Different response to epidermal growth factor of hepatocytes in cultures isolated from male or female rat liver. Inhibitor effect of estrogen on binding and mitogenic effect of epidermal growth factor

Deoxyribonucleic acid (DNA) synthesis in hepatocytes isolated from the livers of male and female rats has been compared in monolayer culture. Plating efficiency, DNA and protein content, viability, and morphologic appearance were the same in cultures prepared with hepatocytes isolated from male or female rats. Epidermal growth factor (EGF)-induced DNA synthesis was significantly higher in hepatocytes from male rats than in hepatocytes from female rats. This was the case whether hepatocytes were isolated from normal or partially hepatectomized male or female rats. Hepatocytes isolated from regenerating liver synthesize more DNA than those isolated from normal liver in response to EGF. This increased response to EGF in hepatocytes derived from regenerating liver was relatively the same for male- and female-derived hepatocytes, but the magnitude of the response was considerably higher in male-derived hepatocytes. In contrast, in vivo DNA synthesis in the liver remnant after partial hepatectomy was similar in male and female rats if measured 24 h after the operation. A comparison of EGF binding to male- and female-derived hepatocytes maintained in primary culture indicated a lower number of high-affinity receptors for EGF in the female hepatocytes. The addition of estrogen to primary cultures of hepatocytes isolated from male rats inhibited EGF binding as well as EGF-induced DNA synthesis. Our studies show significant differences in DNA synthesis in response to EGF when male and female hepatocytes are compared in primary culture. The regenerative response after partial hepatectomy, on the other hand, was the same in male and female rats. Thus, our studies indicate that the sex of the donor rat is important when hepatocytes in culture are used for a variety of studies, such as hepatocyte metabolism, induction and control of DNA synthesis, and hepatocarcinogenesis. In addition, our results indicate that caution is advised when inferences are made from in vitro findings for in vivo conditions. © 1987

The effect of estrogen and tamoxifen on hepatocyte proliferation in Vivo and in Vitro

We have previously shown that changes in estrogen‐hepatocyte interaction occur during liver regeneration. Following 70% hepatectomy, estrogen levels in the blood were elevated, the number of estrogen receptors in the liver was increased and there was an active translocation of estrogen receptors from the cytosol to the nucleus. The injection of tamoxifen, an estrogen antagonist, inhibits hepatocyte proliferation following partial hepatectomy. The administration of 1 μg tamoxifen per gm body weight at zero time or 6 hr after the operation resulted in a significant inhibition both of DNA synthesis and of the number of cells in mitosis. Injections of tamoxifen 12 hr or later after the operation had no effect. Concomitant injections of equimolar amounts of estrogen abolished the inhibition by tamoxifen. The effects of estrogen and tamoxifen were also tested on hepatocytes in primary culture. Estrogens in the presence of 5% normal rat serum stimulated hepatocyte DNA synthesis as determined by [3H]thymidine incorporation and the labeling index, whereas epidermal growth factor‐induced DNA synthesis in the absence of normal rat serum was strongly inhibited. Tamoxifen, in contrast, inhibited DNA synthesis of hepatocytes in the presence of 5% normal rat serum and reversed the stimulatory effect of estrogen in the same system. Attempts to elucidate the mechanism of tamoxifen inhibition in vitro indicated that one effect of tamoxifen is to prevent the amiloride‐sensitive Na+ influx necessary to initiate hepatocyte proliferation. Copyright © 1989 American Association for the Study of Liver Disease

Fertilizer type influences tomato yield and soil N2O emissions

Improvements in crop management for a more sustainable agriculture are fundamental to reduce environmental impacts of cropland and to mitigate effects on global climate change. In this study three fertilization types – ammonium nitrate (control); mineral fertilizer added with a nitrification inhibitor (3,4-dimethylpyrazole phosphate (DMPP)), and an organo-mineral fertilizer (OM) – were tested on a tomato crop in order to evaluate effects both on crop production and soil N2O emissions. Plants grown under OM fertilization had a greater relative growth rate compared to mineral fertilization, due to a higher net assimilation rate, which was related to a greater light interception rather than to a higher photosynthetic efficiency. OM fertilization determined the highest fruit production and lower soil N2O fluxes compared to NH4NO3, although the lowest soil N2O fluxes were found in response to mineral fertilizer added with a nitrification inhibitor. It can be concluded that organo-mineral fertilizer is a better nutrient source compared to mineral fertilizers able to improve crop yield and to mitigate soil N2O emission

Circadian rhythm of hepatic cytosolic and nuclear estrogen receptors

The distribution of estrogen receptor between the cytosolic and nuclear compartments were evaluated in liver of male rats to determine whether a circadian rhythm exists. Cytosolic receptor reached a maximum level at 400 hours and a minimum at 2000 and 2400 hr. Nuclear receptor reached a maximum level at 800 hr and was lowest at 1600 and 2000 hr. Serum estradiol levels were also highest at 800 hr and lowest at 1600 hr. The variations in cytosolic and nuclear receptors are not reciprocal; in fact, the overall content of receptor in the liver is not constant and also displays a circadian rhythm. © 1986 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Electrical switching of a chiral lasing from polariton condensate in a Rashba-Dresselhaus regime

Efficient optical classical and quantum information processing imposes on light novel requirements: chirality with low threshold non-linearities. In this work we demonstrate a chiral lasing from an optical modes due to emerging photonic Rashba-Dresselhaus spin-orbit coupling (SOC). For this purpose we developed a new electrically tunable device based on an optical cavity filled with birefringent liquid crystal (LC) and perovskite crystals. Our novel method for the growth of single crystals of CsPbBr$_3$ inorganic perovskite in polymer templates allows us to reach a strong light-matter coupling regime between perovskite excitons and cavity modes, and induce polariton condensation. The sensitivity of the LC to external electric fields lets us to tune the condensate energy in situ and induce synthetic SOC. This shapes the condensate between a single linearly polarized or two circularly polarized separated in momentum, emitting coherent light. The difference in the condensation thresholds between the two SOC regimes can be used to switch on and off the chiral condensate emission with a voltage.Comment: 8 pages, 5 figure

The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first-line treatment of large B-cell lymphomas: a randomized trial by the Gruppo Italiano Studio Linfomi (GISL)

Background: It is still unclear the actual contribute of dose intensity (DI), dose size (DS) and dose density (DD) in the conventional chemotherapy of large, B-cell non-Hodgkin lymphomas. Methods: A prospective, randomized trial compared the cyclic schedule of ProMECE-CytaBOM chemotherapy (cyc-PC, 6 cycles) with a modified version of it, which administered the same drugs sequentially (seq-PC), with the same planned cumulative DI and an 83% DD, within the same time frame (113 days), but with three times higher DS of all the drugs except vincristine. Results: Fifty-six patients received cyc-PC and 52 seq-PC. The actual mean cumulative DI was 0.79 +/- 0.15 with cyc-PC, 0.78 +/- 0.17 with seq-PC. Response was complete in 59% and 52%, partial in 20% and 21%, null in 5% and 6%, respectively. There were four toxic deaths (two per arm). Relapses occurred in 36% and 37%, respectively. Toxicity was similar in both arms. Overall, failure-free, progression-free and disease-free survival (median follow-up: 54 months) were statistically indifferent. Conclusions: The very similar DI actually delivered in both arm seems to be the main common determinant of the indifferent results recorded. Increasing DS - at least within the limits clinically attainable without stem cell rescue - does not improve results