Luteinizing hormone synthesis in cultured fetal human pituitary cells exposed to gonadotropin-releasing hormone.

To investigate whether GnRH regulates LH synthesis during human development, pituitary cells from second trimester fetuses were incubated with [35S]methionine ([35S]met) and [3H]glucosamine ([3H]gln) for 48 h with 0, 10(-9), and 10(-7) mol/L GnRH. Immunoassayable (i) LH was measured in media and cellular lysates, and dual label scintillation analysis was used to quantitate incorporation of radiolabeled precursors into cells, trichloroacetic acid-precipitable proteins, and immunoprecipitated LH subjected to electrophoresis. Exposure of cells to GnRH did not affect cellular uptake or incorporation of precursors into proteins, but specifically increased total (secreted plus cellular) LH synthesis. Both GnRH concentrations significantly increased iLH release and enhanced secreted and cellular [3H]gln-LH. The secretion of [35S] met-LH was stimulated only by 10(-7) mol/L GnRH. The proportion of newly synthesized LH that was secreted and the 3H/35S ratio of secreted and cellular LH were uninfluenced by GnRH. Although basal LH synthesis was not sex dependent, total iLH content and GnRH-stimulated LH translation were greater in cells from females than in those from males. Therefore, GnRH regulates LH synthesis by second trimester fetal human gonadotrophs without influencing the proportion of total radiolabeled LH that is secreted. The existence of a sex difference in total iLH content and GnRH-stimulated LH translation is consistent with the sexual dimorphism in pituitary LH content occurring during human development.     

Identification of a type II insulin-like growth factor receptor in fish embryos

To determine whether fish have an insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6-P) receptor similar to that of mammals, we have performed binding, cross-linking, and immunoprecipitation experiments with wheat-germ-agglutinin- and mannose 6-phosphate (M6-P)-affinity-purified receptor preparations from fish embryos. In both receptor preparations, IGF-II binding was specific, because labeled IGF-II could only be completely displaced by cold IGF-II but not by IGF-I or insulin. Labeled IGF-II bound to a protein with a molecular mass of approximately 250 kDa, which could be immunoprecipitated with an antibody against the rat IGF-II receptor. IGF-II stimulated tyrosine kinase activity in wheat germ agglutinin preparations and was more potent than insulin or IGF-I, but neither peptide stimulated tyrosine kinase activity in M6-P preparations. Two fish cell lines (CHSE-214 and EPC) were used to confirm the IGF-II binding data obtained in the receptor preparations, revealing the presence of highly specific IGF-II binding and the absence of insulin binding. Furthermore, a decrease of the IGF-I receptors on the cell surface did not alter IGF-II binding in EPC cells. In conclusion, we have detected the presence of IGF-II/M6-P receptors in fish embryos that are similar in structure and specificity for their ligand to those found in mammals.     

Tumor necrosis factor exerts dose-dependent effects on erythropoiesis and myelopoiesis in vivo

Recombinant human tumor necrosis factor alpha (TNF) administered i.v. to Lewis rats as a daily low dose for 1 week induces an erythroid hyperplasia of late normoblasts. Although the erythroid marrow compartment is hyperplastic, the morphology of the normoblasts is dysplastic and there is no accompanying increase in circulating red blood cells, suggesting a state of ineffective erythropoiesis. TNF administered on the same daily schedule as a high dose induces an erythroid hypoplasia of late normoblasts and a peripheral anemia with decreases in the hematocrit and hemoglobin. A tremendous myeloid hyperplasia is noted in rats treated with high-dose TNF, and the mechanism of the erythroid anemia may be in part due to the increase in neutrophils. In support of the hypothesis that the erythroid anemia may be partly myelophthisic in nature, a decrease in marrow lymphocytes was also noted. On the other hand, the dysplastic morphology of the late erythroid precursors in rats treated with low-dose TNF would also be consistent with a destructive effect of TNF on erythroid precursors as a mechanism of TNF-related anemia. In light of the in vitro inhibitory effects of TNF on erythropoiesis and myelopoiesis as reported by previous investigators, the erythroid and myeloid hyperplasia noted in vivo most likely represent indirect effects.     

Synthesis of heterometallic metal–organic frameworks and their performance as electrocatalyst for CO2 reduction

Herein we report the solventless synthesis and doping of the benchmark HKUST-1(Cu) as a facile route to afford heterometallic metal–organic frameworks (MOFs) having proficient behavior as electrocatalytic materials in the reduction of carbon dioxide. Zn(ii), Ru(iii) and Pd(ii) were selected as doping metals (M_D) with the aim of partially replacing the Cu(ii) atoms of the pristine structure to afford HKUST-1(Cu,M_D) type materials. Apart from the high yield and good crystallinity of the obtained materials, the extremely high reagent concentration that the reaction conditions imply makes it feasible to control dopant loading in all cases. Prepared samples were processed as electrodes and assembled in a continuous flow filter-press electrochemical cell. Faraday efficiency to methanol and ethanol at Ru(iii)-based electrodes resulted in activity as high as 47.2%, although the activity of the material decayed with time. The interplay of the dopant metal and copper(ii), and the long-term performance are also discussed.

The solventless synthesis of heterometallic metal–organic frameworks and their proficient behavior as electrocatalysts in the CO₂ reduction to alcohols is presented.     

Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy

Journal of Gastroenterology - Pancreatic adenocarcinoma is a lethal cancer with poor response to chemotherapy and immune checkpoint inhibitors. Recent studies suggest that epigenetic alterations...     

Beneficial effect of morphine on the threshold of electrical fibrillation of the ventricle. Experimental study

The action of 2-3 mg/kg of morphine on the threshold of electrical fibrillation of the ventricle (TVF) in anesthetized dogs has been studied. The basal TVF was 10.5 +/- 4.9 mA, increased to 20.2 +/- 7.7 mA (P 0.005) with the administration of this drug. Comparatively, the effect of morphine on the TVF is similar to that of propranolol and bretilium and more effective than procainamide. The mechanism by which it acts is not well known. Perhaps it is due to a homogenization of refractory periods in the ventricle as well as a possible morphine-catacholamine interaction. Morphine in dosis of 2-3 mg/kg could occupy a place among the antiarrhythmic drugs of choice with antifibrillatory action, with important usefulness in the field of anestesiology of cardiopaths.