Lifelong cytomegalovirus and early-LIFE irradiation synergistically potentiate age-related defects in response to vaccination and infection.

While whole-body irradiation (WBI) can induce some hallmarks of immune aging, (re)activation of persistent microbial infection also occurs following WBI and may contribute to immune effects of WBI over the lifespan. To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent murine cytomegalovirus (MCMV) and of early-life WBI over the course of the lifespan. In late life, we then measured the response to a West Nile virus (WNV) live attenuated vaccine, and lethal WNV challenge subsequent to vaccination.

Role of Cell-Intrinsic and Environmental Age-Related Changes in Altered Maintenance of Murine T Cells in Lymphoid Organs.

Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLNs) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment), we employed heterochronic parabiosis.

Acute systemic DNA damage in youth does not impair immune defense with aging.

Aging-related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age-related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole-body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells.

Application of interferon alpha 2b in conjunctival intraepithelial neoplasia: predictors and prognostic factors.

Purpose: To test the safety, tolerability, and efficacy of interferon alpha 2b for conjunctival intraepithelial neoplasia (CIN) and to evaluate the risk factors associated with its clinical outcome. A secondary goal is to identify predictors of duration of treatment to achieve good results.

Methods: A prospective, noncomparative case series.

[Hemodynamic component in glaucoma and its association with risk factors and cardiovascular disease].

Background And Objective: We sought to study the association of glaucoma with vascular disease, with 2 independent pathways: the association of glaucoma with cardiovascular disease (CVD) and the study of ocular hemodynamic variables (OHV) in glaucoma.

Material And Method: Cross-sectional study consisting of 73 patients: 25 without glaucoma, 28 primary open-angle glaucoma (POAG) and 20 normal-tension glaucoma (NTG). OHV, cardiovascular risk factors (CVRF) and CVD were determined.

"Oxygen with love" and diode laser treatment decreases comorbidity and avoidable blindness due to retinopathy of prematurity: results achieved in the past 12 years.

Aim: To determine whether the "Oxygen with Love" (OWL) and diode laser treatment provided in a neonatal intensive care unit has reduced the risk of avoidable blindness caused by retinopathy of prematurity (ROP) over the past decade.

Materials And Methods: A prospective observational cohort study was performed, in which 351 infants were examined for ROP. The inclusion conditions were as follows: preterm infants, birthweight <1500 g or <32 weeks' gestational age, and birth between 1 Jan 2000 to 31 August 2012.

Dietary putrescine reduces the intestinal anticarcinogenic activity of sulindac in a murine model of familial adenomatous polyposis.

The nonsteroidal antiinflammatory drug sulindac displays chemopreventive activity in patients with familial adenomatous polyposis (FAP). Sulindac metabolites induce apoptosis in colon tumor cells, in part, by a polyamine-dependent mechanism that can be suppressed with exogenous putrescine. To determine the relevance of this mechanism in animals, we treated Apc(Min/+) mice, a model of human FAP, with sulindac alone or in combination with dietary putrescine.

Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles.

Nos2 knockout mice were compared to wild-type mice for susceptibility to colitis in response to a diet supplemented with deoxycholate, a bile acid increased in the colon of individuals on a high-fat diet. Wild-type mice fed a fat-related diet, supplemented with 0.2% DOC, develop colonic inflammation associated with increases in nitrosative stress, proliferation, oxidative DNA/RNA damage, and angiogenesis, as well as altered expression of numerous genes.

Role of c-Myc in intestinal tumorigenesis of the ApcMin/+ mouse.

The c-MYC oncogene plays an important role in tumorigenesis and is commonly highly expressed in gastrointestinal cancers. In colon cells, c-MYC is regulated by the adenomatous polyposis coli (Apc) tumor suppressor gene. Multiple intestinal neoplasia (ApcMin/+ or Min) mice are heterozygous for a truncating Apc mutation and serve as a model of familial adenomatous polyposis (FAP) disease.

Role of polyamines in arginine-dependent colon carcinogenesis in Apc(Min) (/+) mice.

We evaluated the role of polyamines in arginine-dependent intestinal tumorigenesis in Apc(Min) (/+) mice. Arginine is a substrate for ornithine synthesis and thus can influence polyamine production. Supplementing the diet with arginine increased intestinal and colonic polyamine levels and colonic carcinogenesis.

Unique dietary-related mouse model of colitis.

Background: A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD.

The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis.

Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc-dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of Apc(Min/+) Nos2+/+ mice.