Search results for "Protein"
showing 10 items of 21431 documents
Bafetinib inhibits functional responses of human eosinophils in vitro
2012
Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively).…
Preclinical progress with CHF2819, a novel orally active acetylcholinesterase inhibitor
2002
(-)-(3aS,8aS,1S)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol-2′-ethylphenylcarbamate N-oxide hydrochloride (CHF2819) is a novel, orally active acetylcholinesterase inhibitor (AChEI) for Alzheimer's disease (AD). CHF2819 appears as a selective inhibitor of AChE, being 115 times more potent against this enzyme than butyrylcholinesterase (BuChE). Moreover, CHF2819 appears more selective for inhibiting central (brain) than peripheral (heart) AChE. In vivo studies show that CHF2819 significantly increases acetylcholine (ACh) levels in young adult rat hippocampus in a dose-dependent manner. Moreover, aged animals exhibit a marked increase in hippocampal concentrations of this…
Increased nitrotyrosine plasma levels in relation to systemic markers of inflammation and myeloperoxidase in chronic heart failure
2009
The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO …
Wood-derived estrogens: studies in vitro with breast cancer cell lines and in vivo in trout.
1996
The wood-derived compound, beta-sitosterol (purity > 90%), was shown to be estrogenic in fish. It induced the expression of the vitellogenin gene in the liver of juvenile and methyltestosterone-treated rainbow trout. Structural similarities to beta-sitosterol notwithstanding, cholesterol, citrostadienol, beta-sitostanol, and 5-androstene-3 beta,17 beta-diol, an estrogenic member of the androstenic steroid group, were inactive. An abietic acid mixture (37% abietic acid, 6% dehydroabietic acid, and a remainder of unknown compounds) showed slight hormonal activity in feed, but it was completely inactive when given intraperitoneally in implants. The estrogenic component of the abietic acid prep…
Protein kinase C-inhibiting properties of the losartan metabolite EXP3179 make the difference.
2009
The inhibition of the renin-angiotensin axis with the angiotensin II (ATII) receptor blockers, such as losartan, candesartan, and valsartan, has been demonstrated, similar to angiotensin-converting enzyme inhibitors, to reduce mortality in patients with arterial hypertension, chronic congestive heart failure, and acute myocardial infarction.1 Initially, the ATII receptor antagonist losartan helped to demonstrate new classes of ATII receptors and substantially expanded our knowledge about the cardiovascular effects of the renin-angiotensin-aldosterone system and its effector peptide ATII. Researchers dealing with this compound soon revealed that, beyond its antihypertensive effects attribute…
Inducibility of the avidin gene by progesterone is suppressed during estrogen-induced cytodifferentiation.
1992
Abstract We have studied epithelial differentiation of the chick oviduct as induced by diethylstilbestrol (DES) and 17β-estradiol (E 2 ). The proportion of goblet cells in the oviduct was slightly higher after E 2 than after DES treatment. Also avidin induction by progesterone was stronger following DES than E 2 priming. In the estrogen pretreated oviduct epithelium, avidin expression was induced by progesterone in the surface epithelial cells, protodifferentiated gland cells and tubular gland cells, but not in goblet cells. During prolonged estrogen treatment, however, the inducibility of avidin by progesterone ceased in tubular gland cells but not in surface epithelial cells. The estrogen…
The role of fibrate treatment in dyslipidemia: an overview.
2012
Dyslipidemia, and especially atherogenic dyslipidemia, a combination of small low-density lipoproteins cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) concentrations, represents a major cardiovascular (CV) risk factor. Nuclear receptor peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid metabolism; PPAR ligands are used to treat dyslipidemias. Fibrates have a major impact on TG metabolism as well as on modulating LDL size and subclasses. Fibrates target atherogenic dyslipidemia by increasing plasma HDL-C concentrations and decreasing small dense LDL (sdLDL) particles and TGs, thus contributin…
CHF2819: Pharmacological profile of a novel acetylcholinesterase inhibitor
2002
CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administ…
The Inhibitory Effects of Prednisone, 16-Methylen-Prednisolone, and Acth on Con-A Induced Lymphokines (Interferon-Y) as Measured by the Chemiluminesc…
1988
When lymphocytes are stimulated with mitogens or antigens they are enhanced via a cascade of lymphokines to produce interferon-y (IFN-y). IFN-y augments the H2O2 secretion of human monocytes which indirectly can be measured by chemiluminescence. We tested prednisone, 16-methylen-prednisolone and ACTH for their effect to inhibit the Con-A induced stimulation of the chemiluminescence-activity. All three hormones inhibited significantly the stimulation: prednisone up to 52.5% (concentration = 150 micrograms/ml, p = 0.000005), 16-methylen-prednisolone up to 22.5% (concentration = 2.5 micrograms/ml, p = 0.006) and ACTH up to 33% (concentration = 10 micrograms/ml, p = 0.0036).
Constitutive androstane receptor activation stimulates faecal bile acid excretion and reverse cholesterol transport in mice.
2010
The constitutive androstane receptor (CAR) is a nuclear receptor expressed in the liver and involved in xenobiotic metabolism. The aim of this study was to assess whether pharmacological CAR activation could affect neutral sterol and bile acid elimination under conditions of cholesterol overload.Wild type, Car-/-, ApoE-/-, and low-density lipoprotein receptor (Ldlr)-/- mice fed a western-type diet were treated with the CAR agonist TCPOBOP.CAR activation was associated with a decrease in faecal cholesterol output related to the repression of the Abcg5/g8 cholesterol transporters. In contrast, TCPOBOP treatment induced a marked increase (up to three fold, p0.01) in the elimination of faecal b…