Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Fabrication and Characterization of Electrospun Folic Acid/Hybrid Fibers: In Vitro Controlled Release Study and Cytocompatibility Assays.

The fabrication of skin-care products with therapeutic properties has been significant for human health trends. In this study, we developed efficient hydrophilic composite nanofibers (NFs) loaded with the folic acid (FA) by electrospinning and electrospraying processes for tissue engineering or wound healing cosmetic applications. The morphological, chemical and thermal characteristics, in vitro release properties, and cytocompatibility of the resulting composite fibers with the same amount of folic acid were analyzed. The SEM micrographs indicate that the obtained nanofibers were in the nanometer range, with an average fiber diameter of 75-270 nm and a good porosity ratio (34-55%). The TGA curves show that FA inhibits the degradation of the polymer and acts as an antioxidant at high temperatures. More physical interaction between FA and matrices has been shown to occur in the electrospray process than in the electrospinning process. A UV-Vis in vitro study of FA-loaded electrospun fibers for 8 h in artificial acidic (pH 5.44) and alkaline (pH 8.04) sweat solutions exhibited a rapid release of FA-loaded electrospun fibers, showing the effect of polymer matrix-FA interactions and fabrication processes on their release from the nanofibers. PVA-CHi/FA webs have the highest release value, with 95.2% in alkaline media. In acidic media, the highest release (92%) occurred on the PVA-Gel-CHi/sFA sample, and this followed first-order and Korsmeyer-Peppas kinetic models. Further, the L929 cytocompatibility assay results pointed out that all NFs (with/without FA) generated had no cell toxicity; on the contrary, the FA in the fibers facilitates cell growth. Therefore, the nanofibers are a potential candidate material in skin-care and tissue engineering applications.

Intravitreal Infliximab Injection to Treat Experimental Endophthalmitis.

OBJECTIVE: The purpose of this study was to compare the use of an intravitreal injection of infliximab and of dexamethasone combined with vancomycin to treat experimental endophthalmitis induced by Staphylococcus epidermidis. MATERIALS AND METHODS: The study was conducted between March 25 and April 13, 2012. Twenty-five six-month-old healthy rabbits were used, each weighing 2.5-3 kg. The rabbits were randomized into five groups with five animals per group. Endophthalmitis was induced by 0.1 mL (103 colony-forming units) S. epidermidis in all groups. In group 1, injection was not implemented after the occurrence of endophthalmitis. In groups 2, 3, and 4, the following intravitreal injections were given 24 h after the occurrence of endophthalmitis: group 2, 0.1 mg/0.1 mL vancomycin; group 3, 1 mg/0.1 mL vancomycin and 1 mg/0.1 mL dexamethasone; and group 4, 1 mg/0.1 mL vancomycin and 2 mg/0.1 mL infliximab. Group 5 was the control/uninfected group. The rabbits were clinically assessed each day for seven days. On day 9, a histopathologic evaluation was performed after enucleation. RESULTS: After a clinical evaluation, no statistically significant difference was found between the vancomycin+infliximab and vancomycin+dexamethasone groups (p>0.05). The difference was significant when both groups were compared with the vancomycin group (p<0.001). After the histopathologic evaluation, no statistically significant difference was found among the three groups (p>0.05). CONCLUSION: An intravitreal injection of infliximab and of dexamethasone combined with vancomycin have similar clinical and histopathologic effects. To supplement the antibiotic treatment of endophthalmitis, infliximab in a safe dose range can be used as an alternative to dexamethasone to suppress inflammation and prevent ocular damage.

Phacoemulsification and Core Vitrectomy in Fuchs' Heterochromic Uveitis.

OBJECTIVE: To evaluate the efficacy of phacoemulsification combined with posterior capsulorhexis, core vitrectomy and ciliary sulcus intraocular lens (IOL) implantation in patients with Fuchs' heterochromic uveitis (FHU). MATERIALS AND METHODS: A total of 18 eyes of 18 patients with FHU underwent cataract surgery were included in the study. 18 eyes with FHU underwent posterior capsulorhexis, core vitrectomy and poly (methyl methacrylate) (PMMA) IOL implantation in the ciliary sulcus. Subjects were chosen for this procedure based on an intraoperative vitreous haziness assessment, performed by indirect ophthalmoscopy. Patients with +2 or more vitreous haziness qualified for this procedure. RESULTS: Of the 83 eyes with FHU that underwent cataract surgery, 18 eyes (21.6%) of 18 patients were employed in the study. There were 11 (61.1%) men and 7 (38.9%) women in the study; ages ranged from 23 to 47, with a mean of 32.06 years. Follow-up ranged from 8 months to 49 months. There were no intraoperative complications except for peripheral iris bleeding in 7 eyes. There was no severe intraocular inflammation in any patient postoperatively. All patients had 0.05 or better logMAR visual acuity after corneal suture removal. Glaucoma developed in 2 patients. For the short term period, the main vision threatening problem was suture-induced astigmatism. CONCLUSION: Cataract surgery combined with posterior capsulorhexis, core vitrectomy and IOL implantation in the ciliary sulcus is safe and leads to good visual outcome due to the removal of the hazy vitreous in patients with FHU.

Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration.

AIM: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA), and nitric oxide (NO), as well as activity of endothelial NO synthase (eNOS), in patients with age-related macular degeneration (AMD). METHODS: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30) were compared to a control group with no retinal pathology (n=30). RESULTS: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001), whereas NO levels and eNOS activity were higher in the control group (P<0.001). In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively. CONCLUSION: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD.

The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan.

PURPOSE: We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 µg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS: The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS: Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.

Orbital malign trichilemmal tumor with cerebral involvement.

Proliferating trichilemmal tumor is a rare encountered neoplasm. This neoplasm is usually benign, but it may be locally aggressive. To the best of our knowledge, magnetic resonance (MR) imaging features of cerebral involvement of this unusual neoplasm have not been described. We report the MR imaging findings of a case of malign proliferating trichilemmal tumor, with cerebral involvement.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy.

AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS: Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION: The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.