METHODS: GAT and DCT measures were taken in 30 keratoconus and 29 postkeratoplasty eyes of 35 patients after pachymetry and corneal topography. Regression and correlation analyses were performed between both tonometry methods and between tonometry methods and corneal parameters. Bland-Altman plots were constructed. RESULTS: DCT values were significantly higher than GAT values in both study groups: +4.1 +/- 2.3 mm Hg (mean +/- SD) in keratoconus and +3.1 +/- 2.5 mm Hg after keratoplasty. In contrast to DCT, GAT values were significantly higher in postkeratoplasty eyes than in keratoconus. The correlation between the 2 tonometry methods was moderate in keratoconus (Kendall correlation coefficient, tau = 0.34) as well in postkeratoplasty eyes (tau = 0.66). The +/-1.96 SD span of the DCT-GAT differences showed a considerable range: -0.42 to +8.70 mm Hg in keratoconus and -1.87 to +7.98 mm Hg in postkeratoplasty eyes. In the keratoconus group, neither DCT nor GAT correlated significantly with any of the corneal parameters. In the postkeratoplasty group, both DCT and GAT measures showed a moderate positive correlation with corneal steepness, but only DCT had a significant negative correlation with the central corneal thickness (tau = -0.33). CONCLUSIONS: DCT measured significantly higher intraocular pressures than GAT in keratoconus and postkeratoplasty eyes. DCT and GAT measures varied considerably, and DCT was not less dependent on biomechanical properties of irregular corneas than GAT

Dietary tocopherol supplementation after trabeculectomy and phacotrabeculectomy: double-blind randomized placebo-controlled trial

The vitamin E compound alpha-tocopherol inhibits fibroblast growth in vitro. To evaluate its potential benefit in preventing failure of glaucoma filtration surgery, we prospectively investigated the outcome of filtering surgery with postoperative dietary alpha-tocopherol supplementation

Körperliche Aktivität und Leistungsfähigkeit in vier Schweizer Städten

As part of the Swiss National Research Program for the Prevention of Cardiovascular Disease, the degree of physical activity at work and during leisure time ws investigated in 3614 men and 4221 women living in four Swiss cities. Some 50% of the men and more than 60% of the women were considered insufficiently active. Since their jobs involve little physical activity, the quantity and quality of exercise needed for prevention of coronary heart disease can only be obtained from sports during leisure time. Of the men and women investigated in Aarau, 65 and 61% respectively volunteered for a bicycle ergometer test while in Nyon the participation in this part of the study was considerably lower (29 and 24% of the men and women). In both sexes and all age groups the mean values for the extrapolated maximum oxygen uptake were comparable to those reported from other highly industrialized countries

Novel pressure‐to‐cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value

Tocotrienol inhibits proliferation of human Tenon’s fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C

PURPOSETo evaluate the potential of the vitamin E compound alpha-tocotrienol as antifibrotic agent in vitro.METHODSUsing human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms alpha-tocopherol, alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5 min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24 h.RESULTSalpha-Tocopherol and alpha-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by alpha-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to alpha-tocopheryl succinate, 50 microM or repeatedly 20 microM of alpha-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400 microg/ml showed a stronger antiproliferative effect than alpha-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C.CONCLUSIONSOf the vitamin E forms tested, only alpha-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of alpha-tocotrienol

Failure of single-unit restorations on root filled posterior teeth: a systematic review.

This systematic review investigated the failure rate of conventional single-unit restorations in root filled posterior permanent teeth. Two reviewers independently applied eligibility criteria, extracted data and assessed the quality of the evidence of each included study according to the Cochrane Collaboration's procedures for randomized control trials (RCTs) and the STROBE criteria for observational studies. The MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Oral Health Group Trials Register and CENTRAL (via Cochrane Library) databases were searched electronically (January 1993 to week 1, February 2015). This was complemented by an additional hand search of selected journals and the references of relevant studies. Clinical studies published on root filled single-unit restorative treatments with a mean follow-up period of at least 3 years were selected. The outcome measured was clinical or radiological failure. Overall, the four RCTs and the single observational study included were of low and high quality, respectively. Therefore, a meta-analysis was not possible. The pooled mean failure rates were reported according to the type of treatment and remaining coronal tooth structure. The current evidence suggested that the failure rates of the treatments may depend on the amount of remaining tooth structure and type of treatment. Post-retained crowns were associated with the most favourable outcome in teeth with one to two remaining coronal tooth wall(s), whereas post-free crowns were superior when greater tooth structure was available. Restorations in teeth without ferrules had such a high rate of failure that other treatment options should be considered