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 (InlAm) 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 (InlAm), 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 InlAm 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.

Introduction: Most common benign breast conditions presenting in the breast clinics include fibroadenomas and mastalgia, both these conditions cause considerable anxiety in the patients. Among other treatment modalities, the hormonal drug treatments are gaining popularity. Ormeloxifene (centchroman) is an antiestrogenic drug which is shown to have effect in reducing the pain in mastalgia patients and the size of fibroadenoma. Objectives: Ormeloxifene is selective antiestrogen and a nonsteroidal drug. It has a discerning antiestrogen action and hence is useful for the treatment of mastalgia and multiple small fibroadenomas. Hence, the objective of our study was to assess the effect of Ormeloxifene (centchroman) on multiple fibroadenoma and mastalgia. Materials and Methods: Patients with benign breast disease attending our surgery outpatient department from June 2016 to July 2017. Patients were started on Ormeloxifene 30 mg on alternate days for a period of 3 months. Patients were followed up to 6 months after the inception of the study. Parameters recorded include the Visual Analog Scale (VAS) for pain and ultrasonography for breast lump size. Results: Thirty patients were included in the study. We found very good response in the mastalgia; the VAS scores in these patients dropped from 10 to 3 in 90% in the 1st week of introduction of the drug, and at the end of 1 month, almost all of the patients were painless. Overall final response was noted in terms of complete dissolution and change in the size was noted in 34% partial response in 46 %, no changes in 17 % and increase in size of fibroadenoma was noted in only one case. Conclusion: Novex is proved to be safe drug for the treatment of mastalgia and fibroadenoma. Its results were great in mastalgia group. At the end of 6 months, the number of surgeries (if needed) decrease and there is considerable improvement in the patient satisfaction rate.

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.

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Objectives Hypertension affects over a billion people world-wide and is a major risk factor for cardiovascular disease. Macrophages, the most abundant innate immune cells, home to the heart and secrete cytokines, inducing a heightened inflammatory response which results in fibrosis and cardiac damage. Muscadine grapes are rich in polyphenols, compounds with anti-proliferative, anti-fibrotic, and anti-inflammatory properties. Our aim was to determine whether a muscadine grape extract (MGE) rich in polyphenols prevents the macrophage inflammatory response induced by hypertension. Methods A proprietary extract was prepared from muscadine grape seeds and skins. Male Sprague-Dawley rats (8 weeks old) received drinking water (control), MGE at 0.2 mg total phenolics/mL, 24 μg/kg/h of angiotensin II (Ang II) via osmotic minipump to induce hypertension, or both Ang II and MGE (Ang II/MGE) for 4 weeks. Rats were pre-treated with MGE for 1 week prior to Ang II treatment. Blood pressure was measured weekly by tail cuff plethysmography. Tissues were collected and fixed for immunohistochemistry. Proliferation and migration of macrophage-like RAW264.7 cells were quantified in real-time. Results MGE had no effect on blood pressure in normotensive or hypertensive rats. MGE ameliorated Ang II-induced diastolic dysfunction (E/E’ ratio: 19.9 ± 0.8 control, 28.1 ± 1.1 Ang II, 22.3 ± 2.0 Ang II/MGE rats; n = 8; P < 0.05), interstitial cardiac fibrosis (P < 0.05) and collagen III deposition (0.9 ± 0.2% Control, 6.8 ± 1.0% Ang II, 2.8 ± 0.4% Ang II/MGE; P < 0.01). Thus, MGE may improve diastolic dysfunction in part through a reduction in pathological fibrosis. Ang II caused a significant increase in CD68-positive macrophages in cardiac tissue, which was blocked by MGE (% positive cells/field: control 6.1 ± 0.4, Ang II 12.5 ± 2.0, Ang II/MGE 5.4 ± 0.5, P < 0.01). Treatment of RAW264.6 cells with MGE (20 μg/mL total phenolics) for 18 h attenuated stimulated cell migration by 2-fold with no effect on proliferation (n = 3, P < 0.5), indicating that MGE may reduce the Ang II-mediated increase in cardiac macrophages by blocking migration. Conclusions MGE may serve as medical food to protect the heart from hypertension-induced inflammation thereby reducing cardiac fibrosis to improve diastolic dysfunction. Funding Sources Chronic Disease Research Fund.