A Polyphenol-Rich Extract from Muscadine Grapes Prevents Hypertension-Induced Diastolic Dysfunction and Oxidative Stress.

Muscadine grapes are abundant in dietary polyphenols, but their effect on hypertension-induced cardiac damage is limited. This study assessed whether a muscadine grape skin/seed extract supplement (MGES) prevents hypertension-induced cardiac damage and oxidative stress. Male Sprague Dawley rats were treated for four weeks with drinking water, angiotensin II (Ang II) to induce hypertension, MGES, or both Ang II and MGES. Cardiac function assessed by echocardiography showed that Ang II increased systolic blood pressure while MGES alone or in combination with Ang II had no effect. Ang II increased E/e', an indicator of left ventricular filling pressure and diastolic dysfunction, by 41% compared to Control and co-treatment with MGES prevented the Ang II-mediated increase, suggesting that the extract attenuated hypertension-induced diastolic function. Ang II infusion increased urinary 8-hydroxy-2'-deoxyguanosine and cardiac 4-hydroxynonenal and malondialdehyde, which were prevented by the extract. The antioxidant enzymes catalase and superoxide dismutase 1 activity and mRNA were increased significantly in animals treated with MGES alone or in combination with Ang II, suggesting that the extract upregulates oxidative stress defense mechanisms in cardiac tissue. Thus, MGES may serve as a medical food to protect the heart from hypertension-induced diastolic dysfunction caused in part by excessive reactive oxygen species production.

InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph nodes during food borne infection of mice.

Intestinal Listeria monocytogenes infection is not efficient in mice and this has been attributed to a low affinity interaction between the bacterial surface protein InlA and E-cadherin on murine intestinal epithelial cells. Previous studies using either transgenic mice expressing human E-cadherin or mouse-adapted L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity for murine E-cadherin showed increased efficiency of intragastric infection. However, the large inocula used in these studies disseminated to the spleen and liver rapidly, resulting in a lethal systemic infection that made it difficult to define the natural course of intestinal infection. We describe here a novel mouse model of oral listeriosis that closely mimics all phases of human disease: (1) ingestion of contaminated food, (2) a distinct period of time during which L. monocytogenes colonize only the intestines, (3) varying degrees of systemic spread in susceptible vs. resistant mice, and (4) late stage spread to the brain. Using this natural feeding model, we showed that the type of food, the time of day when feeding occurred, and mouse gender each affected susceptibility to L. monocytogenes infection. Co-infection studies using L. monocytogenes strains that expressed either a high affinity ligand for E-cadherin (InlA(m)), a low affinity ligand (wild type InlA from Lm EGDe), or no InlA (ΔinlA) showed that InlA was not required to establish intestinal infection in mice. However, expression of InlA(m) significantly increased bacterial persistence in the underlying lamina propria and greatly enhanced dissemination to the mesenteric lymph nodes. Thus, these studies revealed a previously uncharacterized role for InlA in facilitating systemic spread via the lymphatic system after invasion of the gut mucosa.