Purpose To evaluate the efficacy and safety of topical 0.005% tacrolimus eye drop for treatment of refractory vernal keratoconjunctivitis (VKC). Methods This prospective study included 20 eyes of 10 patients with refractory VKC, who had active symptomatic disease despite conventional medications including topical steroids. After discontinuing all other medications, patients were treated with topical 0.005% tacrolimus eye drop four times a day. Changes in subjective symptoms and objective signs after treatment were evaluated, and development of possible complications was assessed. Results Mean age of patients was 21.3±7.4 years and mean duration of VKC was 12.1±5.8 years. After starting tacrolimus eye drop, patients were followed for a mean duration of 10.7 ± 3.7 months (range, 6-15 months). All symptoms including itching, redness, photosensitivity, foreign body sensation, and mucus discharge improved after the treatment; itching was the first symptom to show dramatic relief. In addition, there was improvement in objective signs including conjunctival hyperaemia, conjunctival papillary hypertrophy, giant papillae, limbal hypertrophy, corneal punctate epithelial erosions, and corneal pannus; conjunctival hyperaemia was the first sign to show improvement. No patient required addition of other medications including steroids for further relief. Any attempt to discontinue tacrolimus eye drop was associated with recurrence of patients' symptoms and signs, necessitating continued use of the medication during the entire follow-up time. No ocular complication related to tacrolimus was noted. Conclusion Topical 0.005% tacrolimus eye drop seemed to be a safe and effective treatment for steroid-resistant refractory VKC; however, long-term use was needed to control the disease.

Bevacizumab, an anti-VEGF antibody, has demonstrated trustworthy effects in treatment of retinal and choroidal neovascularization that both are crucial sight threatening conditions. However, the weak point is the short half-life of the drug in vitreous which necessitates frequent intravitreal injections. Accordingly employing controlled-release drug delivery systems such as polymeric nanoparticles (NPs) has been suggested. In this study albuminated-PLGA-NPs containing bevacizumab were prepared and studied intended for reducing the number of injections. NPs were formulated by double-emulsion method and a single dose of NPs was intravitreally injected to rabbits. The drug concentrations in vitreous and aqueous humor were assayed in different time intervals using ELISA and intraocular pharmacokinetic parameters were calculated. Moreover, coumarin-6 loaded albuminated-PLGA-NPs were employed to evaluate the distribution and persistence of the NPs in the posterior segment. Results revealed that the bevacizumab vitreous concentration maintained above 500 ng mL(-1) for about 8 weeks and 3.3 times elevation was observed in the drug vitreous MRT compared with the control. According to coumarin-6 NP tests, fluorescence emissions in posterior tissues were observed for 56 days which confirmed the nanoparticles persistence in ocular tissues during the test span. Therefore our prepared formulation may offer improvements in treatment of eye posterior segment neovascularization.

Purpose:To investigate the correlations between clinical findings and histopathologic changes in eyes with pterygium.Methods:This prospective study included 70 eyes with primary pterygia undergoing surgical excision. Prior to surgery, clinical features of the pterygia including extension over the cornea, redness, fleshiness (based on obscuration of the underlying episcleral vessels), and obliteration of the plica semilunaris were determined. Postoperatively, pterygium specimens were examined by hematoxylin-eosin and trichrome staining to evaluate histopathologic characteristics including vascular density, leukocytic infiltration, stromal elastosis, stromal fibrosis and subepithelial fibrosis. Correlations between clinical findings and histopathologic changes were then investigated.Results:There was a marginally significant correlation between the redness and the fleshiness of pterygium (P = 0.06). Both redness and fleshiness of the pterygium had significant positive correlation with dimensions of the lesion over the cornea. Moreover, larger pterygia were associated with obliteration of the plica semilunaris. Pterygium redness showed a significant correlation with vascular density (P = 0.04), and pterygium fleshiness had a significant correlation with stromal fibrosis (P = 0.04). Pterygium dimensions over the cornea demonstrated a positive correlation with vascular density and a negative correlation with stromal elastosis.Conclusion:Redness and fleshiness of pterygium were only marginally correlated with each other, and each one showed a correlation with different histopathologic features. Larger pterygia were associated with more significant changes at the clinical and histopathologic levels.

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Cisplatin (CP) nephrotoxicity is mainly due to reactive oxygen species. Oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on cisplatininduced acute renal failure was investigated in present study.Twenty-four rats were divided into four groups. The O 2 + CP and Air + CP groups were were subjected to i.p. injection of 5 mg/kg cisplatin, and in the Air + Saline and O 2 + Saline groups, saline was injected instead of cisplatin. O 2 + CP and O 2 + Saline groups were pretreated with oxygen (3h/d for two days), and the other two groups were pretreated with room air. Cisplatin was administered 24 h after last pretreatment session. Three days after cisplatin injection, plasma samples were obtained, and parts of kidney tissue were frozen for biochemical analysis or fixed in formalin for histological assessments. Preconditioning with oxygen prior to cisplatin administration led to reduced tubular necrosis and luminal cast formation and improvement of renal function, as was evidenced by significant reduction in plasma creatinine and urea levels. Oxygen pretreatment also significantly reversed cisplatin-induced reduction in renal catalase activity and glutathione level. It could be concluded that oxygen pretreatment could have a delayed protective effect against cisplatin nephrotoxicity, and that increased renal catalase activity may be involved in this protective effect of hyperoxia.

To accomplish an ideal wound healing process which promotes healthy tissue growth with less scaring, a novel gel based topical drug delivery system composed of 3 different polymers chitosan, dextran sulfate, and polyvinylpyrrolidone K30 (CDP) was prepared. The physicochemical properties of the prepared gels were investigated in vitro. Gels showed a maximum swelling ratio of 50 ± 1.95 times of dried gel in PBS at pH 7.4. The swelling ratios increase in acidic and alkaline pH to 55.3 ± 1.75 and 65.5 ± 2.42, respectively. In the rheological test, prepared gels revealed viscoelastic properties and a small linear viscoelastic region of 0.166%. In vivo wound healing promoting activities of CDP gels containing 20 μg/mL EGF were evaluated on surgically induced dermal wounds in rats using pathologic examination. The application of CDP gel with incorporated EGF significantly reduced the defect on the rat's skin and enhanced epithelial healing compared with the topical application of the EGF-free CDP gel. The results clearly substantiate the beneficial effects of the topical application of CDP containing EGF in the acceleration of healthy wound healing process with less scarring.

Efficacy of probiotics in the management of human inflammatory bowel disease (IBD) has been approved in the recent years. In the present work, the efficacy of a new biodegradable nanoparticles (NPs) of encapsulated and lyophilized probiotic extract (LPE) was examined in murine colitis. Colitis was induced by rectal instillation of trinitrobenzen sulfonic acid to male Wistar rats. The safety and effective dose of LPE was determined in a pilot study. To ease delivery into colon, LPE was encapsulated in chitosan-coated-poly (lactide co glycolide acid) NPs. After induction of colitis, animals in different groups received test compound in three doses by gavage for 10 days. Groups of sham, control (saline), and standard (dexamethasone) were also assigned. Colonic pathological examination, tumor necrosis factor alpha, interlukin (IL)-1β, myeloperoxidase (MPO), and lipid peroxidation (LPO) were performed. LPE at all doses (273, 545, and 1100 mg/kg) had positive effects in reduction of pro-inflammatory cytokines, LPO, and MPO in a dose-dependent manner. The formulated compound containing medium dose of LPE was more efficient in mitigating the experimental colitis in comparison with that of high-dose LPE. It is concluded that LPE and its nanoparticle-encapsulated form are very much effective in control of colitis. Regarding safety of this compound, further studies can be conducted in patients with IBD.

Chemical burns are a major cause of corneal haze and blindness. Corticosteroids are commonly used after corneal burns to attenuate the severity of the inflammation-related fibrosis. While research efforts have been aimed toward application of novel therapeutics. In the current study, a novel drug delivery system based nanostructured lipid carriers (NLCs) were designed to treat corneal alkaline burn injury. Rapamycin, a potent inhibitor of mammalian target of rapamycin pathway, was loaded in NLCs (rapa-NLCs), and the NLCs were characterized. Cell viability assay, cellular uptake of NLCs, and in vitro evaluation of the fibrotic/angiogenic genes suppression by rapa-NLCs were carried out on human isolated corneal fibroblasts. Immunohistochemistry (IHC) assays were also performed after treatment of murine model of corneal alkaline burn with rapa-NLCs. According to the results, rapamycin was efficiently loaded in NLCs. NLCs could enhance coumarin-6 fibroblast uptake by 1.5 times. Rapa-NLCs efficiently downregulated platelet-derived growth factor and transforming growth factor beta genes in vitro. Furthermore, proliferation of fibroblasts, a major cause of corneal haze after injury, reduced. IHC staining of treated cornea with alpha-smooth muscle actin and CD34 antibodies showed efficient prevention of myofibroblasts differentiation and angiogenesis, respectively. In conclusion, ocular delivery of rapamycin using NLCs after corneal injury may be considered as a promising antifibrotic/angiogenic treatment approach to preserve patient eyesight.