1,721,079 research outputs found
Stereoselective oxidative cyclisations of 1,5,9-trienes : synthetic studies towards eurylene
No full textA novel synthetic route towards the stereoselective formation of trans-THF rings by permanganate promoted oxidative cyclisation of 1,5-diene precursors was developed. This methodology was applied to 1,5-dienoates and 1,5,9-trienoates to afford trans-THF regions of the natural products, (+)-linalool oxide and eurylene respectively. Synthesis of trans-THF aldehyde fragment 2.47 of eurylene was accomplished, using (+)-transcumylcyclohexanol as a chiral auxiliary to direct the stereoselective oxidative cyclisation of 1,5,9-triene 4.35 by permanganate. An efficient synthesis of cis-THF trial fragment 2.38 of eurylene was also achieved by permanganate mediated oxidative cyclisation of 1,5,9-triene 3.9, bearing (2S)-10,2camphorsultam as a chiral auxiliary. Trans-THF aldehyde 2.47 and cis-THF triol 2.38 intersect with a reported synthesis of eurylene, hence achieving a formal synthesis of the natural product. Seven, out of eight, stereogenic centres present in eurylene were established by two permanganate induced stereoselective oxidative cyclisations. Several coupling strategies were investigated to complete a total synthesis eurylene. Successful formation of the complete carbon skeleton 6.56 was achieved, although it was not possible to attain selective reduction of the triple bond in 6.56. The knowledge gained will be used to devise a revised end game, which ultimately a total synthesis to be achieved.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat
No full textIn the present study, turpentine oil was injected in the hind limb muscle of the rat to stimulate an acute-phase response (APR). The changes in the gene expression of cytokines and proteins known to be involved in the iron regulatory pathway were then studied in the liver and in extra-hepatic tissue. In addition to the strong upregulation of interleukin-6 (IL-6) and IL-1 beta observed in the inflamed muscle, an upregulation of the genes for IL1-beta and tumor necrosis factor-alpha, but not IL-6, were detectable in the liver. Hepatic Hepc gene expression increased to a maximum at 6 h after the onset of APR. An upregulation of transferrin, transferrin receptor 1 (TfR1), TfR2, ferritin-H, iron responsive element binding protein-1 (IRP1), IRP2 and divalent metal transporter gene expression was also found. Hemojuvelin (Hjv)-, ferroportin 1-, Dcytb-, hemochromatosisgene- and hephaestin gene expression was downregulated. Hepcidin (Hepc) gene expression was not only detectable in extra-hepatic tissues such as heart, small intestine, colon, spleen and kidney but it was also upregulated under acute-phase conditions, with the Hjv gene being regulated antagonistically. Fpn-1 gene expression was downregulated significantly in heart, colon and spleen. Most of the genes of the known proteins involved in iron metabolism are expressed not only in the liver but also in extra-hepatic tissues. Under acute-phase conditions, acute-phase cytokines (eg IL-6) may modulate the gene expression of such proteins not only in the liver but also in other organs
Cytokine-induced neutrophil chemoattractant-1 is released by the noninjured liver in a rat acute-phase model
No full textThe source of serum cytokine-induced neutrophil chemoattractant ( CINC-1) and consequences of its presence in the tissue of synthesis have not been clearly elucidated under acute-phase situation. To pursue this question, turpentine oil ( TO) was intramuscularly injected into rats, and RNA and local protein levels of acute-phase cytokines and of CINC-1 were studied in the TO injected gluteal muscle, as well as in noninjured muscle, in the liver, kidney, lung and spleen. The serum levels of acute-phase mediators and of CINC-1 were measured together with total leukocyte subpopulations. Recruitment of inflammatory cells in muscle and in the other organs was investigated by quantitative immunohistochemical methods. The effect of acute-phase mediators, including interferon gamma ( IFN-gamma) on the synthesis of CINC-1 in cultured hepatocytes was also investigated at the RNA and protein level. We found that the sera of the TO-treated rats contained elevated levels of IL-6, IL-1 beta and CINC-1. Increased serum levels of IFN-gamma were also observed not only in the injured muscle but also and to a higher extent in the liver. However, while neutrophils and mononuclear phagocytes were found in the injured muscle, no inflammatory cells were detected at the non-'inflamed' site, namely, the liver or in the other organs. In vitro, treatment of cultured hepatocytes with IL-1 beta led to elevated CINC-1 gene expression. This was true to a lesser extent upon IL-6 and tumor necrosis factor ( TNF-alpha) exposure. Interestingly, IFN-gamma did not effect CINC-1 gene expression. These results indicate that CINC-1 behaves as an acute-phase protein and its expression is inducible in hepatocytes. However, CINC-1-production in the liver does not lead to recruitment of inflammatory cells into the organ
Hepatic changes of erythropoietin gene expression in a rat model of acute-phase response
No full textAn acute-phase response is the systemic reaction of an organism to insult (e.g. infection, trauma and burning). It represents the 'first line' of defence of the body to tissue-damaging attacks. In the present work, we used a rat model of an intra-muscular turpentine oil (TO) injection to analyse erythropoietin (EPO) gene expression changes in the liver, one of the main target organs of acute-phase cytokines. EPO began to increase in the serum of TO-treated animals 6 h after injection and reached a maximum at 24 h (125 +/- 20 pg/ml). The detection of total RNA by polymerase chain reaction analysis showed that the levels of EPO gene expression in the liver were considerably increased between 2 and 12 h by up to 20-fold at the peak after TO administration, followed by a gradual decrease over the next 48 h, although the values remained significantly higher compared with the control group. In the kidney, after a sudden slight increase, the values declined progressively to 3.5-fold decrease at 12 h after the injection. In the liver, a parallel upregulation of the hypoxia-inducible factor-1 (HIF-1) alpha gene was observed (up to 4.7-fold increase), while HIF-2 alpha gene expression remained unaltered. On the other hand, the protein of both genes became detectable after the injection and increased progressively over 24 h, with a subsequent decline. These results suggest that EPO may be added to the increasing group of positive acute-phase proteins and the liver might represent the major source of the hormone under these conditions in the rat.DFG [SFB 402 TP: C6, D3, GRK 335
Comparison of Changes in the Gene Expression of Transferrin Receptor-1 and Other Iron Regulatory Proteins in the Rat Liver and Brain during Acute-Phase-Response.
No full textHepcidin and hemojuvelin gene expression in rat liver damage: In vivo and in vitro studies
No full textFERROPORTIN 1 IS A "NUCLEAR" NEGATIVE ACUTE-PHASE PROTEIN IN RAT LIVER: A COMPARISON WITH OTHER IRON-TRANSPORT PROTEINS
No full textComparison of Changes in the Gene Expression of Transferrin Receptor-1 and Other Iron Regulatory Proteins in the Rat Liver and Brain during Acute-Phase-Response.
No full textSTUDY OF EXPRESSION OF LOW MOLECULAR WEIGHT PROTEINS IN DIFFERENT AGE GROUPS OF LEUKEMIA PATIENTS
No full textFerritin L and ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions
No full textFerritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4 mu m thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus
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