Molecular Epidemiology of Adenoviral Keratoconjunctivitis in Korea.

Human adenoviruses (HAdVs) are a major cause of epidemic keratoconjunctivitis. We investigated the types of adenoviruses responsible for the recent epidemic of keratoconjunctivitis in Korea. From January to November 2019, 218 conjunctival swab samples were collected from patients clinically suspected as having adenoviral keratoconjunctivitis. Genotyping targeting of adenovirus capsid hexon genes was performed using PCR and sequencing. Of the 218 samples collected, 128 (58.7%) were positive for the adenovirus genes by PCR, and 126 samples were successfully genotyped. Adenovirus type 8 (HAdV-D8) was the most common type (67.5%), followed by HAdV-D64 (11.1%), HAdV-D37 (9.5%), HAdV-B3 (5.6%), HAdV-D53 (4.0%), HAdV-E4 (1.6%), and HAdV-D56 (0.8%). Adenoviral keratoconjunctivitis cases were the most frequent in July and August 2019, which were mainly caused by type 8. Phylogenetic analyses revealed little genetic distance among adenoviruses of the same type detected in our study. Our results provide basic data for further studies of adenoviral keratoconjunctivitis.

Exposure to Traffic-Related Particulate Matter 2.5 Triggers Th2-Dominant Ocular Immune Response in a Murine Model.

Ambient particulate matter (PM), a major component of air pollution, aggravates ocular discomfort and inflammation, similarly to dry eye disease (DED) or allergies. However, the mechanism(s) by which PM induces the ocular inflammatory response is unknown. This study investigated the immunological response of traffic-related fine particulate matter (PM2.5) on the ocular surface in a murine model. C57BL/6 mice were exposed by topical application to PM2.5 or vehicle for 14 days to induce experimental environmental ocular disease. Corneal fluorescein staining and the number of ocular inflammatory cells were assessed in both groups. The expression of IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and mucin 5AC (MUC5AC) in the ocular surface were evaluated by real-time PCR. An immunohistochemical assay evaluated apoptosis and goblet cell density. ELISA was used to determine the levels of serum IgE and cytokines of Type 1 helper (Th1) and Type 2 helper (Th2) cells after in vitro stimulation of T cells in the draining lymph nodes (LNs). Exposure to traffic-related PM2.5 significantly increased corneal fluorescein staining and cellular toxicity in the corneal epithelium compared with the vehicle control. A significant increase in the number of CD11b+ cells on the central cornea and mast cells in the conjunctiva was observed in the PM2.5 group. Exposure to PM2.5 was associated with a significant increase in the corneal or conjunctival expression of IL-1ß, IL-6, TNF, and MUC5AC compared to the vehicle, and increased maturation of dendric cells (DCs) (MHC-IIhighCD11c+) in draining LNs. In addition, PM2.5 exposure increased the level of serum IgE and Th2 cytokine production in draining LNs on day 14. In conclusion, exposure to traffic-related PM2.5 caused ocular surface damage and inflammation, which induced DC maturation and the Th2-cell-dominant allergic immune response in draining LNs.

Preclinical pharmacokinetics of PDE-310, a novel PDE4 inhibitor.

A novel phosphodiesterase-4 inhibitor, 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo[1,5-alpha] pyrimidine (PDE-310), has been synthesized for the treatment of respiratory diseases. We conducted in vitro and in vivo studies to characterize the pharmacokinetics of PDE-310. The high liver microsomal stability and low inhibitory potency against CYP isoforms of PDE-310 suggested a low first-pass effect and high bioavailability. PDE-310 exhibited high Caco-2 cell permeability in the absorptive direction (apparent permeability coefficients, ∼20 × 10(-6) cm/s), with higher transport in the secretory direction, giving efflux ratios of 3.9 and 2.6 at 5 and 10 µM, respectively. In addition, the high efflux ratio and improved absorption on treatment with efflux transporter inhibitors such as verapamil and MK-571 indicated the involvement of P-gp, BCRP and MRP2 in intestinal transport. PDE-310 bound strongly to human plasma proteins, whereas significantly more PDE-310 (27-34%) was free in rat plasma. Following intravenous administration, nonlinear elimination of PDE-310 was observed at the tested dose ranges (K(m), 0.87 µg/mL; V(max), 0.3 mg·h(-1)·kg(-1)). Following oral PDE-310 administration, dose-normalized AUC and T(max) increased significantly in a dose-dependent manner. PDE-310 exhibited high oral bioavailability (>70%) and was distributed well to various tissues except brain and testis.

Intravitreal bevacizumab for treatment of diabetic macular edema.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on visual function and retinal thickness in patients with diabetic macular edema (DME). METHODS: Thirty eyes of twenty-eight patients (mean age, 57.9+/-13.8 years) with DME were included in this study. Complete ophthalmic examination, including determination of best-corrected visual acuity (BCVA), stereoscopic biomicroscopy, and retinal thickness measurement by optical coherence tomography (OCT), was done at baseline and at each follow-up visit. All patients were treated with a 0.05 mL intravitreal injection containing 1.25 mg of bevacizumab. RESULTS: All patients completed 3 months of follow-up with a mean follow-up period of 5.26+/-2.39 months. The mean BCVA at baseline was 0.73+/-0.36 logMAR, which significantly improved to 0.63+/-0.41 (p=0.02), 0.58+/-0.36 (p=0.003), and 0.61+/-0.40 logMAR (p=0.006) at 1 week, 1 month, and 3 months. Final BCVA analysis demonstrated that 15 eyes (50%) remained stable and 12 (40%) improved >or=2 lines on BCVA. The mean central retinal thickness was 498.96+/-123.99 microm at baseline and decreased to 359.06+/-105.97 (p<0.001), 334.40+/-121.76 (p<0.001), 421.40+/-192.76 microm (p=0.035) at 1 week, 1 month, and 3 months. No ocular toxicity or adverse effects were observed. CONCLUSIONS: Intravitreal bevacizumab injection resulted in significant improvement in BCVA and central retinal thickness as early as 1 week after injection in patients with DME, and this beneficial effect persisted for up to 3 months. However, the slight reduction in this improvement at 3 months suggests that repeated bevacizumab injections might be necessary. To evaluate the long-term safety and efficacy, further prospective randomized controlled clinical trials will be needed.

Effects of smoking on the pharmacokinetics and pharmacodynamics of a nicotine patch.

The effect of smoking on the pharmacokinetics and pharmacodynamics of a nicotine transdermal delivery system, administered as a single dose or multiple doses, was examined in smokers (n=12) and nonsmokers (n=12). The study was a two-period, parallel trial. In the first period, a single dose of the Nicotinell TTS 20 patch was administered, followed by a 1-week washout period. Then, in the second period, multiple doses of the Nicotinell TTS 20 patch were administered over 4 days. Regarding the pharmacokinetics of nicotine, the AUC(36 h) and AUC(tau) of smokers were about 20% and 40% greater, respectively, than those of nonsmokers. Significant differences in heart rate were observed between smokers and nonsmokers at 10, 12, 16 and 24 h, and significant differences in systolic blood pressure were seen between smokers and nonsmokers at 12, 30 and 36 h in the single-dose study. With multiple doses, significant differences in systolic and diastolic blood pressures were detected between smokers and nonsmokers only at 72.5 and 82 h. Here, it is demonstrated for the first time that the pharmacokinetic and hemodynamic effects of a nicotine patch are significantly different between smokers and nonsmokers.