A small-molecule fusion inhibitor of influenza virus is orally active in mice.

Recent characterization of broadly neutralizing antibodies (bnAbs) against influenza virus identified the conserved hemagglutinin (HA) stem as a target for development of universal vaccines and therapeutics. Although several stem bnAbs are being evaluated in clinical trials, antibodies are generally unsuited for oral delivery. Guided by structural knowledge of the interactions and mechanism of anti-stem bnAb CR6261, we selected and optimized small molecules that mimic the bnAb functionality.

Potent peptidic fusion inhibitors of influenza virus.

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114).

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this.

Cerebral imaging in infectious endocarditis: A clinical study.

Background: Because neurological failure is the most frequent extra-cardiac complication in Infectious Endocarditis (IE), a brain computerised tomography (CT) scan is usually performed. The benefits of magnetic resonance imaging (MRI) have not been clearly established. This study aims to clarify the prevalence and type of cerebral lesions in IE detected using MRI and to compare them with those detected using CT scans.

The effect of nicotine induced behavioral sensitization on dopamine D1 receptor pharmacology: An in vivo and ex vivo study in the rat.

Behavioral sensitization is a phenomenon which can develop following repeated intermittent administration of a range of psychostimulants, and other compounds, and may model neuroplastic changes seen in addictive processes and neuropsychiatric disease. The aim of the present study was to investigate the effect of dopamine D1 receptor (D1R) ligands on nicotine-induced behavioral sensitization and their molecular consequences in the striatum. Wistar rats were chronically treated (5 days) with vehicle or nicotine (0.

Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro.

Cyclic-adenosine monophosphate (cAMP) plays an important role in cell signalling and is widely used as a marker for receptor activation and as a target for treating various diseases. In this paper we present the development and validation of a new method for the determination of cAMP and ATP (adenosine triphosphate) and other nucleotides in a biological system by combining zwitterionic hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS). The HILIC-MS/MS method was developed for the simultaneous quantitative analysis of cAMP and ATP, and was validated by assessment of linearity (over a range from 0.

WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one]: a novel dopamine D2 receptor partial agonist/serotonin reuptake inhibitor with preclinical antipsychotic-like and antidepressant-like activity.

The preclinical characterization of WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one] is described. In vitro binding and functional studies revealed highest affinity to the D(2) receptor (D(2L) K(i), 4.0 nM) and serotonin transporter (K(i), 7.

Twelve year observation of primary and secondary antibiotic-resistant Helicobacter pylori strains in children.

Background: The effectiveness of Helicobacter pylori eradication regimens is influenced by antibiotic susceptibility of infecting strains. Data concerning antibiotic resistance in children are limited. We report the evolution of primary and secondary resistance in a series of Belgian children during the last 12 years.

Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds.

Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor.

Tocopherol mobilization during intensive exercise.

This work shows that the level of plasma tocopherol (vitamin E) which has free radical scavenging properties rises significantly during intensive exercise. It is proposed that mobilization of tocopherol could help to prevent lipoperoxidation phenomena occurring in exercising skeletal muscle. A hypothetical mechanism relating to a lipolysis effect is discussed to explain this mobilization.

Thromboxane and prostacyclin release in adult respiratory distress syndrome.

Plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (greater than 140 pg/ml plasma) TXB2 values were found in 52/84 patients.

Stimulation of cyclooxygenase by activated human neutrophils is enhanced by uric acid.

Activated human neutrophils supernatant enhances prostanoids production by bull seminal cyclooxygenase (455% of control). Superoxide anion and hydrogen peroxide are not involved in this stimulation, in these experimental conditions. Myeloperoxidase (by its hemic nature) and HPETEs (by their -OOH function) could trigger cyclooxygenase.

[The relation between polyunsaturated fatty acids and cardio-vascular accidents. I. Study of fatty acid components phospholipids].

Blood plasma lipids of women about seventy years old who had suffered from cardiovascular diseases (AVC) were studied and compared with the plasma lipids of women of about the same age without cardiac troubles. A great difference appears in the unesterified fatty acids of the phospholipids from cardiac women: we have observed a decreasing level of polyunsaturated fatty acids with a carbon chain of more than 18 carbons, and a decreasing ratio between the total concentration of the two precursors (linoleic acid omega and alpha-linolenic acid omega 3) and the total concentration of their long chain polyunsaturated derived fatty acids. On the contrary, we did not observe any significant variation of the unesterified fatty acid level in the plasma.