Intraocular Pressure Measurement by Rebound Tonometry (TonoVet) in Normal Pigeons (Columba livia).

We evaluated the applicability of a rebound tonometer (TonoVet) in pigeon eyes and established normal reference intraocular pressure (IOP) values in healthy pigeons; 20 eyes of euthanized pigeons were used for calibration of the TonoVet and 48 eyes of 24 adult pigeons were used for measurement of reference IOP. First, IOP of pigeon eyes ex vivo were measured using the 'd' and the 'p' modes of the TonoVet and compared to manometric IOP values from 5 to 80 mm Hg. Then, to establish normal reference values, IOP was measured from clinically normal pigeons in vivo. The 'd' and the 'p' modes of the TonoVet showed a strong linear correlation with the manometric IOP (R2 = .996 and .991, respectively). The obtained regression formulas were: y1 = 0.439x + 2.059 and y2 = 0.330x - 0.673, respectively (y1, 'd' mode of TonoVet; y2, 'p' mode of TonoVet; x, manometric IOP). The 'd' and the 'p' modes consistently measured one-half and one-third of the actual IOP, respectively. Therefore, the formula obtained through the 'd' mode was applied to obtain reference values. The calibrated IOP of normal pigeon eyes was 19.5 ± 4.4 mm Hg. The actual IOP could be calculated using the presented formula. Considering the limitations of the 'p' mode, use of the 'd' mode is more appropriate. Therefore, the TonoVet rebound tonometry under the 'd' mode is a reliable method for measuring IOP in pigeons.

Effects of prostaglandin-mediated and cholinergic-mediated miosis on morphology of the ciliary cleft region in dogs.

OBJECTIVE To compare morphology of the ciliary cleft (CC) region in dogs after topical administration of latanoprost, pilocarpine, or a combination of latanoprost and pilocarpine. ANIMALS 6 Beagles. PROCEDURES A prospective 4-phase crossover study with washout periods was performed. Latanoprost (phase L), pilocarpine (phase P), pilocarpine followed by latanoprost (phase PL), and latanoprost followed by pilocarpine (phase LP) were administered to the right eye. Artificial tears were administered to the left eye (control eye). For each phase, pupil diameter and intraocular pressure (IOP) were measured and ultrasonographic biomicroscopy was performed 2 hours after topical treatment. Angle opening distance (AOD), ciliary cleft width (CCW), ciliary cleft length (CCL), and ciliary cleft area (CCA) were evaluated. RESULTS All treated eyes had marked miosis without significant differences in pupil diameter among phases. Significant IOP reductions were detected for all phases, except phase P. The AOD and CCA were significantly increased in all phases for treated eyes, compared with results for control eyes. The CCW was significantly increased in phases P, PL, and LP; CCL was significantly increased in phases PL and LP. Comparison of treated eyes among phases revealed that CCW differed significantly between phases L and P and between phases L and PL. CONCLUSIONS AND CLINICAL RELEVANCE Prostaglandin-mediated and cholinergic-mediated miosis caused variations in CC configurations. When latanoprost and pilocarpine were used in combination, the first drug administered determined the cleft morphology, which was not fully reversed by the second drug. The CC morphology did not fully explain IOP reductions.

Comparison of corneal thickness measurements using ultrasound pachymetry, ultrasound biomicroscopy, and digital caliper in frozen canine corneas.

OBJECTIVE: To evaluate the clinical efficacy among ultrasound pachymetry (UP), ultrasound biomicroscopy (UBM), and manual measurement (MM) with digital caliper by comparing corneal thickness (COT) values obtained from frozen canine corneas ex vivo. PROCEDURES: COT was measured using UP, UBM, and MM in eight enucleated normal canine eyes frozen at -20 °C for 4 weeks. After thawing at room temperature for 2 h, the COT values were obtained from five sites on each cornea: central corneal thickness (CCOT), thickness at the 3, 6, 9, and 12 o'clock positions (3COT, 6COT, 9COT, and 12COT, respectively). For each device, measurements were performed three times at each designated site by one operator. Intraclass correlation coefficient, repeated-measures analysis of variance, and Bland-Altman plot were performed for statistical analyses. RESULTS: The mean CCOT was 839.0 ± 138.2, 857.6 ± 127.9, and 849.1 ± 132.8 µm for UP, UBM, and MM, respectively. There was no statistically significant difference among the measurements by all three devices (P > 0.05). The statistical agreement among these devices was also shown to be good according to Bland-Altman plots. In addition, the values measured on the peripheral sites of the cornea (3COT, 6COT, 9COT, and 12COT) also revealed no significant differences among the three devices. The difference between CCOT and peripheral corneal thickness was also statistically insignificant. CONCLUSIONS: The UP, UBM, and MM measurements showed statistically similar COT values. The UBM and UP provided accurate and reliable measurements comparable to MM and could be used effectively for clinical COT measurements.

Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA.

Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2) and tropomyosin-related kinase A (TRKA) via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

Ultrasound biomicroscopy and tonometry in ophthalmologically normal pigeon eyes.

OBJECTIVE: To evaluate the feasibility of ultrasound biomicroscopy (UBM) and tonometry in pigeons and to provide biometric reference ranges for normal pigeon eyes. ANIMALS STUDIED: Ten pigeons (Columba livia var. domestica) with ophthalmologically normal eyes. PROCEDURES: Ophthalmic examinations, including slit-lamp biomicroscopy and tonometry, were performed to confirm that the eyes were normal. UBM was then performed on the left eye. On each obtained image, the ciliary cleft (CC) length, CC width, and CC area, and iridocorneal angle (ICA) were measured. RESULTS: Richly vascularized iris was observed in all pigeon eyes. Mean intraocular pressure was 11.7 ± 1.6 mmHg, without any statistical difference between the left and right eyes. The UBM scanning procedure was well tolerated in all pigeons. Mean values of CC length, CC width, CC area, and ICA were 1.55 ± 0.17 mm, 0.36 ± 0.05 mm, 0.39 ± 0.04 mm2 , and 15.17 ± 1.06°, respectively. CONCLUSIONS: Ultrasound biomicroscopy could be a useful diagnostic tool to evaluate anterior ocular segment of pigeons.

Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK.

Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB), also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK), which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer. A cell viability assay revealed that pharmacological suppression of AKT using LY294002 enhanced the anti-cancer effect of fascaplysin in various cancer cells. Similarly, fascaplysin was observed to have improved anti-cancer effects in combination with compound C, a selective AMPK inhibitor. Another challenge showed that fascaplysin increased the efficacy of methotrexate (MTX)-mediated cancer therapy by suppressing genes related to folate and purine metabolism. Overall, these results suggest that fascaplysin may be useful for improving the anti-cancer efficacy of targeted anti-cancer drugs, such as inhibitors of phosphoinositide 3-kinase AKT signaling, and chemotherapeutic agents, such as MTX.

Influence of Size and Volume of Periapical Lesions on the Outcome of Endodontic Microsurgery: 3-Dimensional Analysis Using Cone-beam Computed Tomography.

INTRODUCTION: The purpose of this study was to examine the size, volume, and other parameters of preoperative periapical lesions measured from cone-beam computed tomographic (CBCT) images as potential prognostic factors in endodontic microsurgery. METHODS: A clinical database was searched for patients who had received endodontic microsurgery with preoperative CBCT examination between March 2010 and December 2014. The CBCT images were analyzed with the OnDemand3D software program (Cybermed, Seoul, South Korea). The mesiodistal (Lx), apicocoronal (Ly), and buccolingual (Lz) diameter and the volume (V) of the periapical lesions, destruction of the cortical bone, and height of the buccal bone plate (Lb) were measured independently by 2 examiners. The outcome was classified as a success or failure based on the clinical and radiographic evaluation at least 1 year after the operation. Univariate analyses using the chi-square or Fisher exact test were performed to show the correlation of the outcomes with variables to identify the potential predisposing factors. Multivariate analysis using a logistic regression model was performed with the associated variables. RESULTS: Ninety-five cases were evaluated after a period of at least 1 year, and 2 were extracted before the 1-year follow-up. The interexaminer agreements were excellent for the linear and volume measurement of the preoperative periapical lesion. A lesion volume above 50 mm(3) was found to be a significant negative predictor in the univariate analysis (P = .028) and the logistic regression model (P = .038). CONCLUSIONS: Within the limitations of this study, the volume of the preoperative periapical lesion had a significant effect on the outcome of endodontic microsurgery. It is suggested that further studies on endodontic microsurgery should be performed and that quantitative measurements using CBCT imaging may be useful for the analyses.

Comparison of clinical outcomes of endodontic microsurgery: 1 year versus long-term follow-up.

INTRODUCTION: The purpose of this study was to examine and compare the clinical outcome of endodontic microsurgery after 1 year of follow-up and over a period of 4 years. METHODS: The database of the Department of Conservative Dentistry, Yonsei University, Seoul, South Korea, was searched for patients who had undergone endodontic microsurgery and had been evaluated 1 year after surgery and over a period of 4 years. Two examiners independently evaluated the postoperative radiographs taken 1 year after surgery and over a period of 4 years using Rud's criteria. To analyze and compare the success rate based on the observation period, the McNemar test was performed with a significance level of 0.05. RESULTS: The study included 115 cases. Using Rud's criteria, the overall success rate of cases with 4 or more years of follow-up was 87.8% compared with 91.3% at 1 year of follow-up. There was no significant difference between the follow-up periods (P = .344). CONCLUSIONS: There was no significant difference in the clinical outcome after endodontic microsurgery when comparing 1-year follow-up periods with longer follow-up periods.