Screening strategy for cardiovascular disease before transplantation.

<p>Screening strategy for cardiovascular disease before transplantation.</p

Analysis of factors associated with early cardiovascular events after kidney transplantation in univariate analysis.

<p>Immunosuppressive regimen: <b>LIR = Low immunological risk</b> = Immunosuppressive therapy, included a combination of anti-CD25 (Basiliximab) 20mg at day 0 and 4, steroids 500mg at day 0, 125mg at day 1 then rapidly tapered to 10mg per day, calcineurin inhibitors (cyclosporine or tacrolimus) and antimetabolites; <b>HIR = High immunological risk</b> (immunized patients) = immunosuppressive therapy included induction with thymoglobulin (1.5mg/kg/day for five days), steroids 500mg at day 0, 125mg at day 1 then rapidly tapered to 10mg per day, calcineurin inhibitors (cyclosporine or tacrolimus), antimetabolites, intravenous immunoglobulin (four courses of 2g/kg).</p><p>^aFor an increase of 5 units</p><p>^bFor an increase of 1 unit</p><p>^cFor an increase of 10 units</p><p>Analysis of factors associated with early cardiovascular events after kidney transplantation in univariate analysis.</p

Patients’ characteristics at inclusion.

<p>Patients’ characteristics at inclusion.</p

Pre-transplant cardiovascular evaluation and results.

<p>All renal transplant recipients underwent electrocardiography, echocardiography and non-invasive testing.</p><p>Pre-transplant cardiovascular evaluation and results.</p

High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

<div><p>Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.</p></div

Animal weight gain and prostate weight following milk diets.

<p>Animal weight gain between 3 weeks of age (i.e. at the beginning of the different diets) and sacrifice (A) and prostate weights at sacrifice (B) are reported for Pb-Prl and KIMAP mice in all diet groups. Animal weight gain is expressed in grams (g) while prostate weights are represented as the ratio between half prostate weight and mouse weight (g). Each dot represents one animal (n = 10 mice per group); horizontal lines represent the mean of the group. P values are represented <i>vs</i>. water control group (*), or <i>vs</i>. whole milk group (#).</p

Mouse models and diet protocols.

<p>(A) Representation of the two mouse models of prostate tumorigenesis used in this study. The Pb-Prl transgenic model shown on the left involves overexpression of rat prolactin under the control of the probasin promoter. The KIMAP model shown on the right involves the knock-in of SV40 large T antigen at the PSP94 locus. Respective protocols for milk diet administration (B) are shown below each model. For both, milk was introduced at 3 weeks of age and milk diets lasted for the indicated duration. Mice were sacrificed at the end of regimens.</p

Effect of milk diets on expression of tumor markers.

<p>Various tumor markers relevant to Pb-Prl (A) and KIMAP (B and C) models were assessed in DP following 27- or 15-week milk diets respectively, as compared to control (water) group. Proliferation index (Ki-67 staining, shown for both models), activated Stat5 (p-Stat5) and p63 expression (for Pb-Prl mice) and c-Fes expression (for KIMAP mice) were assessed from immunohistochemical (IHC) analysis (n = 6 per group; pictures show representative staining, scale stands for 50μm). For each marker (except c-Fes), IHC were quantified and the results are represented on adjacent bar histograms and are expressed as fold change <i>vs</i>. control (water) group. L, lumen of the glands. (C) q RT-PCR analysis of c-Fes, Ki-67 and Gprc6a mRNA expression in DP of KIMAP mice following 15-week milk diets. Results are expressed as fold change <i>vs</i>. control (water) group and are shown as means ± S.D. P values are represented <i>vs</i>. water control group (*). <i>nd</i>, for not determined.</p

Composition of diets.

<p>Composition of diets.</p

Effect of milk diets on prostate tumor histopathology.

<p>Histological analysis of dorsal prostate in Pb-Prl (A) and KIMAP mice (B) after respectively 27- or 15-week milk diets, as compared to control (water) group. For each model, images are representative of the group (n = 10 mice per group). Sections were stained with haematoxylin/eosin (HE) and for both models, upper pictures correspond to images x4.3 magnification (scale stands for 500μm) and lower pictures correspond to images with higher magnification, x28 (scale stands for 50μm). L, lumen of the glands.</p