169,816 research outputs found
Seborrheic Keratosis, Keratotic Type, of the External Auditory Canal
No full text[No abstract available
Pyrrolidinyl benzofurans and benzodioxanes: Selective α4β2 nicotinic acetylcholine receptor ligands with different activity profiles at the two receptor stoichiometries
No full textA series of racemic benzofurans bearing N-methyl-2-pyrrolidinyl residue at C(2) or C(3) has been synthesized and tested for affinity at the α4β2 and α3β4 nicotine acetylcholine receptors (nAChRs). As previously reported for the benzodioxane based analogues, hydroxylation at proper position of benzene ring results in high α4β2 nAChR affinity and α4β2 vs. α3β4 nAChR selectivity. 7-Hydroxy-N-methyl-2-pyrrolidinyl-1,4-benzodioxane (2) and its 7- and 5-amino benzodioxane analogues 3 and 4, which are all α4β2 nAChR partial agonists, and 2-(N-methyl-2-pyrrolidinyl)-6-hydroxybenzofuran (12) were selected for functional characterization at the two α4β2 stoichiometries, the high sensitivity (α4)2(β2)3 and the low sensitivity (α4)3(β2)2. The benzene pattern substitution, which had previously been found to control α4β2 partial agonist activity and α4β2 vs. α3β4 selectivity, proved to be also involved in stoichiometry-selectivity. The 7-hydroxybenzodioxane derivative 2 selectively activates (α4)2(β2)3 nAChR, which cannot be activated by its 5-amino analogue 4. A marginal structural modification, not altering the base pyrrolidinyl benzodioxane scaffold, resulted in opposite activity profiles at the two α4β2 nAChR isoforms providing an interesting novel case study
4-, 5-, 6-, and 7-Hydroxybenzofuran: a unified strategy for a two-step synthesis of versatile benzofuranic building blocks
No full textOver several decades, many different strategies have been reported to prepare 4-, 5- , 6-, and 7- hydroxybenzofuran (HBF), which are very important synthetic intermediates. Interested in addition of their 2- lithiated O-protected derivatives to transient 1-pyrroline as a straightforward way to nicotinoids, we have developed a unique two-step procedure to obtain 4-, 5- , 6-, and 7-HBF from 2,6-, 2,5-, 2-4- and 2,3- dihydroxyacetophenone, respectively, by conversion into 4-, 5-, 6- and 7-hydroxybenzofuranone and successive reduction of these latter with lithium borohydride. On the basis of the overall yields, the number of steps and the availability of the starting materials, such a synthetic strategy can be advantageously compared with the literature methods, here briefly reviewed, developed to synthesize the four HBFs.(piture presented
Exploring perceptive drivers and barriers to the consumption of plant-based alternatives
No full textNowadays, a major global challenge is to find healthy and sustainable alternative food sources to meet the growing demand for food. One of the strategies adopted to reduce the environmental impact of the food system is the development of plant-based foods used as substitutes for animal products (i.e. plant-based meat analogues, plant-based dairy alternatives). Although consumers are increasingly aware of the environmental impact of their food choices, barriers to the transition towards these products still exist. In this context, the aims of this study were to: a) obtain a sensory mapping of animal product alternatives of the Italian market b) identify the main perceptive drivers of acceptability and rejection of plant-based products.
A sample of adult consumers (n ≥ 100; age > 18 years) balanced according to gender and age was recruited. Consumers were asked to taste and rate their overall liking of commercial plant-based foods and to perform a Check-All-That-Apply (CATA) task to describe the samples. Consumers also completed questionnaires to investigate their food consumption behaviour.
Through this study, a sensory database of plant-based products was defined based on compositional, nutritional and sensory characteristics. This database showed that there is a large diversity within the same food category with reference to the raw ingredients used and the sensory characteristics. Furthermore, through Principal Coordinate Analysis, obtained by linking liking data with CATA descriptions, the drivers of liking and rejection towards these food products were identified. Further analyses are in progress to verify the effect of consumers eating behaviour on the acceptability of these products.
The present study provides useful information for food companies for identifying potential reformulation opportunities and product development. Indeed, the optimization of the sensory and nutritional properties of plant-based food is a key strategy to improve its liking and to promote its consumption with consequent environmental and health benefits
Determinants for α4β2 vs. α3β4 Subtype Selectivity of Pyrrolidine-Based nAChRs Ligands: A Computational Perspective with Focus on Recent cryo-EM Receptor Structures
No full textThe selectivity of α4β2 nAChR agonists over the α3β4 nicotinic receptor subtype, predominant in ganglia, primarily conditions their therapeutic range and it is still a complex and challenging issue for medicinal chemists and pharmacologists. Here, we investigate the determinants for such subtype selectivity in a series of more than forty α4β2 ligands we have previously reported, docking them into the structures of the two human subtypes, recently determined by cryo-electron microscopy. They are all pyrrolidine based analogues of the well-known α4β2 agonist N-methylprolinol pyridyl ether A-84543 and differ in the flexibility and pattern substitution of their aromatic portion. Indeed, the direct or water mediated interaction with hydrophilic residues of the relatively narrower β2 minus side through the elements decorating the aromatic ring and the stabilization of the latter by facing to the not conserved β2-Phe119 result as key distinctive features for the α4β2 affinity. Consistently, these compounds show, despite the structural similarity, very different α4β2 vs. α3β4 selectivities, from modest to very high, which relate to rigidity/extensibility degree of the portion containing the aromatic ring and to substitutions at the latter. Furthermore, the structural rationalization of the rat vs. human differences of α4β2 vs. α3β4 selectivity ratios is here proposed
Acute Hypobaric-Hypoxia Challenge and Salivary Cortisol and DHEA-S in Healthy Male Subjects
No full textPONTREMOLESI S, BISELLI R, CINIGLIO APPIANI G, D'AMELIO R, SIMONA S, PATACCHIOLI FR. Acute hypobaric-hypoxia challenge and salivary cortisol and DHEA-S in healthy male subjects. Aviat Space Environ Med 2012; 83:637-42. Background: Hypobaric hypoxia is a stressful emergency situation that can cause a degradation of the sensory, motor, and higher cognitive functions necessary for safe flight. Methods: We studied the salivary cortisol and dehydroepiandrosterone-sulfate (DHEA-S) concentrations of 12 healthy male military aviators (AV) exposed to an altitude-induced hypoxia challenge in a hypobaric chamber. A matched control group (C) of eight flight physiology instructors wearing oxygen masks during the challenge was studied. Salivary samples were collected every 2 h on 3 experimental days (the day before, the day of, and the clay after the hypobaric chamber challenge). Results: In the AV group, salivary cortisol concentrations showed a statistically significant increase from 5.42 +/- 0.15 measured at 08:30 to 11.37 +/- 1.86 ng ml(-1) during the hypobaric chamber challenge and a statistically significant increase in DHEA-S was also measured (from 3.15 +/- 0.42 ng . ml(-1) at 08:30 to 5.99 +/- 0.15 ng . ml(-1)). The day after the challenge, the concentrations of both hormones were comparable to those measured the day before; neither C nor AV showed any disturbances of the physiological diurnal fluctuations of cortisol and DHEA-S. No differences were found among the cortisol/DHEA-S ratios measured during the 3 experimental days in the AV group. Discussion: In spite of having experienced a psycho-physical stress, the AVs did not show any dysregulation of the diurnal fluctuations of cortisol and DHEA-S, thus presenting a good level of stress resilience. Data presented in this paper are consistent with recent literature suggesting a stress-buffering role of DHEA-S
Exploring consumer attitudes toward plant-based fish analogues for sustainable dietary choices
No full textAim:
The food system is facing numerous challenges in advancing environmental sustainability, human health, and animal welfare. A promising solution is the transition towards plant-based diet. Nevertheless, the perceived poor sensory quality of new plant-based products and the resistance to changing eating habits remain significant hurdles for consumers.
Method:
165 consumers (48.5% F; 18-65 years) were clustered based on their attitudes towards food purchase, quality, preparation and consumption using the Food Related Lifestyle questionnaire. The segments of consumers were chracterised according to socio-demographic variables, personality traits and frequency of consumption of plant-based alternatives products.
Results:
Three clusters of conumers were identified: 1) The largest and oldest group "Careful consumers" (55.1%) prioritized health aspects and carefully read label information. They placed greater importance on food shopping, price criteria and utilized shopping lists for their purchases. They also showed a higher consumption of plant-based analogues. 2) 'Hedonic consumers' (26.1%) were mainly young consumer inclined to try new food products. Their attention is focused on the sensory aspects and food taste; finally 3) 'Uninvolved consumers' (18.8%) showed less interested in food-related activities and information and are less interested in cooking. They exhibit higher neophobia index and they rank among the least frequent consumers of analogues products.
Conclusion:
Three distinct groups of consumers with significantly different behaviour and attitudes towards the consumption of plant-based analogues were identified. The findings from this study offer valuable insights for the food industry, enabling more targeted communication and educational efforts aimed at promoting sustainable nutrition
ALPHA4BETA2 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS: FROM SUBTYPE SELECTIVE TO STOICHIOMETRIC ISOPHORM SELECTIVE PARTIAL AGONISM.
No full textThis PhD thesis focuses on the study of the α4β2 nicotinic acetylcholine receptors (nAChRs). This dissertation is divided into two parts. The first part is centred on the design, synthesis, and biological evaluation of compounds selective for the orthosteric and unorthodox binding sites of the α4β2 nAChRs. In the second part, attention is paid to the study of a photoactivatable α4β2 nAChRs full agonist.
Part 1
The first goal of Part 1 was the mutational studies of Ser108 residue of the hydrophilic pocket of the β2(-) side of the α4β2 orthosteric binding site with the purpose of studying the importance of the hydroxyl group of serine residue and the steric encumbrance in the pocket. For this reason, binding experiments were performed on the heterologously expressed human α4β2 receptor and its three Ser108àLeu, Ser108àPhe and Ser108àAla mutants using the most promising partial agonists synthesized previously.
The second goal was the synthesis and pharmacological evaluation of the naked and hydroxy/methoxy decorated benzofuran-based compound in order to study the implications of the flexibility reduction, abolishment of cycle stereogenic and of the one of the two oxygen in comparison with previously tested benzodioxane derivatives. Subsequently, the most promising benzodioxane compounds and the obtained benzofuran derivatives were evaluated for their affinity and activity on the two distinct α4β2 nAChR isoforms: (α4)2(β2)3 and (α4)3(β2)2.
The third goal was the study of the in vivo effects of prolinol aryl ethers and pyrrolidinyl benzodioxanes full and partial agonists. These compounds were tested for their effects on zebrafish behaviour. In particular, full agonists were tested for their ability to improve spatial memory and attention, and partial agonist for its ability to block the rewarding effects of nicotine and therefore its potential use for smoking cessation.
The fourth goal was the design, synthesis and pharmacological evaluation of selective agonists for the α4α4 unorthodox binding site of the α4β2 nAChR based on the structure of NS9283, an α4α4selective compound, described in the literature. The main aim was to identify new hit
V
compounds potentially selective at the (α4)3(β2)2 receptor isoform with a better pharmacological profile.
Part 2
Regarding the second part of this thesis, it focuses on the synthesis of a photoactivatable α4β2 nAChR full agonist with the purpose to spatiotemporally control its release with light at the specific site of action. To follow this strategy, 8-bromo-7-hydroxy-2-methylquinoline (BHQ) and 8-cyano-7-hydroxy-2-methylquinoline (CyHQ) protecting groups were synthesized and used to cage a previously synthesized full agonist. Subsequently, its release after the irradiation with the UV light at 365 nm was followed using HPLC in order to obtain a full photo- chemical characterization of the caged compounds to get necessary information for in vitro/in vivo experiments
Sensory drivers of liking and consumer emotional responses to plant-based fish vs fish
No full textAim:
Today, the demand for alternative seafood is rapidly increasing. Plant-based breaded fish fillets and fingers are highly popular imitations, yet little is known about consumer experiences with these products. This study aimed to: a) explore sensory, liking, and emotional responses to commercially available plant-based breaded fish alternatives; and b) categorize consumers using an innovative clustering method based on cata and liking data (CLUSCATA-liking).
Method:
The present research explored plant-based/animal-based breaded fish product category using a multi-variable research strategy where 104 consumers (52% Female; 27.7±8.9 y.o.) tasted samples for degree of liking/disliking and described their perceived sensory characteristics using check-all-that-apply (CATA) questions. A product-specific questionnaire was developed to evaluated the emotional response associated with the product consumption.
Results:
GLM results showed a significant effect of samples on overall liking (F=22.0; p<0.0001). Although animal-based samples were the most liked, samples formulated with dehydrated rice flakes, rice or texturised wheat protein were well accepted (Ls-mean=53.6-62.1). In contrast, samples made with soy and rice protein were disliked (<50) due to perceived bitterness, legume and vegetable odour and off-flavours. The differences among the samples were further emphasized based on the associated emotions. Animal-based samples were associated with emotions of satisfaction and happiness, while plant-based samples elicited negative emotions such as disappointment, disgust and indifference. Only the sample containing textured wheat protein evoked positive emotions (surprise, curiosity, novelty). Preliminary consumer segmentation using Cluscata-liking identified two distinct clusters with differing preferences for plant-based samples. Further analyses are in progress to characterise them in terms of the sensory and emotional responses.
Conclusion:
These findings show that incorporating the measurement of implicit variables such as emotions alongside liking leads to enhanced product differentiation. Through the multi-response approach adopted in this study, it was possible to obtain a comprehensive product characterisation, contributing to a better understanding of the factors driving the liking of plant-based fish alternatives, valuable for product development and marketing strategies
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