A two-stage filter for removing salt-and-pepper noise using noise detector based on characteristic difference parameter and adaptive directional mean filter.

In this paper, a two-stage filter for removing salt-and-pepper noise using noise detector based on characteristic difference parameter and adaptive directional mean filter is proposed. The first stage firstly detects the noise corrupted pixels by combining characteristic difference parameter and gray level extreme, then develops an improved adaptive median filter to firstly restore them. The second stage introduces a restoration scheme to further restore the noise corrupted pixels, which firstly divides them into two types and then applies different restoration skills for the pixels based on the classification result. One type of pixels is restored by the mean filter and the other type of pixels is restored by the proposed adaptive directional mean filter. The new filter firstly adaptively selects the optimal filtering window and direction template, then replaces the gray level of noise corrupted pixel by the mean value of pixels on the optimal template. Experimental results show that the proposed filter outperforms many existing main filters in terms of noise suppression and detail preservation.

AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, inhibits angiogenesis in models of ocular neovascular diseases.

PURPOSE: To determine whether systemic treatment with AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, inhibits neovascular processes in animal models of ocular disease. METHODS: AMG 386 was tested in a laser-induced choroidal neovascularization (CNV) model in monkeys using fluorescein angiography. The biodistribution of (125)I-AMG 386 was determined in cynomolgus monkeys by whole-body autoradiography and radioanalysis of ocular tissues. A murine retinopathy of prematurity (ROP) model was used to examine the effect of AMG 386 on established and newly formed retinal vessels, either as a single agent or when combined with VEGF inhibition.AMG 386 pharmacokinetics were evaluated in each model. RESULTS: In the CNV model, AMG 386 significantly decreased fluorescent angiographic leakage and reduced fibroplasia, indicating an impaired healing response consistent with angiogenesis blockade. Radiolabeled AMG 386 was widely distributed across ocular tissues, with highest concentrations in the choroid, cornea, retinal pigmented epithelium, iris/ciliary body, and sclera. In the ROP model, AMG 386 prevented pathologic retinal angiogenesis when administered from P8 to P16 but transiently impeded regression of these abnormal vessels when administered from P17 to P23. Combining AMG 386 with VEGF inhibition led to cooperative prevention of retinal angiogenesis in this model. No AMG 386-related ocular toxicities occurred, and no treatment-related clinical observations were made in any of the studies. CONCLUSIONS: In this study, AMG 386 inhibited angiogenesis in animal models of CNV and ROP, supporting investigation of AMG 386 for the treatment of ocular neovascular diseases in the clinical setting.

Specificity and selectivity evaluations of ligand binding assay of protein therapeutics against concomitant drugs and related endogenous proteins.

Macromolecule drugs designed against specific target proteins/ receptors have been applied in combination therapies, especially for complex and related diseases such as cancer for synergistic efficacy and alleviation of side effects. Protein therapeutics are typically measured using ligand binding assays (LBA). Evaluating the specificity and selectivity of LBA against their target proteins or in instances where concomitantly administered drugs are given was brought up during a conversation at the 3rd American Association of Pharmaceutical Scientists/US Food and Drug Administration Bioanalytical Workshop but was not discussed at the meeting sessions. The purpose of this article is to discuss the challenges related to this issue and present a few approaches and experiences to elicit further discussions. Specificity and selectivity tests should be based on the anticipated levels of the individual therapeutics with reference to the dosing regimens defined in the clinical study protocol. When the concomitantly administered compound is available as a pure or well-defined material, various concentrations from zero to above the expected high levels are added to validation samples of the protein therapeutics to assess specificity. Recovery results from spiked samples of target patient populations on concomitant medications can also be compared with those from normal individuals for selectivity. If the drug has an endogenous counterpart, the baseline concentrations of each lot should be subtracted from the test samples in the selectivity assessment. This article illustrates a flexible approach to evaluating specificity and selectivity on samples from target patient populations receiving multiple medications.