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1.
Int J Obes (Lond) ; 40(11): 1662-1670, 2016 11.
Article in English | MEDLINE | ID: mdl-27339607

ABSTRACT

BACKGROUND/OBJECTIVES: Long-term success of weight loss diets might depend on how the appetite regulatory system responds to energy restriction (ER). This study determined the effect of 24 h severe ER on subjective and hormonal appetite regulation, subsequent ad libitum energy intake and metabolism. SUBJECTS/METHODS: In randomised order, eight overweight or obese males consumed a 24 h diet containing either 100% (12105 (1174 kJ; energy balance; EB) or 25% (3039 (295) kJ; ER) of estimated daily energy requirements (EER). An individualised standard breakfast containing 25% of EER (3216 (341) kJ) was consumed the following morning and resting energy expenditure, substrate utilisation and plasma concentrations of acylated ghrelin, glucagon-like peptide-1 (GLP-17-36), glucose-dependant insulinotropic peptide (GIP1-42), glucose, insulin and non-esterified fatty acid (NEFA) were determined for 4 h after breakfast. Ad libitum energy intake was assessed in the laboratory on day 2 and via food records on day 3. Subjective appetite was assessed throughout. RESULTS: Energy intake was not different between trials for day 2 (EB: 14946 (1272) kJ; ER: 15251 (2114) kJ; P=0.623), day 3 (EB: 10580 (2457) kJ; 10812 (4357) kJ; P=0.832) or day 2 and 3 combined (P=0.693). Subjective appetite was increased during ER on day 1 (P<0.01), but was not different between trials on day 2 (P>0.381). Acylated ghrelin, GLP-17-36 and insulin were not different between trials (P>0.104). Post-breakfast area under the curve (AUC) for NEFA (P<0.05) and GIP1-42 (P<0.01) were greater during ER compared with EB. Fat oxidation was greater (P<0.01) and carbohydrate oxidation was lower (P<0.01) during ER, but energy expenditure was not different between trials (P=0.158). CONCLUSIONS: These results suggest that 24 h severe ER does not affect appetite regulation or energy intake in the subsequent 48 h. This style of dieting may be conducive to maintenance of a negative EB by limiting compensatory eating behaviour, and therefore may assist with weight loss.


Subject(s)
Appetite Regulation/physiology , Caloric Restriction , Energy Intake/physiology , Energy Metabolism/physiology , Obesity/physiopathology , Acylation/physiology , Adult , Appetite/physiology , Blood Glucose/metabolism , Body Mass Index , Feeding Behavior , Ghrelin/metabolism , Glucagon-Like Peptide 1/metabolism , Humans , Male , Obesity/metabolism , Postprandial Period/physiology , Prospective Studies , United Kingdom
2.
Rev Sci Instrum ; 81(10): 10E528, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21034056

ABSTRACT

This article describes the results of spatial heterodyne Doppler "coherence imaging" of carbon ion flows in the divertor region of the DIII-D tokamak. Spatially encoded interferometric projections of doubly ionized carbon emission at 465 nm have been demodulated and tomographically inverted to obtain the spatial distribution of the carbon ion parallel flow and emissivity. The operating principles of the new instruments are described, and the link between measured properties and line integrals of the flow field are established. An iterative simultaneous arithmetic reconstruction procedure is applied to invert the interferometric phase shift projections, and the reconstructed parallel flow field amplitudes are found to be in reasonable agreement with UEDGE modeling.

4.
J Med Chem ; 31(5): 913-9, 1988 May.
Article in English | MEDLINE | ID: mdl-2966246

ABSTRACT

A number of tertiary and secondary homoallylic amines, i.e. (Z)- and (E)-4-(4-bromophenyl)-4-(3-pyridyl)-3-buten-1-ylamines, were synthesized in diastereomerically pure forms. The compounds were evaluated as neuronal norepinephrine (NE) and serotonin (5-HT) uptake inhibitors under in vitro and ex vivo conditions and compared with the tricyclics amitriptyline and nortriptyline having homoallylic side chains and with the corresponding diastereomers in the zimeldine series having allylic side chains. The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z). Likewise, the selectivity profile of the homoallylic (3E, 4E) and the allylic (1E, 2E) derivatives was comparable. In general, the homoallylic compounds were less potent inhibitors than their allylic counterparts. The similarities and discrepancies were evaluated in terms of conformational preferences determined by CAMSEQ molecular mechanics calculations. Homonorzimeldine (4Z) can accommodate energetically favored, but less populated, conformations having amino nitrogen atom to aromatic ring center distances comparable to those in norzimeldine. These facts correlate to retained 5-HT selectivity but diminished potency of 4Z compared to 2Z.


Subject(s)
Neurotransmitter Uptake Inhibitors/chemical synthesis , Norepinephrine/metabolism , Serotonin/metabolism , Zimeldine/analogs & derivatives , Animals , Brain/drug effects , Brain/metabolism , Chemical Phenomena , Chemistry , In Vitro Techniques , Male , Mice , Rats , Rats, Inbred Strains , Stereoisomerism , Structure-Activity Relationship , Synaptosomes/drug effects , Synaptosomes/metabolism , Zimeldine/chemical synthesis , Zimeldine/pharmacology
5.
Drug Des Deliv ; 1(1): 23-37, 1986 Aug.
Article in English | MEDLINE | ID: mdl-2908221

ABSTRACT

Low energy conformations and the pathways between them have been calculated for nisoxetine (N-methyl-3-phenyl-3-(o-methoxyphenoxy)-propylamine), (I), a selective inhibitor of neuronal reuptake of norepinephrine, and fluoxetine (N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine), (II), a selective inhibitor of neuronal reuptake of serotonin. Results are presented as a series of energy maps and ORTEP drawings. Conformational preferences of the protonated forms and preferred conformations in aqueous solution are also established. The CAMSEQ empirical potential method was used throughout. Both the nisoxetine and fluoxetine systems are shown to exhibit the known 'folded-extended' conformational preferences of the phenethylamines. It is suggested that the observed conformational variation between the two systems may play a role in the pharmacological differences between nisoxetine and fluoxetine.


Subject(s)
Fluoxetine/analogs & derivatives , Fluoxetine/analysis , Neurotransmitter Agents/metabolism , Norepinephrine/antagonists & inhibitors , Serotonin Antagonists/analysis , Chemical Phenomena , Chemistry, Physical , Fluoxetine/pharmacology , Molecular Conformation , Norepinephrine/metabolism , Phenethylamines/analysis , Serotonin/metabolism , Solutions , Thermodynamics
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