8,503 research outputs found

    Drugs Affecting 5-HT Systems

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    Seminar transcriptIt was in the very early hours of a February morning in 1977 that I first looked down the microscope and saw yellow fluorescence, characteristic of 5-hydroxytryptamine (5-HT) in frozen sections of Octopus brain. After struggling for two years with the capricious fluorescence histochemical technique to locate catecholamines and 5-HT, I finally had a successful result, and the PhD that had seemed a remote possibility for many months finally began to look feasible. Given the enormously important topic of this volume – the discovery and development of drugs affecting 5-HT systems – this small excursion into Octopus neurochemistry might seem irrelevant. However, cephalopod molluscs have played important roles in the history of 5-HT. More than 30000 pairs of posterior salivary glands of Octopus vulgaris were used by Vittorio Erspamer, for the first extraction and identification of enteramine, which was later shown to be identical to serotonin discovered by John Gaddum, and chemically characterized as 5-hydroxytryptamine. Other molluscs have provided some of the most sensitive bioassays for 5-HT, as Gaddum and Paasonen described in 1955, and several participants in this Witness Seminar recollected either using such bioassays or investigating invertebrate pharmacology at the beginning of their careers. Many reflected, however, that invertebrate receptors seemed to be very different from those found in mammals; they had, as David Wallis put it, ‘a parallel pharmacology’. One Witness, Merton Sandler, remembered attending a lecture by Vittorio Erspamer in London in the early 1950s, and being intrigued enough to start work on the degradative enzyme monoamine oxidase, a field which became highly significant for the development of a whole class of therapeutic drugs: the monoamine oxidase inhibitor

    Suboptimal control status of young hypertensive population

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    Abstract The prevalence of hypertension (HT) among young adults aged 18 to 39 years is estimated to be 3.7% to 8.6% worldwide. Although the prevalence of HT in young adults is lower than that of the overall population, those with HT are at substantially increased risk of cardiovascular events compared to those without HT. HT in young adults should be taken with even more caution as longer exposure to higher blood pressure leads to a higher lifetime risk of HT-mediated organ damage. However, young patients with HT show low awareness of HT compared to older patients. Also, they are more prone to show low treatment adherence despite the good efficacy of the treatment. Other risk factors that hinder HT control among young adults include alcohol intake, smoking, low physical activity, emotional stress, job stress, metabolic syndrome, and obesity. This review aimed to illustrate the suboptimal control status of the young hypertensive population and to propose strategies for improvement

    Blind source separation exploiting higher-order frequency dependencies

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    Blind source separation (BSS) is a challenging problem in real-world environments where sources are time delayed and convolved. The problem becomes more difficult in very reverberant conditions, with an increasing number of sources, and geometric configurations of the sources such that finding directionality is not sufficient for source separation. In this paper, we propose a new algorithm that exploits higher order frequency dependencies of source signals in order to separate them when they are mixed. In the frequency domain, this formulation assumes that dependencies exist between frequency bins instead of defining independence for each frequency bin. In this manner, we can avoid the well-known frequency permutation problem. To derive the learning algorithm, we define a cost function, which is an extension of mutual information between multivariate random variables. By introducing a source prior that models the inherent frequency dependencies, we obtain a simple form of a multivariate score function. In experiments, we generate simulated data with various kinds of sources in various environments. We evaluate the performances and compare it with other well-known algorithms. The results show the proposed algorithm outperforms the others in most cases. The algorithm is also able to accurately recover six sources with six microphones. In this case, we can obtain about 16-dB signal-to-interference ratio (SIR) improvement. Similar performance is observed in real conference room recordings with three human speakers reading sentences and one loudspeaker playing music

    Induction of apoptosis in HT-29 colon cancer cells by phloretin

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    Phloretin, which is present in apples and pears, has been found to inhibit the growth of several cancer cells and induce apoptosis of B16 melanoma and HL60 human leukemia cells. The present study examined whether and how phloretin induces apoptosis of HT-29 human colon cancer cells. Phloretin (0-100 mu mol/L) substantially decreased viable cell number and induced apoptosis of HT-29 cells in a dose-dependent manner. Western blot analysis of total cell lysates revealed that phloretin increased the protein levels of Bax but had no effect on Bcl-2. In addition, phloretin induced cleavage of caspase-8, -9, -7, and -3 and poly(ADP-ribose) polymerase. Furthermore, phloretin increased the levels of cytochrome c and Smac/Diablo in the cytosol. The present results indicate that phloretin inhibits HT-29 cell growth by inducing apoptosis, which may be mediated through changes in mitochondrial membrane permeability and activation of the caspase pathways.N

    Efeitos da administração sistêmica de 5-HT e 8-OH-DPAT sobre os estados de vigília e sono de pombos (Columba livia)

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    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em NeurociênciasInvestigar a participação dos mecanismos serotonérgicos sobre a regulação dos estados de sono e vigília em pombos por meio da caracterização comportamental e eletrográfica hipocampal dos estados de sono e vigília após administração sistêmica de 5-HT ou 8-OH-DPAT e quantificação dos efeitos da administração de 5-HT ou 8-OH-DPAT sobre a atividade eletrográfica hipocampal dos diferentes estados identificados

    Assessing young people’s learning needs related to sexuality and relationships on the Maltese Islands

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    This research explored young people’s learning needs related to sexuality and relationships withinthe current rapidly changing social, cultural and religious context of the Maltese Islands. It alsoexplored the challenges, opportunities and alternative means by which these needs can be met. Adefinitional matrix for needs assessment that adopts a sociological perspective to people’s needs,which is widely used in health promotion, was employed. This thesis was framed around theunderlying principles of youth involvement, participation and empowerment, and thus emphasisedyoung people’s own perspective of their learning needs.The mixed-methodology approach was adopted in this research. The first stage of investigationsought to achieve an overview of sexual behaviour and knowledge among young Maltese peopleaged 14 - 16 attending secondary schools. A stratified random sample of 1310 pupils (68% responserate) provided a first-ever snapshot of young people’s sexual behaviour in Malta. The second stagesought to explore young people’s felt and expressed learning needs within and outside the schoolsetting by way of sixteen focus groups involving another 166 pupils.Findings suggest a relatively low rate of pupils who would have practiced sexual intercourse byschool-leaving age in Malta (12.3%). Mean age at first intercourse seems similar to that of otherEuropean countries (14 years) for both genders. Only a fifth used condoms every time they had sex.Knowledge of STIs was scant. The pupils were more informed about HIV. Girls were moreknowledgeable. Boys had sex with more sexual partners. No gender differences were noted insubstance abuse with sex. Discussions among pupils revealed a high degree of perceived unmetlearning need. Participants valued highly learning about sexuality but thought it received much lessattention than their other academic learning needs. Disparities between schools were evidenced.Learning was sporadic and uncoordinated with conflicting messages from different teachers. Oftensessions started timely to pupils’ needs, but ended prematurely. Learning from parents was scantyand associated with the overall relationship and bonding between parents and the child. Gaps werenoted between perceived ideal sources (teachers, parents and visiting speakers) and actual /preferred sources (friends and the media). Needs were perceived in relation to the content andtiming of learning, sources of knowledge, learning styles and resources. Maltese pupils had diversevalues and called for a variety of approaches.Recommendations were made for a national sexuality education policy to standardize theframework of sexuality education among Maltese schools; more initial teacher training and inservicetraining in sexuality education to meet the needs of a diverse group of adolescents throughvarious approaches; more collaboration among teachers within schools; parenting skills and lifelonglearning opportunities for parents; more active involvement of adolescents and a widerconsultation with schools and families in the evaluation of sexuality education

    Calpains are involved in Entamoeba histolytica-induced death of HT-29 colonic epithelial cells

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    Entamoeba histolytica is an enteric tissue-invading protozoan parasite that can cause amebic colitis and liver abscess in humans. E. histolytica has the capability to kill colon epithelial cells in vitro; however, information regarding the role of calpain in colon cell death induced by ameba is limited. In this study, we investigated whether calpains are involved in the E. histolytica-induced cell death of HT-29 colonic epithelial cells. When HT-29 cells were co-incubated with E. histolytica, the propidium iodide stained dead cells markedly increased compared to that in HT-29 cells incubated with medium alone. This pro-death effect induced by ameba was effectively blocked by pretreatment of HT-29 cells with the calpain inhibitor, calpeptin. Moreover, knockdown of m- and µ-calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death. These results suggest that m- and µ-calpain may be involved in colon epithelial cell death induced by E. histolytica.ope
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