Human intraocular penetration pharmacokinetics of moxifloxacin 0.5% via topical and collagen shield routes of administration.

Purpose: To determine penetration of moxifloxacin 0.5% into human aqueous and vitreous via topical and collagen shield routes of administration.

Methods: Moxifloxacin 0.

Penetration pharmacokinetics of topically administered 0.5% moxifloxacin ophthalmic solution in human aqueous and vitreous.

Objective: To investigate the penetration of 0.5% moxifloxacin hydrochloride into the aqueous and vitreous after topical administration in humans.

Methods: A prospective, nonrandomized study of 20 patients scheduled for vitrectomy surgery between September 1 and December 31, 2003.

Stimulation of neovascularization by the anti-angiogenic factor PEDF.

Purpose: Examine the effect of (pigment epithelium-derived growth factor; PEDF) on laser-induced choroidal neovascularization (CNV).

Methods: Adult C57Bl/6 mice were anesthetized and four laser spots were placed in each quadrant of the fundus with a krypton red laser (614 nm, 50 microm, 0.05 second, 200 mW).

Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules: Deltayej Salmonella mutants induce superior CD8+ T-cell responses.

Salmonella-derived epitopes are presented on MHC molecules by antigen-presenting cells, and both CD4+ and CD8+ T cells participate in protective immunity to Salmonella. Therefore, mechanisms that allow Salmonella to escape specific immune recognition are likely to have evolved in this bacterial pathogen. To identify Salmonella genes, which potentially interfere with the MHC class I (MHC-I) presentation pathway, Tn10d transposon mutagenesis was performed.

Retrospective case series of juxtafoveal choroidal neovascularization treated with photodynamic therapy with verteporfin.

Purpose: To describe visual acuity and angiographic outcomes of juxtafoveal choroidal neovascularization (CNV) treated with photodynamic therapy and verteporfin (PDT).

Methods: Four hundred eighty-four consecutive eyes of 446 patients treated with PDT from January 1, 2001, to June 30, 2002, were identified from billing records. Fluorescein angiograms were reviewed retrospectively to identify juxtafoveal CNV.

Interleukin-6 and interleukin-10 are expressed in organs of normal young and old mice.

Interleukin-6 (IL-6) is a pleiotropic inflammatory cytokine, also endowed with inflammation-inhibiting properties. The status of interleukin-10 (IL-10) as an anti-inflammatory cytokine is more solidly established. The roles of IL-6 and IL-10 in the context of organ physiology, and their possible modulation by the aging process, are not satisfactorily understood.

The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription.

Although most cytokines are studied for biological effects after engagement of their specific cell surface membrane receptors, increasing evidence suggests that some function in the nucleus. In the present study, the precursor form of IL-1alpha was overexpressed in various cells and assessed for activity in the presence of saturating concentrations of IL-1 receptor antagonist to prevent receptor signaling. Initially diffusely present in the cytoplasm of resting cells, IL-1alpha translocated to the to nucleus after activation by endotoxin, a Toll-like receptor ligand.

Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness.

In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1alpha and IL-1beta), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1alpha (pIL-1alpha), mature IL-1beta (mIL-1beta), and mIL-1beta fused to a signal sequence (ssIL-1beta), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1alpha, which expresses IL-1alpha on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-gamma production.

Local delivery of IL-1 alpha polymeric microspheres for the immunotherapy of an experimental fibrosarcoma.

The immunotherapeutic effects of interleukin-1 alpha (IL-1 alpha) encapsulated within 1-5 microns-diameter poly (D, L-lactide) microspheres and delivered intratumorally into fibrosarcoma-bearing mice were investigated. Such microspheres are avidly taken up by macrophages, and directing IL-1 alpha into these cells may activate them to participate in antitumor responses in vivo. Treating of tumor-bearing mice with IL-1 alpha microspheres has increased their survival rate, as compared with control mice, untreated or treated with microspheres containing bovine serum albumin (BSA).

A continuous delivery system of IL-1 receptor antagonist reduces angiogenesis and inhibits tumor development.

The involvement of interleukin-1 (IL-1) in inflammation, tumor growth, and metastasis makes it an attractive target for therapeutic intervention. Here, we show that a continuous delivery of a low, but steady-state level of the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduced inflammatory responses and inhibited tumor development in mice, phenomena that are induced by IL-1, mainly secretable IL-1beta. The IL-1Ra was delivered from microencapsulated genetically engineered cells, which overexpress and secrete this mediator.

IL-1 is required for tumor invasiveness and angiogenesis.

Here, we describe that microenvironmental IL-1 beta and, to a lesser extent, IL-1 alpha are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1 beta knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1 beta KO mice.

Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of geographic atrophy from age-related macular degeneration.

Purpose: To report a case of presumed congenital hypertrophy of the retinal pigment epithelium in the fovea of an 88-year-old woman in the setting of geographic atrophy from age-related macular degeneration.

Design: Observational case report.

Methods: An 88-year-old woman was examined.

Interleukin-1--a major pleiotropic cytokine in tumor-host interactions.

Interleukin-1 (IL-1) represents a family of two agonistic proteins, IL-1alpha and IL-1beta, that are pleiotropic and affect hemopoiesis, inflammation, and immunity. In the context of the producing cell, IL-1beta is solely active in its secreted form, whereas IL-1alpha is active as an intracellular precursor, as a membrane-associated cytokine and to a lesser extent as a secreted molecule. IL-1 is abundant at tumor sites, where it may not only affect the growth and invasiveness of malignant cells, but where it may also induce antitumor immunity.

Different patterns of interleukin-1alpha and interleukin-1beta expression in organs of normal young and old mice.

The different physiological roles of interleukin-1alpha (IL-1alpha) and interleukin-1beta (IL-1beta) are not well understood, especially when considering the apparent overlap and redundancy of the two IL-1 molecules. Characterization of IL-1alpha and IL-1beta expression was performed in this study in organs from young and old mice, using immunohistochemistry and ELISA (enzyme-linked immunosorbent assay). The results indicate that organ IL-1alpha and IL-1beta display different patterns of expression: IL-1alpha is manifested more prominently in lymphoreticular organs (lungs, small intestine, spleen, liver), while IL-1beta is more evident in highly specialized and more vulnerable organs, which do not play a leading role in defense against infections and intoxication (heart, brain, skeletal muscle, kidney).

Angiostatin produced by certain primary uveal melanoma cell lines impedes the development of liver metastases.

Objectives: To evaluate the ability of human uveal melanomas to produce angiostatin in vitro and the effect of angiostatin on the development of liver metastases in vivo.

Methods: Human uveal melanoma cell lines (OCM1, OCM3, MEL202, MEL285, 92-1, OM431, and OMM1) were assayed for their ability to produce angiostatin in vitro by an angiostatin bioassay and by Western blot analysis. The OCM3 and OMM1 tumor cells were inoculated either in the posterior or the anterior segment of nude mice.

Etiology of blindness in an urban community hospital setting.

Objective: To determine the cause of monocular and binocular blindness in a predominantly nonwhite urban community hospital setting.

Design: Retrospective hospital-based cross-sectional study.

Participants: All 3562 unique subjects examined in the New and General Ophthalmology clinic at Parkland Memorial Hospital, Dallas, Texas, from July 1 to September 30, 1998.

Macrophage activation for the production of immunostimulatory cytokines by delivering interleukin 1 via biodegradable microspheres.

Interleukin 1alpha (IL-1alpha), a pleiotropic cytokine with multiple anti-tumour activities, has been investigated in our laboratory for its potential to serve as an immunotherapeutic agent. In the present study, an attempt was made to direct IL-1alpha to macrophages, in order to induce their immunoregulatory activities. For that purpose, IL-1alpha was encapsulated within biodegradable poly(lactic/glycolic acid) microspheres, 1-5 microm diameter in size.

Enhancing the immunogenicity of liposomal hepatitis B surface antigen (HBsAg) by controlling its delivery from polymeric microspheres.

Microencapsulated liposome systems (MELs) were investigated as a potential immunization carrier for a recombinant 22-nm hepatitis B surface antigen (HBsAg) particle. MELs were prepared by first entrapping the HBsAg particles within liposomes composed of phosphatidylcholine:cholesterol (1:1 molar ratio), which were then encapsulated within alginate-poly(L-lysine) (PLL) hydrogel microspheres. The entrapped HBsAg particles retained immunoreactivity, as judged by an enzyme-linked immunosorbent assay (ELISA).