Assessing the discharge instructing in the emergency department: Patient perspective.

Objective: The objective of the study is to assess how well the emergency department (ED) personnel succeed in instructing the patient at discharge.

Methods: In November and December 2016 at Peijas Hospital ED, Finland, a structured questionnaire was conducted during a phone interview on patients the day after discharge.

Results: A total of 132 patients interviewed.

The need for a worldwide consensus for cell line authentication: Experience implementing a mandatory requirement at the International Journal of Cancer.

Cell lines are used in life science research worldwide as biological surrogates. All cell lines are subject to major limitations when used as research tools, including (i) cross-contamination with other cells cultured in the same laboratory environment and (ii) evolution in vitro that renders a given cell line inappropriate as a surrogate for a specific biological hypothesis. There is ample evidence that cross-contamination or phenotypic drift of cells in culture can generate irreproducible or misleading data.

Long-standing oral mucosal lesions in solid organ-transplanted children-a novel clinical entity.

Background: Acute oral angioedema is well documented in young pediatric liver-transplanted patients. This is a report of an identified novel entity of long-standing oral mucosal lesions (OML) in children who had undergone solid organ transplantation.

Methods: In conjunction with routine medical follow-ups, all solid organ-transplanted children were examined annually for OML.

Oral health status in a group of children and adolescents with myotonic dystrophy type 1 over a 4-year period.

Aim: The aim of this longitudinal study was to evaluate changes in oral health, orofacial function, and dental care in children with myotonic dystrophy type 1 (DM1) in comparison with a control group.

Methods: Thirty-six DM1 patients and 33 control patients out of originally 37 in each group were examined on two occasions about 4 years apart. Caries, plaque, and gingivitis were registered, mouth opening capacity assessed and the ability to cooperate in dental treatment estimated.

Oral health in children and adolescents with myotonic dystrophy.

Myotonic dystrophy or dystrophia myotonica (DM) is a hereditary neuromuscular multisystem disease with a varying clinical expressivity and severity. The objective of this study was to assess the oral health in children with myotonic dystrophy and to compare it with a control group. Fifty-six DM patients, aged 2.

A new type of prodrug of catecholamines: an opportunity to improve the treatment of Parkinson's disease.

After decades of research around dopamine agonists, we have found a promising compound in S-PD148903 that represents a new type of prodrug, which in the rat is bioactivated to the catecholamine S-5,6-diOH-DPAT, known to display mixed dopamine D(1)/D(2) receptor agonist properties just like apomorphine. This prodrug has an enone structure which by an oxidative bioactivation mechanism is converted to the corresponding catechol and is delivered enantioselectively into the CNS. This novel concept has the potential to revolutionize the treatment of Parkinson's disease by competing with L-DOPA, the current treatment of choice.

Synthesis and pharmacological evaluation of thiopyran analogues of the dopamine D3 receptor-selective agonist (4aR,10bR)-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl-2H,5H [1]b enzopyrano[4,3-b]-1,4-oxazin-9-ol (PD 128907).

Benzopyranoxazine (+)-7 (PD 128907) is the most dopamine (DA) D3 receptor-selective agonist presently known. The only structural feature which distinguishes 7 from the analogous nonselective naphthoxazines is an oxygen atom in the 6-position. To extend this series of tricyclic DA agonists we used a classic bioisoster approach and synthesized thiopyran analogues of 7, which have a sulfur atom in the 6-position.

New selective and potent 5-HT(1B/1D) antagonists: chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides.

A series of new analogues of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (1; GR127935) as potent and selective 5-HT(1B/1D) antagonists were synthesized and evaluated pharmacologically. Their receptor binding profiles were comparable to that of 1. The 1,3,4-oxadiazole isomer 2 and the 4'-aminocarbonyl and 4'-amidinyl analogues (9 and 10) of 1 had higher affinities at the rat 5-HT(1B) receptor (IC(50) = 0.

New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation.

A series of 2- or 8-trifluoromethylsulfonyloxy (TfO) and 2- or 8-methylsulfonyloxy (MsO) 11-piperazinyldibenzodiazepines, -oxazepines, and -thiazepines were synthesized and evaluated in pharmacological models for their potential clozapine-like properties. In receptor binding assays, the 2-TfO analogues (18a, GMC2-83; 24, GMC3-06; and previously reported GMC1-169, 9a) of the dibenzazepines have profiles comparable to that of clozapine, acting on a variety of CNS receptors except they lack M1 receptor affinity. Introduction of 2-TfO to clozapine leads to compound 9e (GMC61-39) which has a similar binding profile as that of clozapine including having M1 receptor affinity.

5-(Sulfonyl)oxy-tryptamines and ethylamino side chain restricted derivatives. Structure-affinity relationships for h5-HT1B and h5-HT1D receptors.

A number of sulfonic acid ester derivatives of serotonin (5-hydroxytryptamine; 5-HT; 1) were prepared and their affinities are compared to that of the reference compound 5-[[(trifluoromethyl)sulfonyl]oxy]-tryptamine (8b). The structure-affinity relationship (SAFIR) is discussed in terms of in vitro binding for cloned human h5-HT1A, h5-HT1B and h5-HT1D receptors. All tryptamine derivatives exhibited the best affinities for h5-HT1D receptors but still, these were comparatively lower than that of compound 8b.

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes.

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX).

(R)-11-hydroxy- and (R)-11-hydroxy-10-methylaporphine: synthesis, pharmacology, and modeling of D2A and 5-HT1A receptor interactions.

(R)-11-Hydroxyaporphine (2) and (R)-11-hydroxy-10-methylaporphine (3) were synthesized from natural morphine by using new, short, and efficient synthetic sequences. The dopaminergic and serotonergic effects of 2 and 3 were evaluated by use of in vitro and in vivo test systems. The results indicate that 3 is a potent, selective, and efficacious 5-HT1A receptor agonist.

A proposal for the catalytic mechanism in phospholipase C based on interaction energy and distance geometry calculations.

The non-specific phospholipase C from Bacillus cereus preferentially hydrolyses phosphatidylcholine but is also active against phosphatidylserine, phosphatidylethanolamine and at a much lower level, sphingomyelin. A minimal substrate model containing all required structural and configurational elements of a high affinity substrate was docked into the active site. The enzyme-substrate attachment points were from molecular interaction energy calculations using the program GRID and from a previous phosphate inhibitor complex structure.

(S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1- carbaldehyde: a new class of orally active 5-HT1A-receptor agonists.

The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT).

Synthesis of (+)-(R)- and (-)-(S)-5-hydroxy-2-methyl-2-dipropylaminotetralin: effects on rat hippocampal output of 5-HT, 5-HIAA, and DOPAC as determined by in vivo microdialysis.

Racemic 5-methoxy-2-methyl-2-dipropylaminotetralin (3) has been prepared by a short synthetic route, in which the N,N-dipropyliminium perchlorate of 5-methoxy-2-tetralone (4) is a key intermediate. Racemic 3 was resolved by crystallization of the corresponding diastereomeric di-p-toluoyltartrates. The enantiomeric excess (%ee) of the phenolic derivatives of (+)-(R)- and (-)-(S)-3 [(+)-(R)- and (-)-(S)-2] was determined by 1H NMR spectroscopic analysis of the corresponding diastereomeric (-)-(R)-1,1'-binaphthyl-2,2'-diylphosphoric acid salts utilizing 13C satellites.

Synthesis and pharmacology of the enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin.

The enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin (3) have been synthesized and evaluated for activity at central dopamine (DA), 5-hydroxytryptamine, and norepinephrine (NE) receptors, by use of biochemical and behavioral tests in rats. In addition, the affinities of the compounds for striatal [3H]spiroperidol and [3H]N-propylnorapomorphine binding sites were determined. The absolute configuration of the enantiomers was determined by X-ray diffraction of (+)-3.

The effect of hydrogen bonds on the conformation of glycosphingolipids. Methylated and unmethylated cerebroside studied by X-ray single crystal analysis and model calculations.

The conformation and molecular packing of permethylated beta-D-galactosyl-N-octadecanoyl-D-spingosine (cerebroside) was determined by X-ray single crystal analysis at 185 K (R = 0.16). The lipid crystallizes in the orthorhombic space group P2(1)2(1)2(1) with the unit cell dimensions a = 8.

Preferred conformation and dynamics of the glycerol backbone in phospholipids. An NMR and X-ray single-crystal analysis.

The conformation of the glycerol group of a number of diacyl and monoacyl (lyso) phospholipids differing in the chemical nature of the head group was studied by 1H high-resolution NMR and X-ray crystallography. The NMR measurements were carried out with solutions or micellar dispersions of the lipids in deuteriated organic solvents or 2H2O. Both solutions, in which the lipid is present as monomers, and lipid micelles give rise to good high-resolution NMR spectra exhibiting spin coupling hyperfine interactions.

Central dopaminergic and 5-hydroxytryptaminergic effects of C3-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin.

A number of stereochemically well defined C3-methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been synthesized, and their stereochemical characteristics have been studies by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations. The compounds were tested for activity at central 5-HT and dopamine (DA) receptors, by use of biochemical and behavioral tests in rats. In addition, the ability of the cis- and trans-8-hydroxy-3-methyl-2-(di-n-propylamino)tetralins (15 and 11) to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated.

Structural factors of importance for 5-hydroxytryptaminergic activity. Conformational preferences and electrostatic potentials of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and some related agents.

The conformational characteristics of two series of 5-hydroxytryptamine (5-HT) receptor agonists, monophenolic N,N-dialkylated 2-aminotetralins and trans-2-phenylcyclopropylamines, have been studied by a combination of experimental (NMR spectroscopy) and theoretical (molecular mechanics and MNDO calculations) methods. In addition, molecular electrostatic potentials have been calculated for selected conformations and the absolute configuration of the potent 5-HT-receptor agonist (+)-cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin has been determined, by X-ray crystallography of the synthetic precursor, to be 1S,2R. Results obtained are discussed in terms of conformational, steric, and electronic requirements for 5-HT-receptor activation.

C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors.

C1- and C3-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) have been synthesized, and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics (MMP2) calculations. The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (1S,2R)-7-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin [(+)-10] was demonstrated to be sevenfold less potent than (2R)-7-OH-DPAT as a DA receptor agonist.

Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b- octahydrobenzo[f]quinoline : central serotonin stimulating properties.

cis-10-Hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b -octahydrobenzo[f]quinoline (4) is a centrally acting serotonin (5-HT) receptor agonist of moderate potency. Due to its semirigid character and the obvious similarity between (4aR,10bS)-4 and more potent, centrally acting 5-HT receptor agonist cis-(1S,2R)-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (2), we carried out the preparation (via resolution of 6, a precursor of 4) and the pharmacological testing of the enantiomers of 4. We were able to show that the active enantiomers of 4 and 2 coincide in terms of stereochemistry, i.

C3-methylated 5-hydroxy-2-(dipropylamino)tetralins: conformational and steric parameters of importance for central dopamine receptor activation.

C3-Methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations (MMP2). The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (2R,3S)-5-Hydroxy-3-methyl-2-(di-n-propylamino)tetralin [(-)-8] was demonstrated to be a highly potent DA receptor agonist, while the other new compounds were of low potency or inactive.

Conformation and packing properties of membrane lipids: the crystal structure of sodium dimyristoylphosphatidylglycerol.

The conformation and molecular packing of sodium 1,2-dimyristoyl-sn-glycero-phospho-rac-glycerol (DMPG) have been determined by single crystal analysis (R = 0.098). The lipid crystallizes in the monoclinic spacegroup P2(1) with the unit cell dimensions a = 10.