Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress.

AIMS: We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress. METHODS AND RESULTS: NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed. CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet. CONCLUSION: Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.

Influence of the pupil size on visual quality and spherical aberration after implantation of the Tecnis 1-piece intraocular lens.

PURPOSE: To evaluate the influence of the pupil size on clinical results and objective parameters of optical quality of the Tecnis 1-piece (ZCB00) intraocular lens. SETTING: Centre of Ophthalmology, Eberhard-Karls University Tübingen, Germany. METHODS: In this study 51 eyes were implanted with a Tecnis 1-piece IOL. Best corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA) were assessed postoperatively. Total spherical aberration and corneal spherical aberration for optical zones of 3, 4, 5 and 6 mm were measured. Contrast sensitivity and depth of focus were evaluated with a 3 mm and 5 mm pinhole (PH). RESULTS: The mean follow-up time was 3.0 ± 0.4 months. Mean UCVA and BCVA were 20/25 ± 8 letters and 20/18 ± 4 letters, respectively. BCVA with both a 3 and a 5 mm PH was 20/18 ± 4 letters. The corneal spherical aberration was 0.02 ± 0.01, 0.06 ± 0.03, 0.14 ± 0.09 and 0.27 ± 0.22 for 3, 4, 5 and 6 mm optical zones. Mean total spherical aberration was -0.01 ± 0.02, 0.0 ± 0.03, 0.0 ± 0.06 and 0.0 ± 0.08 µm for 3, 4, 5 and 6 mm optical zones, respectively. Contrast sensitivity was not statistically significant different with a 5 mm or 3 mm PH. In addition, the defocus curves with a 3 mm and a 5 mm PH were not statistically significant different. CONCLUSION: The aspheric profile of the Tecnis 1-piece IOL reduces total spherical aberration to virtually zero at all pupil sizes from 3-6 mm. Thus, visual acuity, contrast sensitivity, refraction and defocus curve show the same good results at large pupil sizes compared with small pupil sizes.

Cleavage of E-cadherin: a mechanism for disruption of the intestinal epithelial barrier by Candida albicans.

To investigate how intestinal epithelial cells respond to contact with Candida albicans, an organism able to invade the bloodstream via the gastrointestinal tract, we focused on the junction proteins occludin, E-cadherin, and desmoglein-2. The levels of these 3 junction proteins were reduced in lysates of human intestinal epithelial monolayers (Caco-2) after a 24-h inoculation with C. albicans, compared with lysates from Saccharomyces cerevisiae-inoculated monolayers. Treatment with pepstatin A did not change the effect of C. albicans on full-length occludin, desmoglein-2, and E-cadherin; however, pepstatin A enhanced the accumulation of a 35-kDa fragment derived from the intracellular portion of E-cadherin. This 35-kDa fragment also accumulated in the presence of gamma-secretase inhibitors. These observations suggest that enhancement of E-cadherin cleavage by C. albicans generates an intracellular E-cadherin fragment that can serve as a substrate for gamma-secretase. An 89-kDa extracellular fragment of E-cadherin was detected in supernatants of C. albicans-inoculated monolayers; this cleavage event was insensitive to both pepstatin A and gamma-secretase inhibitors. Transepithelial electrical resistance, a measure of monolayer integrity, decreased significantly and synchronously with increased generation of the 89-kDa extracellular E-cadherin fragment. Cleavage of E-cadherin may destabilize the homotypic interactions between adjacent epithelial cells and could contribute to loss of monolayer integrity. These experiments identify 2 E-cadherin cleavage events that are enhanced by contact with C. albicans: an intracellular cleavage event that generates a substrate for gamma-secretase and an extracellular cleavage event that is temporally associated with an increase in monolayer permeability.