Jiri Uhlik

Structural changes in the bronchial mucosa of young children at risk of developing asthma

Bronchial asthma often starts in early childhood. Clinical manifestation of the disease is likely due to inflammatory processes in the airways initiated by various stimuli. Developed remodelling is regularly observed in the bronchial mucosa of adult asthmatics but we still lack information about its onset and latter development with the natural course of the disease. In this study, we analysed histological findings in bronchial biopsies obtained from very young children (under 4 yr of age). We hypothesized that initial undetectable changes in the airway epithelium of children predisposed to asthma may be one of the first mechanisms leading to morphological changes in the bronchial mucosa.

Intravitreal carboplatin concentration and area under concentration versus time curve after intravitreal and periocular delivery.

Purpose. To determine platinum (Pt) concentrations and area under the concentration versus time curve (AUC) of the vitreous humor after periocular or transcorneal intravitreal administration of carboplatin in rabbits. Methods. Eighteen albino rabbits were included in an in vivo experiment. Each animal received a single dose of either 30 mg of carboplatin by periocular injection (POI30 group: n=6) or 15 mg by periocular injection (POI15 group: n=6), or 0.05 mg by transcorneal intravitreal injection (TII group: n=6), respectively, into the right eye. Vitreous humor from the right eyes and plasma samples were collected post dose at 1, 2, 6, 24, 48, 168, and 336 hours or 448 hours, respectively. Flameless atomic absorption spectroscopy was employed to analyze total platinum concentrations in blood and vitreous humor. AUC was calculated using the trapezoidal rule. Results. Pt concentration was mostly <1 mg/L (0–3.15 mg/L) in the vitreous humor samples and ≥2 mg/L (2.33–7.3 mg/L) in the blood samples 1 hour after administration in POI groups. Markedly higher Pt concentrations were found 1 hour after intravitreal (TII) administration (10.285–66.759 mg/L) and decreased below 1 mg/L no less than 168 hours after administration. The mean AUC for Pt in vitreous humor was significantly lower (p=0.0001) after both POI30 and P0I15 administration compared to TII route (8.955 ± 2.464 mg/L/min). Conclusions. These findings proved that intravitreal carboplatin delivery enables the achievement of relatively stable concentrations and AUC of platinum in the rabbit vitreous humor. This moreover suggests that transcorneal intravitreal delivery of carboplatin aiming to treat retinoblastoma vitreous seeding is a promising mode of chemotherapy.

Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: Alternative retinoblastoma treatment

AIM To determine intravitreal and plasma concentrations and retinal toxicity after transcorneal intravitreal injection of 1 μg and 2 μg of topotecan (Hycamtin). METHOD Twelve healthy albino rabbits were included in this in vivo experiment. Six anesthetized albino rabbits received a single transcorneal intravitreal injection of 1 μg (group A) or 2 μg (group B) of topotecan. Vitreous and blood samples were collected until 168 h. Left eyes were treated with the same volume of saline. Plasma and vitreous levels of topotecan were determined by high-performance liquid chromatography. Area under the plasma concentration time curve (AUC) was calculated using trapezoidal rule. Clinical evidence of toxicity was classified into four grades according to anatomical structures. Electroretinograms (ERGs) were recorded. RESULTS Time to maximum concentration was observed up to 2 h after drug injection in group A whereas up to 1 h in group B. Low levels of topotecan were detected in plasma in both groups and in the vitreous humor of the contralateral eye in group B. Topotecan levels (mean vitreous AUC in group A 2.55 μg/mL.h and in group B 5.338 μg/mL.h) were detectable up to 6 h in both groups. We observed following structural changes in rabbit eyes: corneal vascularization, cataract, hemophthalmus, choroidal edema and focal retinal atrophy. Abnormal ERGs were obtained. CONCLUSION Our findings proved that transcorneal intravitreal administration of 1 μg and 2 μg of topotecan results in potentially cytotoxic intraocular concentrations. More studies are needed to establish the safety of topotecan for retinoblastoma in children.