Miltefosine and polyhexamethylene biguanide: a new drug combination for the treatment of Acanthamoeba keratitis.

BACKGROUND: In this study, a series of compounds - miltefosine, polyhexamethylene biguanide, chlorhexidine and propamidine isethionate - and combinations of the latter three agents with miltefosine were prepared and used in a rat model for the topical treatment of Acanthamoeba keratitis. METHODS: The corneas of rats were infected with Acanthamoeba hatchetti. On the fifth day, all corneas were microscopically examined in order to determine the grade of infections. Nine groups were then prepared: miltefosine (65.12 µg/mL); chlorhexidine (0.02%); polyhexamethylene biguanide (0.02%), propamidine isethionate (0.1%), miltefosine plus chlorhexidine, miltefosine plus polyhexamethylene biguanide; miltefosine plus propamidine isethionate; infected control; and a non-infected control group. The treatment was continued for 28 days. After the treatment, the corneas were excised and used for Acanthamoeba culture to investigate the presence of Acanthamoeba growth. For the determination of cytotoxicity of the drugs on L929 cells, colorimetric assays were performed. RESULTS: The best treatment results were obtained from the polyhexamethylene biguanide plus miltefosine group; the ratio of fully recovered eyes was 28.4%. It was proven that the miltefosine-polyhexamethylene biguanide combination yielded the highest anti-acanthamoebal activity in that approximately 86% of the eyes were cleared from amoebae. The cytotoxicity values of the miltefosine and the control groups were compared with other groups and found to be statistically different (P < 0.05). CONCLUSION: This in vivo study demonstrates that a miltefosine-polyhexamethylene biguanide combination is highly effective for the treatment of Acanthamoeba keratitis.

The Association between Diabetic Retinopathy and Levels of Ischemia-Modified Albumin, Total Thiol, Total Antioxidant Capacity, and Total Oxidative Stress in Serum and Aqueous Humor.

Purpose. To investigate the oxidant and antioxidant status of patients with type 2 diabetes mellitus and nonproliferative diabetic retinopathy (DRP). Methods. Forty-four patients who had cataract surgery were enrolled in the study. We included 22 patients with DRP in one group and 22 patients in the control group. Samples of aqueous humor and serum were taken from all patients. Serum and aqueous ischemia-modified albumin (IMA), total thiol, total antioxidant capacity (TAC), and total oxidative stress (TOS) levels were compared in two groups. Results. Median serum IMA levels were 44.80 absorbance units in the DRP group and 40.15 absorbance units in the control group (P = 0.031). Median serum total thiol levels in the DRP group were significantly less than those in the control group (3051.13 and 3910.12, resp., P = 0.004). Mean TOS levels in the serum were 2.93 ± 0.19 in the DRP group and 2.61 ± 0.26 in the control group (P = 0.039). The differences in mean total thiol, TAC, and TOS levels in the aqueous humor and mean TAC levels in the serum were not statistically significant. Conclusion. IMA, total thiol, and TOS levels in the serum might be useful markers in monitoring the risk of DRP development.

In vitro amoebicidal activity of propolis on Acanthamoeba castellanii.

PURPOSE: The aim of this study was to investigate the in vitro effects of an ethanolic extract of propolis on the growth and adherence of Acanthamoeba castellanii trophozoites and cysts. METHODS: The effect of propolis with concentrations of 8.0, 6.0, 5.0, 4.0, 3.0, and 2.0 mg/mL on the proliferation of A. castellanii trophozoites, and with a concentration of 62.25, 31.25, 15.62, 7.81, 3.90, 1.95, and 0.97 mg/mL on the proliferation of A. castellanii cysts, at 1, 3, 6, 12, 24, 48, and 72 h were examined in vitro. RESULTS: After 1-72 h, incubation in concentrations between 2.0 and 6.0 mg/mL, its effect was amoebistatic; at concentrations of 8.0 mg/mL and higher, its effect was amoebicidal. After 48 h or longer incubation times at 15.62 mg/mL and at higher concentrations, the propolis extract was cysticidal. At concentrations of 1.97 mg/mL or lower, there was no observable effect at any time point. CONCLUSIONS: These findings indicate that ethanolic extract of propolis has amoebicidal, as well as cysticidal, properties for Acanthamoeba trophozoites and cysts. Propolis alone, or in combination with other amoebicidal agents, may be used in clinical practice after further investigations.