Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate.

Elevation of the plasma levels of ()-lactate (Lac) and/or ()-beta-hydroxybutyrate (BHB) occurs naturally in response to strenuous exercise and prolonged fasting, respectively, resulting in millimolar concentrations of these two metabolites. It is increasingly appreciated that Lac and BHB have wide-ranging beneficial physiological effects, suggesting that novel nutritional solutions, compatible with high-level and/or sustained consumption, which allow direct control of plasma levels of Lac and BHB, are of strong interest. In this study, we present a molecular hybrid between ()-lactate and the BHB-precursor ()-1,3-butanediol in the form of a simple ester referred to as .

No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

Introduction: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.

Methods: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers.

Description of an activity-based enzyme biosensor for lung cancer detection.

Background: Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity.

Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated in bronchial lavage as a diagnostic biomarker of lung cancer.

Kinetic Energy Density as a Predictor of Hydrogen-Bonded OH-Stretching Frequencies.

This work considers the nature of the intermolecular hydrogen bond in a series of 15 different complexes with OH donor groups and N, O, P, or S acceptor atoms. To complement the existing literature, room-temperature gas-phase vibrational spectra of the methanol-pyridine, ethanol-pyridine, and 2,2,2-trifluoroethanol-pyridine complexes were recorded. These complexes were chosen, as they exhibit hydrogen bonds of intermediate strength as compared to previous investigations that involved strong or weak hydrogen bonds.

Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands.

Analysis of the roles of the short chain fatty acid receptor, free fatty acid 3 receptor (FFA3), has been severely limited by the low potency of its endogenous ligands, the crossover of function of these on the closely related free fatty acid 2 receptor, and a dearth of FFA3-selective synthetic ligands. From a series of hexahydroquinolone-3-carboxamides, we demonstrate that 4-(furan-2-yl)-2-methyl-5-oxo-N-(o-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide is a selective and moderately potent positive allosteric modular (PAM)-agonist of the FFA3 receptor. Modest chemical variations within this series resulted in compounds completely lacking activity, acting as FFA3 PAMs, or appearing to act as FFA3-negative allosteric modulators.

Study of the thermal nitridation of nanocrystalline Ti(OH)4 by X-ray and in situ neutron powder diffraction.

In situ neutron diffraction measurements of nanocrystalline titanium oxynitrides were performed, as a function of temperature and time, to explore the nitrogen/oxygen substitution mechanism occurring during their synthesis by reaction of gaseous ammonia with nanocrystalline Ti(OH)(4). These neutron diffraction experiments are supported by chemical analysis and X-ray diffraction, allowing the description of the structural variations and ordering process between the Ti(O/N)(2) anatase and the Ti(O/N) rock-salt phases. Our results show that the formation of the Ti(O/N) rock-salt phase goes along with the creation of vacancies on the Ti sites and that the N/O substitution proceeds but without N/O ordering.

Explanation for main features of structure-genotoxicity relationships of aromatic amines by theoretical studies of their activation pathways in CYP1A2.

Aromatic and heteroaromatic amines (ArNH(2)) represent a class of potential mutagens that after being metabolically activated covalently modify DNA. Activation of ArNH(2) in many cases starts with N-hydroxylation by P450 enzymes, primarily CYP1A2. Poor understanding of structure-mutagenicity relationships of ArNH(2) limits their use in drug discovery programs.

Deuterium isotope effects on 13C chemical shifts of nitromalonamide.

The OH chemical shift of the enol form of nitromalonamide is found at 18.9 ppm both in DMSO-d(6) and in DMF-d(7) indicating a very strong hydrogen bond. The OH chemical shift is insensitive to temperature changes.

Total synthesis of (-)-7-epicylindrospermopsin, a toxic metabolite of the freshwater cyanobacterium aphanizomenonovalisporum, and assignment of its absolute configuration.

[reaction: see text] The Z and E nitrones 38 and 39 from condensation of aldehyde 20 with hydroxylamine 36 underwent intramolecular dipolar cycloaddition to give the substituted 1-aza-7-oxobicyclo[2.2.1] heptanes 40 and 41 in a ratio of 2:1, respectively.

The human SH-SY5Y neuroblastoma cell-line expresses a functional P2X7 purinoceptor that modulates voltage-dependent Ca2+ channel function.

Fura-2 imaging of purinergic stimulation of non-differentiated neuronal human SH-SY5Y cells resulted in a rapid elevation in intracellular Ca2+ ([Ca2+]i) that was dependent on extracellular Ca2+. The rank order of agonists (200 micro m) was as follows: 2',3'-O-(4-benzoyl-benzoyl)-ATP (BzATP) > ATP4- > ATP; whereas 2-(methylthio)-ATP, ADP, UTP and alpha,beta-methylene-ATP and beta,gamma-methylene-ATP were ineffective. The response to BzATP was inhibited by pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic-acid (PPADS, 1 micro m), 1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-l-tyrosyl)-4-phenylpiperazine (KN-62, 100 nm) and 8-(3-benzamido-4-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic-acid (suramin, 200 micro m).

Nucleophilic addition reaction in coordinated non-linear pseudohalides: experimental charge density analysis in trans-bis(cyanamidonitrato-N:O)bis-(imidazole-N(3))copper(II) complex.

The experimental crystal charge density of the complex [Cu(iz)(2)(can)(2)] (I) (where iz = imidazole, can = cyanamidonitrate anion), [Cu(C(3)H(4)N(2))(2)(CN(3)O(2))(2)], crystallizing in centrosymmetric space group P2(1)/c, has been determined at 120.0 (2) K, using Hansen and Coppens' aspherical atom multipole model. The central Cu atom is pseudo-octahedrally coordinated by four N atoms in an equatorial plane [two from iz molecules, 1.

Experimental pretargeting studies of cancer with a humanized anti-CEA x murine anti-[In-DTPA] bispecific antibody construct and a (99m)Tc-/(188)Re-labeled peptide.

The aim of this study was to localize (99m)Tc and (188)Re radionuclides to tumors, using a bispecific antibody (bsMAb) in a two-step approach where the radionuclides are attached to novel peptides incorporating moieties recognized by one arm of the bsMAb. A chemically cross-linked human/murine bsMAb, hMN-14 x 734 (Fab' x Fab'), anti-carcinoembryonic antigen [CEA] x anti-indium-DTPA was prepared as a prelude to constructing a fully humanized bsMAb for future clinical application. N,N'-o-Phenylenedimaleimide was used to cross-link the Fab' fragments of the two antibodies at their hinge regions.

Patellofemoral pain syndrome in athletes: a 5.7-year retrospective follow-up study of 250 athletes.

Two hundred fifty athletes from a sports clinic, 122 (49%) females and 128 (51%) males (mean age 21.1 years), who were diagnosed as having patellofemoral pain syndrome (PFPS) and were instructed to practice vastus medialis training, returned a completed questionnaire after an average of 5.7 years' follow-up.