The present studies showed that sequential treatment with equine CG (eCG) and hCG not only induced an increase in ovarian weight, but also caused an estimated 4.6-fold increase in the number of ovarian surface epithelial cells. In addition, eCG-hCG treatment increased ovarian hepatocyte growth factor (HGF) messenger RNA levels. These studies also demonstrated that rat primary ovarian surface epithelial cells as well as a cell line derived from rat ovarian surface epithelium (i.e. ROSE-179 cells) do not express the LH (hCG) receptor. Both of these cells express c-Met, the receptor for HGF. To assess the effects of hCG and HGF on ovarian surface epithelial cell mitosis, ROSE-179 cells were cultured for 24 h in serum-supplemented medium on either glass or the synthetic fibronectin-like extracellular matrix protein, pronectin (RGD). The cells were then cultured for 24 h in serum-free medium in the presence or absence of hCG or HGF. The numbers of cells at 2, 24, and 48 h of culture were determined. The percentage of apoptotic cells was assessed by in situ DNA staining at 48 h of culture. In the serum-supplemented medium in the presence or absence of RGD, the number of ROSE-179 cells doubled. In serum-free medium, cell proliferation was reduced, and the percentage of apoptotic nuclei ranged between 10-15% regardless of the substrate. Neither mitosis nor apoptosis was influenced by hCG in the presence or absence of RGD. For ROSE-179 cells cultured in serum-free medium on RGD, HGF induced mitosis, resulting in a 2.8 +/- 0.2-fold increase in cell number compared with the 24 h control values. On a glass substrate in serum-free medium, HGF did not induce mitosis, but increased the percentage of apoptotic nuclei. Time-lapse photographic analysis revealed that on RGD, cells undergoing HGF-induced mitosis showed a transient reduction in cell contact. On glass, HGF caused many cells to completely lose contact and separate from each other. Collectively, these data suggest that in vivo gonadotropins stimulate HGF expression and ovarian surface epithelial cell proliferation. Based on in vitro studies, it is likely that the mitogenic action of hCG is mediated by HGF. However, HGF only induces mitosis in the presence of an extracellular matrix.

The present studies showed that sequential treatment with equine CG (eCG) and hCG not only induced an increase in ovarian weight, but also caused an estimated 4.6-fold increase in the number of ovarian surface epithelial cells. In addition, eCG-hCG treatment increased ovarian hepatocyte growth factor (HGF) messenger RNA levels. These studies also demonstrated that rat primary ovarian surface epithelial cells as well as a cell line derived from rat ovarian surface epithelium (i.e. ROSE-179 cells) do not express the LH (hCG) receptor. Both of these cells express c-Met, the receptor for HGF. To assess the effects of hCG and HGF on ovarian surface epithelial cell mitosis, ROSE-179 cells were cultured for 24 h in serum-supplemented medium on either glass or the synthetic fibronectin-like extracellular matrix protein, pronectin (RGD). The cells were then cultured for 24 h in serum-free medium in the presence or absence of hCG or HGF. The numbers of cells at 2, 24, and 48 h of culture were determined. The percentage of apoptotic cells was assessed by in situ DNA staining at 48 h of culture. In the serum-supplemented medium in the presence or absence of RGD, the number of ROSE-179 cells doubled. In serum-free medium, cell proliferation was reduced, and the percentage of apoptotic nuclei ranged between 10-15% regardless of the substrate. Neither mitosis nor apoptosis was influenced by hCG in the presence or absence of RGD. For ROSE-179 cells cultured in serum-free medium on RGD, HGF induced mitosis, resulting in a 2.8 +/- 0.2-fold increase in cell number compared with the 24 h control values. On a glass substrate in serum-free medium, HGF did not induce mitosis, but increased the percentage of apoptotic nuclei. Time-lapse photographic analysis revealed that on RGD, cells undergoing HGF-induced mitosis showed a transient reduction in cell contact. On glass, HGF caused many cells to completely lose contact and separate from each other. Collectively, these data suggest that in vivo gonadotropins stimulate HGF expression and ovarian surface epithelial cell proliferation. Based on in vitro studies, it is likely that the mitogenic action of hCG is mediated by HGF. However, HGF only induces mitosis in the presence of an extracellular matrix.

Background: Coronary microvascular dysfunction (CMD) is a common cause of angina and exercise intolerance in patients without obstructive coronary artery disease. The efficacy of ranolazine, a late sodium channel blocker, in patients with symptomatic obstructive coronary artery disease is well established. To evaluate the efficacy of ranolazine in CMD, we performed a systematic review and meta-analysis of randomized studies. Methods: MEDLINE, EMBASE, Cochrane CENTRAL, and conference abstracts were searched from January 1975 to March 2020. Randomized trials evaluating ranolazine in patients with CMD were CJC Open 3 (2021) 101e108

The present studies were designed to determine how disrupting cell contact induces rat ovarian surface epithelial cells (i.e., ROSE-179 cells) to undergo apoptosis. In the first series of studies, the effect of depleting serum and calcium on the levels of the adhesion proteins N-cadherin and beta-catenin was examined. These studies revealed that the depletion of serum and calcium results in the degradation of N-cadherin but not beta-catenin. However, the localization of beta-catenin changed from principally the plasma membrane to the nucleus. The nuclear localization of beta-catenin was demonstrated by Western blot and confocal microscopy. A second series of studies demonstrated that cells that lost contact in response to the depletion of serum and calcium showed enhanced beta-catenin-dependent transcription. Finally, forced expression of a stable form of beta-catenin resulted in an increase in beta-catenin within the cytoplasm of transfected ROSE-179 cells. When these beta-catenin transfected ROSE-179 cells were deprived of serum and calcium, beta-catenin accumulated within the nucleus and accelerated the rate at which these cells became apoptotic. These data indicate that in viable cells, beta-catenin is part of the adhesion complex that maintains cell contact. If calcium-dependent cell contacts are broken, beta-catenin accumulates within the nucleus, where it promotes transcription and ultimately the apoptotic death of ROSE-179 cells.

Objective: To compare the safety and efficacy of manual compression versus use of the MANTA® closure device for access management after Impella® removal on the intensive care unit (ICU).Background: The number of patients treated with percutaneous left ventricular assist devices (pLVAD), namely Impella® and ECMO, for complex cardiac procedures or shock, is growing. However, removal of pLVAD and large bore arteriotomy closure among such patients on the ICU remains challenging, since it is associated with a high risk for bleeding and vascular complications. Methods: Patients included in a prospective registry between 2017 and 2020 were analyzed. Bleeding and vascular access site complications were assessed and adjudicated according to VARC-2 criteria. Results: We analyzed a cohort of 87 consecutive patients, who underwent access closure after Impella® removal on ICU by using either the MANTA® device or manual compression. The cohort´s mean age was 66.1±10.7 years and 76 patients (87%) were recovering from CS. Mean support time was 40 hours (Interquartile range 24–69 hours). MANTA® was used in 31 patients (35.6%) and manual compression was applied in 56 patients (64.4%). Overall access related bleedings were significantly lower in the MANTA® group (6.5% versus 39.3%(odds ratio (OR) 0.10, 95% CI 0.01–0.50; p=0.001), and there was no significant difference in vascular complications between the two groups(p=0.55).Conclusions: Our data suggests that the application of the MANTA® device directly on the ICU is safe. In addition, it seems to reduce access related bleeding without increasing the risk of vascular complications.