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  • Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of experimental hepatic fibrosis. 17038628

    While CD8 subsets activate hepatic fibrosis, natural killer (NK) cells exhibit antifibrotic activity. Glatiramer acetate (GA) is an immune modulator for multiple sclerosis. We assessed the potential impact of GA on mouse hepatic fibrogenesis. Hepatic fibrosis was induced in C57BL/6 mice by intraperitoneal administration of carbon tetrachloride (CCl(4)) for 6 wk. During the last 2 wk, animals were also treated with either GA (200 mu/day ip) or medium and compared with naive and fibrotic mice (8 animals/group). GA markedly attenuated fibrosis without altering reactive oxygen species production. By morphometric measurement of Sirius red-stained tissue sections, the relative fibrosis area decreased from 5.28 +/- 0.32% (mean +/- SE) in the untreated CCl(4) group to 2.01 +/- 0.28% in CCl(4)+GA-treated animals, compared with 0.38 +/- 0.07% in naive mice. alpha-Smooth muscle actin immunoblotting and mRNA expression revealed a similar pattern. Serum aminotransferase and Ishak-Knodell necroinflammatory score were markedly elevated, to the same extent, in both CCl(4)-treated groups. Fibrosis induction was associated with significant increase in CD8 subsets and decrease in CD4 T cells. After GA treatment, however, NK content, CD4(+)CD25(+)FoxP3(+) cells, hepatic expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and apoptosis of hepatic stellate cells were all increased. Serum interleukin (IL)-10 levels markedly rose, whereas IL-4 fell. In vitro activation of human hepatic stellate cells cocultured with hepatitis C virus-derived peripheral blood lymphocytes decreased when lymphocytes were preincubated with GA before coculture. In an animal model of hepatic fibrosis, GA has an antifibrotic effect associated with decreased CD8 cells and reduced serum IL-4 levels and increased NK cells, CD4(+)CD25(+)FoxP3(+) cells, TRAIL, and elevated serum IL-10 levels.
    Dokumententyp:
    Referenz
    Produkbestellnummer:
    AB16942
    Produktbezeichnung:
    Anti-DR5 Antibody, CT

  • Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. 16100572

    Amyloid beta-peptide (Abeta) appears to play a key pathogenic role in Alzheimer disease (AD). Immune therapy in mouse models of AD via Abeta immunization or passive administration of Abeta antibodies markedly reduces Abeta levels and reverses behavioral impairment. However, a human trial of Abeta immunization led to meningoencephalitis in some patients and was discontinued. Here we show that nasal vaccination with a proteosome-based adjuvant that is well tolerated in humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat multiple sclerosis, potently decreases Abeta plaques in an AD mouse model. This effect did not require the presence of antibody, as it was observed in B cell-deficient (Ig mu-null) mice. Vaccinated animals developed activated microglia that colocalized with Abeta fibrils, and the extent of microglial activation correlated strongly with the decrease in Abeta fibrils. Activation of microglia and clearing of Abeta occurred with the adjuvant alone, although to a lesser degree. Our results identify a novel approach to immune therapy for AD that involves clearing of Abeta through the utilization of compounds that have been safely tested on or are currently in use in humans.
    Dokumententyp:
    Referenz
    Produkbestellnummer:
    AB5382
    Produktbezeichnung:
    Anti-Nitric Oxide Synthase II Antibody

  • The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells. 16457685

    Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells.
    Dokumententyp:
    Referenz
    Produkbestellnummer:
    06-680
    Produktbezeichnung:
    Anti-Androgen Receptor Antibody

  • Interaction between colonic acetate and propionate in humans. 2000822

    Animal studies suggest that propionate, derived from colonic carbohydrate fermentation, may be gluconeogenic and inhibit cholesterol synthesis in the liver. We therefore studied, in six healthy subjects, the effect of rectally infused solutions containing acetate alone (180 mmol), propionate alone (180 mmol), or a mixture of acetate (180 mmol) and propionate (60 mmol). Relative to the control infusion of normal saline, acetate increased serum cholesterol, glucagon, and acetate concentrations and reduced free fatty acids (FFAs) within 30 min. Propionate alone increased serum propionate, glucose, and glucagon with no effects on cholesterol and a delayed fall in FFAs. The addition of propionate to acetate resulted in no significant rise in serum cholesterol. These results are consistent with the hypothesis that colonic propionate is a gluconeogenic substrate in humans and inhibits the utilization of acetate for cholesterol synthesis.
    Dokumententyp:
    Referenz
    Produkbestellnummer:
    20-176
    Produktbezeichnung:
    100X GTPγS, 10mM

  • Nutritional status modulates behavioural and olfactory bulb Fos responses to isoamyl acetate or food odour in rats: roles of orexins and leptin. 19477242

    Food odours are major determinants for food choice, and their detection depends on nutritional status. The effects of different odour stimuli on both behavioural responses (locomotor activity and sniffing) and Fos induction in olfactory bulbs (OB) were studied in satiated or 48-h fasted rats. We focused on two odour stimuli: isoamyl acetate (ISO), as a neutral stimulus either unknown or familiar, and food pellet odour, that were presented to quiet rats during the light phase of the day. We found significant effects of nutritional status and odour stimulus on both behavioural and OB responses. The locomotor activity induced by odour stimuli was always more marked in fasted than in satiated rats, and food odour induced increased sniffing activity only in fasted rats. Fos expression was quantified in periglomerular, mitral and granular OB cell layers. As a new odour, ISO induced a significant increase in Fos expression in all OB layers, similar in fasted and satiated rats. Significant OB responses to familiar odours were only observed in fasted rats. Among the numerous peptides shown to vary after 48 h of fasting, we focused on orexins (for which immunoreactive fibres are present in the OB) and leptin, as a peripheral hormone linked to adiposity, and tested their effects of food odour. The administration of orexin A in satiated animals partially mimicked fasting, since food odour increased OB Fos responses, but did not induce sniffing. The treatment of fasted animals with either an orexin receptors antagonist (ACT-078573) or leptin significantly decreased both locomotor activity, time spent sniffing food odour and OB Fos induction in all cell layers, thus mimicking a satiated status. We conclude that orexins and leptin are some of the factors that can modify behavioural and OB Fos responses to a familiar food odour.
    Dokumententyp:
    Referenz
    Produkbestellnummer:
    AB3092
    Produktbezeichnung:
    Anti-Orexin-1 Receptor Antibody