The 24-hour intraocular pressure control by tafluprost/timolol fixed combination after switching from the concomitant use of tafluprost and timolol gel-forming solution, in patients with primary open-angle glaucoma.

OBJECTIVE: The aim of this study was to evaluate the 24-hour intraocular pressure (IOP)-control effect of the tafluprost/timolol fixed combination (TAF/TIM-FC) in patients with primary open-angle glaucoma after they switched from the concomitant use of tafluprost and timolol gel-forming solution. PATIENTS AND METHODS: Twenty patients with primary open-angle glaucoma (12 male and 8 female; mean ± SD age, 57.0±7.1 years) were included in this study. The patients were treated for 8 weeks with the concomitant administration of tafluprost and timolol gel-forming solution (evening dosing). At the end of this period, the patients underwent 24-hour IOP monitoring (measured at 21:00, 01:00, 05:00, 09:00, 13:00 and 17:00). IOP was measured with Goldmann applanation tonometer (GAT) and Icare PRO at sitting position at all timepoints and additionally, at supine position with Icare PRO tonometer at 01:00 and 05:00. The patients were then all switched to TAF/TIM-FC treatment (evening dosing). After 8 weeks, the 24-hour IOP monitoring was repeated. RESULTS: Nineteen patients completed the study. The mean 24-hour IOPs in the concomitant and TAF/TIM-FC phases were 13.8±2.7 vs 13.3±2.8 mmHg (P=0.0033) with the GAT in the sitting position and 13.96±2.56 vs 13.48±2.56 mmHg (P=0.0120) with the Icare PRO in habitual positions. In comparison with the concomitant phase, significantly lower IOP was observed for the TAF/TIM-FC phase at 21:00 and 01:00 with the GAT and at 01:00 with the Icare PRO. In addition, the maximum IOP and fluctuations in IOP in habitual positions were lower for the TAF/TIM-FC phase than for the concomitant phase. CONCLUSION: TAF/TIM-FC showed a stable 24-hour IOP-lowering effect and was equally or more effective than the concomitant use of tafluprost and timolol gel, both when sitting and when in habitual positions.

Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System.

Genetic testing of PKD1 and PKD2 is expected to play an increasingly important role in determining allelic influences in autosomal dominant polycystic kidney disease (ADPKD) in the near future. However, to date, genetic testing is not commonly employed because it is expensive, complicated because of genetic heterogeneity, and does not easily identify pathogenic variants. In this study, we developed a genetic testing system based on next-generation sequencing (NGS), long-range polymerase chain reaction, and a new software package. The new software package integrated seven databases and provided access to five cloud-based computing systems. The database integrated 241 polymorphic nonpathogenic variants detected in 140 healthy Japanese volunteers aged >35 years, who were confirmed by ultrasonography as having no cysts in either kidney. Using this system, we identified 60 novel and 30 known pathogenic mutations in 101 Japanese patients with ADPKD, with an overall detection rate of 89.1% (90/101) [95% confidence interval (CI), 83.0%-95.2%]. The sensitivity of the system increased to 93.1% (94/101) (95% CI, 88.1%-98.0%) when combined with multiplex ligation-dependent probe amplification analysis, making it sufficient for use in a clinical setting. In 82 (87.2%) of the patients, pathogenic mutations were detected in PKD1 (95% CI, 79.0%-92.5%), whereas in 12 (12.8%) patients pathogenic mutations were detected in PKD2 (95% CI, 7.5%-21.0%); this is consistent with previously reported findings. In addition, we were able to reconfirm our pathogenic mutation identification results using Sanger sequencing. In conclusion, we developed a high-sensitivity NGS-based system and successfully employed it to identify pathogenic mutations in PKD1 and PKD2 in Japanese patients with ADPKD.

Elimination of ketoprofen from the stratum corneum after topical administration with ketoprofen formulations in human subjects.

PURPOSE: To assess the drug concentrations and elimination rate of ketoprofen in the stratum corneum following topical administration of two different formulations in human subjects for reference in the risk management of photocontact dermatitis caused by topical ketoprofen. METHODS: Ketoprofen tape and gel were used as test formulations. The stratum corneum at the application sites was removed by tape-stripping at scheduled times after removal of the formulations. The ketoprofen concentration in the stratum corneum was determined by liquid chromatography with tandem mass spectrometry. RESULTS: The ketoprofen concentration in the stratum corneum decreased and the elimination half-life in the stratum corneum was comparable between tape and gel after removal of the test formulations. The ketoprofen concentration in the stratum corneum decreased more rapidly after the subjects took a shower. Ketoprofen was not detected in the stratum corneum adjacent to the tape application sites. CONCLUSIONS: Ketoprofen in the stratum corneum appears to reach the lower limit of quantitation (0.005 µg) 12-16 days after removal of tape or gel. This period is similar to that recommended for avoiding ultraviolet light after removal of topical ketoprofen formulations in the Summary of Product Characteristics for topical ketoprofen in the European Union.

Casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro improves central blood pressure and arterial stiffness in hypertensive subjects: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This trial evaluated the effects of casein hydrolysate containing milk-derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), on central blood pressure and arterial stiffness. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 70 Japanese subjects aged 50-69 years with untreated stage-I hypertension. They were randomly assigned to two groups, which received either placebo tablets or active tablets containing 3.4 mg of VPP and IPP. At the beginning and end of the 8-week intervention, hemodynamic parameters, including central blood pressure and brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, were measured. RESULTS: A significant difference in changes in central systolic blood pressure between the groups was observed (active: -11.0±11.0 vs placebo: -4.5±9.6 mmHg, P<0.01). In the active group, reductions in baPWV (-73.9±130.0 vs -8.4±137.1 cm/s, P<0.05), brachial SBP (-10.5±11.5 vs -3.9±9.6 mmHg, P<0.05), and radial mean blood pressure (-7.3±8.9 vs -2.0±7.4 mmHg, P<0.01) were significantly greater as compared with the placebo group. CONCLUSION: Casein hydrolysate containing VPP and IPP improves central SBP and baPWV in hypertensive subjects, which suggests VPP and IPP might have beneficial effects on arterial properties.