Therapy of Subclinical Mastitis during Lactation.

This study tested the hypothesis that increasing the duration and/or frequency of antimicrobial treatment of subclinical mastitis would result in a higher bacteriological cure rate. Glands with a positive California mastitis test (CMT) from cows with an elevated somatic cell count (>500,000 cells/mL) that had an intramammary infection were randomly assigned at cow level to no treatment (Control; n = 80 glands), intramammary infusion of 200 mg cloxacillin sodium on three occasions at 48 h intervals (3 × 48 h; n = 273 glands), five occasions at 24 h intervals (5 × 24 h; n = 279 glands), or on five occasions at 48 h intervals (5 × 48 h; n = 72 glands). Glands were resampled at 21 (±3) and 28 (±3) days after initiation of treatment. The gland-level cure rate for any pathogen was 5/80 (6.2%), 139/173 (49.8%), 172/297 (61.6%) and 58/72 (80.6%) for Control, 3 × 48 h, 5 × 24 h and 5 × 48 h, respectively. The cure rate for major pathogens (defined as Staphylococcus aureus or Streptococcus spp.) was 4/52 (7.7%), 84/197 (42.6%), 96/183 (52.5%) and 36/48 (75%) for Control, 3 × 48 h, 5 × 24 h and 5 × 48 h, respectively. We conclude that treatment was superior to no treatment, and bacteriological cure rate was higher with the 5 × 24 h protocol than for the 3 × 48 h protocol and was higher with the 5 × 48 h than the 5 × 24 h protocol.

beta-Sitosterol, beta-Sitosterol Glucoside, and a Mixture of beta-Sitosterol and beta-Sitosterol Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice.

We hypothesized that the phytosterols beta-sitosterol (BSS), beta-sitosterol glucoside (BSSG), and Moducare (MC; BSS:BSSG = 99:1) could modulate the growth of estrogen-dependent human breast cancer cells in vitro and in vivo. The present study evaluated the estrogenic and antiestrogenic effects of BSS, BSSG, and MC (0.001 to 150 micromol/L) on the proliferation of Michigan Cancer Foundation 7 (MCF-7) cells in vitro. Both BSS (>1 micromol/L) and MC (>50 micromol/L) increased MCF-7 cell proliferation. Treatment with 150 micro mol/L of BSS and MC increased cell growth by 2.4 and 1.5 times, respectively, compared to the negative control (NC) group. However, BSSG had no effect at the concentrations tested. The effects of dietary BSS, BSSG, and MC on the growth of MCF-7 cells implanted in ovariectomized athymic mice were also evaluated. Estrogenic effects of the phytosterols were evaluated in the NC, BSS, BSSG, and MC treatment groups, and antiestrogenic effects were evaluated in the 17 beta-estradiol (E(2)), E(2) + BSS, E(2) + BSSG, and E(2) + MC treatment groups. Mice were treated with dietary BSS (9.8 g/kg AIN93G diet), BSSG (0.2 g/kg diet), or MC (10.0 g/kg diet) for 11 wk. Dietary BSS, BSSG, and MC did not stimulate MCF-7 tumor growth. However, dietary BSS, BSSG, and MC reduced E(2)-induced MCF-7 tumor growth by 38.9% (P < 0.05), 31.6% (P = 0.08), and 42.13% (P < 0.05), respectively. The dietary phytosterols lowered serum E(2) levels by 35.1, 30.2, and 36.5% in the E(2) + BSS, E(2) + BSSG, and E(2) + MC groups, respectively (P < 0.05), compared to that of the E(2) treatment group. Estrogen-responsive pS2 mRNA expression in tumors did not differ among groups, but expression of the antiapoptotic marker B-cell lymphoma/leukemia-2 (bcl-2) in tumors from the E(2) + MC group was downregulated, compared to that of the E(2) treatment group. In summary, BSS and MC stimulated MCF-7 cell growth in vitro. Although BSSG comprises only 1% of MC, BSSG made MC less estrogenic than BSS alone in vitro. However, dietary BSS and MC protected against E(2)-stimulated MCF-7 tumor growth and lowered circulating E(2) levels.

Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats.

Due to the estrogenic properties of soy-derived isoflavones, many postmenopausal women are using these compounds as a natural alternative to hormone replacement therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is important, because a majority of breast cancer cases occur in this age group. Chemical induction of mammary tumors in female rats has been used to determine that exposure of the mammary gland to soy isoflavones prior to tumor induction is protective against tumor formation. Here we investigate the effect of dietary genistein on mammary tumors that have already formed. The study was designed to determine the action of dietary genistein in a low endogenous estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary tumor development and were then placed into one of three treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ 750 p.p.m. genistein) and negative-control (OVX alone). Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either estrogen-dependent or estrogen-independent using immunohistochemistry to identify the presence of both estrogen receptor (ER) alpha and the progesterone receptor (PR). Genistein at 750 p.p.m. increased the weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared with the negative-control animals. Genistein treatment also resulted in a higher percentage of proliferative cells in tumors and increased uterine weights when compared with negative-control animals. Collectively, these effects are probably due to the estrogenic activity of genistein. Plasma genistein concentrations in animals fed the isoflavone-containing diet were at physiological levels relevant to human exposure. Estradiol concentrations in ovariectomized animals not receiving an estradiol supplement were similar to those observed in postmenopausal women. The data suggest that in an endogenous estrogen environment similar to that of a postmenopausal woman, dietary genistein can stimulate the growth of a mammary carcinogen MNU-induced estrogen-dependent mammary tumors.