Academic literature on the topic 'Icilin'

Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems likeXenopus laevesoocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off.

The transient receptor potential melastin-8 (TRPM8) channel is activated by the “cooling” compounds menthol and icilin. Pathophysiologically, it is implicated in the overactive bladder and bladder cooling reflex, but the activity of TRPM8 in normal bladder physiology is poorly understood. We investigated the distribution of TRPM8 channels and the effect of TRPM8 agonists on the contractile function of pig bladder (n = 35) strips and whole bladders. The distribution of TRPM8 was examined by immunohistochemistry. The effect of vesical or intravascular menthol (0.1–0.3 mmol/L) or icilin (50 μmol/L) on carbachol-induced isolated whole bladder contractions was monitored by recording vesical pressure. Strips of denuded detrusor or mucosa were mounted in organ baths to study the effect of TRPM8 agonists on the contractile responses to 10 μmol/L carbachol. TRPM8-like immunoreactivity was detected on pig urothelium. Intravascular menthol (0.3 mmol/L) and icilin (50 μmol/L) significantly decreased the magnitude of carbachol-induced whole bladder contraction, whereas vesical administration significantly increased the response. In detrusor and mucosal strips, both menthol (0.3 mmol/L) and icilin (50 μmol/L) inhibited carbachol-induced contractions. We conclude that the TRPM8 channel is expressed on the urothelium of pig bladder. In the whole organ, exposure of the urothelium to menthol or icilin increases the contractile response to carbachol. Where detrusor muscle is exposed directly to these compounds, the contractile response to carbachol is reduced.

AbstractAimsPain in response to innocuous cold stimulation (cold allodynia) is a common symptom in patients with neuropathic pain. Cold allodynia is difficult to treat and its mechanisms are poorly understood. Several transient receptor potential (TRP) channels have been shown to be the molecular sensors for cold stimulation in a temperature-dependent manner, but the contribution of various TRP channels in mediating cold allodynia in neuropathic pain is unclear. We have previously shown that spinally injured rats developed neuropathic pain-like behaviors, including marked cold allodynia. We now assessed the role of TRP channels in mediating cold allodynia in rats after ischemic spinal cord injury.Methods Methods: Spinal cord injury was produced using a photochemical method. The mechanical allodynia was assessed by examining the vocalization thresholds to graded mechanical touch/pressure applied with von Frey hairs. Temperature controlled cold stimulation was produced by a Peltier thermode (active surface 25 mm × 50 mm) connected to a MSA Thermal Simulator (Somedic, Sweden) with baseline temperature of 32 °C. The rate of temperature change was 0.5 °C/s. The temperature required to elicit cold allodynia was examined. The responses of the rats to topical application of icilin or menthol, agonists of transient receptor potential melastain 8 (TRPM8), were also studied.ResultsNormal rats did not exhibit nociceptive responses to cooling stimulation to the trunk and back area (minimal temperature +6°C) and they also did not react aversively to topical application of icilin or menthol. After spinal cord injury, the rats developed mechanical allodynia at the trunk and back just rostral to the dermatome of the injured spinal segments. In the same area, rats exhibited significant nociceptive responses to cooling from day 1 after injury, lasting for at least 70 days which is the longest time of observation. For the first two weeks after injury, the majority of spinally injured rats had a nociceptive response to cooling above 17°C. At day 70, about 50% of rats responded to cooling above 17 °C. Topical application of 400 μM icilin or 4mM menthol also elicited pain-like responses in spinally injured rats and these two cold mimetics also significantly exacerbated existing mechanical allodynia.ConclusionOur results showed that activation of the TRPM8 channel by menthol or icilin triggers allodynia in spinally injured rats and increases, rather than decreases, mechanical allodynia. TRPM8 channels which respond to cooling above 17 ° C may be involved at least in part in mediating cold allodynia in the rat model of neuropathic spinal cord injury pain.ImplicationsThe work introduced a method of quantitative testings of responses of rats to cold stimulation and may contribute to the understanding of mechanisms of cold allodynia after injury to the nervous system.

Background Migraine headache is a neurological disorder affecting millions worldwide. However, little is known about the mechanisms contributing to migraine. Recent genome-wide association studies have found single nucleotide polymorphisms in the gene encoding transient receptor potential channel M8. Transient receptor potential channel M8 is generally known as a cold receptor but it has been implicated in pain signaling and may play a role in migraine pain. Methods In order to investigate whether transient receptor potential channel M8 may contribute to the pain of migraine, the transient receptor potential channel M8 activator icilin was applied to the dura mater using a rat behavioral model of headache. Cutaneous allodynia was measured for 5 hours using Von Frey filaments. Results : Dural application of icilin produced cutaneous facial and hind paw allodynia that was attenuated by systemic pretreatment with the transient receptor potential channel M8-selective antagonist AMG1161 (10 mg/kg p.o.). Further, the anti-migraine agent sumatriptan (0.6 mg/kg s.c.) or the non-selective NOS inhibitor L-NAME (20 mg/kg i.p.) also attenuated allodynia when given as a pretreatment. Conclusions These data indicate that transient receptor potential channel M8 activation in the meninges produces behaviors in rats that are consistent with migraine and that are sensitive to pharmacological mechanisms known to have efficacy for migraine in humans. The findings suggest that activation of meningeal transient receptor potential channel M8 may contribute to the pain of migraine.

Thesis (Ph. D.)--West Virginia University, 2005.
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Doctor of Philosophy(PhD)
Two recently identified transient receptor potential (TRP) channels, TRPM8 and TRPA1, have been proposed to play an important role in mammalian cool and cold peripheral sensory transduction. When expressed in cell-lines the cloned TRPM8 and TRPA1 receptors have distinct pharmacological and temperature response characteristics. Although these receptors are also transported to the central terminals of primary afferents, little is known about their centrally mediated actions. In this thesis, I use an in vitro electrophysiological approach to investigate the dorsal horn processing of cool afferent modalities and the role of TRP ion channels. The results of this thesis provide further information on thermal processing, indicate direction for further research and suggest possible therapeutic targets for the management of abnormal cold sensory processing. Initial experiments demonstrate that the cooling agents and known TRPM8 and TRPA1 agonists, menthol and icilin, inhibit primary afferent evoked excitatory postsynaptic currents (EPSCs) in rat spinal cord dorsal horn neurons. In addition, temperature reduction, menthol and icilin increase the frequency of miniature EPSCs without affecting amplitude distribution or kinetics. Little or no direct postsynaptic effect on dorsal horn neurons, GABAergic or glycinergic transmission was found. In combination, these observations demonstrate that temperature reduction, menthol and icilin act presynaptically to increase the probability of glutamate release from primary afferent fibres. Further examination of the changes in glutamatergic synaptic transmission induced by temperature reduction, menthol and icilin reveals a subset of neurons sensitive to innocuous cool (< 29 oC) and low concentrations of icilin (3-10 µM) which closely match the temperature activation and pharmacological profile of TRPM8. In addition, the majority of lamina I and II neurons displayed characteristics partly consistent with TRPA1-activation, including a concentration-dependent response to icilin and blockade by ruthenium red. The present experiments did not allow thermal characterisation of these TRPA1-like responses. Together these observations indicate that the effects of menthol and icilin on glutamatergic synaptic transmission in the superficial dorsal horn are mediated by TRPM8 and possibly by TRPA1. Examination of the anatomical location of neurons activated by temperature reduction, menthol, icilin and capsaicin allowed the central termination pattern of thermoreceptive primary afferent fibres with specific TRP-like response characteristics to be determined. TRPM8-like presynaptic activation was confined to a subpopulation of neurons located in lamina I and outer lamina II, while the majority of neurons throughout laminae I and II received inputs sensitive to menthol, high concentrations of icilin and capsaicin. These findings suggest that innocuous cool sensation projects to a specific subpopulation of superficial dorsal horn neurons unlike other modalities (mediated by TRPV1, possibly TRPA1 and other receptors), which non-selectively engage circuits within the entire superficial dorsal horn. No morphological specificity was identified for recovered neurons after electrophysiological characterisation. Finally, mu-opioids were shown to inhibit basal glutamatergic synaptic transmission as well as menthol- and icilin-induced transmission in the superficial dorsal horn. Of particular interest, delta-opioids selectively inhibited icilin-induced synaptic transmission within the same location. The selective effect of delta-opioids suggests a possible role in modulating receptors activated by icilin (TRPM8 and TRPA1). Overall, this thesis provides further evidence that TRPM8 is responsible for the transduction of innocuous cold sensation in mammals and is a potential therapeutic target in humans with cold hyperaesthesia secondary to abnormal thermal processing. The use of delta-opioid agonists warrants further investigation in cold hypersensitivity states and potentially other forms of pain.

O contato físico precoce através do toque entre mãe e filho promove o desenvolvimento adequado da criança e constitui a génese da vinculação entre a díade. Contudo, quando o estado de saúde do recém-nascido obriga ao seu internamento na Unidade de Cuidados Intensivos Neonatais (UCIN), mãe e filho veem-se separados e obrigados a interagir num ambiente adverso, rodeados da mais diversa tecnologia, essencial para assegurar a sobrevivência do recém-nascido. Neste contexto, foi desenvolvida uma investigação que tem por objetivo compreender as experiências das mães quando tocam o filho internado numa UCIN tendo em vista definir diretrizes que promovam o toque e o envolvimento dos pais nos cuidados ao filho, no sentido de promover a interação mãe-filho e fomentar a autonomia na prestação de cuidados ao filho. Trata-se de um estudo exploratório, descritivo, de abordagem qualitativa e de inspiração fenomenológica. Foram realizadas entrevistas semiestruturadas a dez mães com recém-nascidos internados numa Unidade de Cuidados Intensivos Neonatais do Porto. A análise de dados foi realizada utilizando a técnica de análise de conteúdo de Bardin, tendo emergido três temas: definindo o tocar, compreendendo a complexidade do tocar e contextos que envolvem o tocar, com diversas categorias identificadas em cada tema. Os resultados desta investigação representam um contributo importante para o conhecimento e compreensão da vivência do toque materno numa UCIN, na identificação de estratégias que promovam o toque e o envolvimento dos pais nos cuidados ao filho, no sentido de possibilitar a implementação de intervenções de enfermagem que promovam a integração efetiva da mãe no ambiente da UCIN.

Diploma thesis called "Digital Generation. Involvement of Information and Communication Technology in Educational Process" is focused on the role of computers in a life of adolescents. Information and Communication Technology (ICT) is evolving very fast and transform our everyday life. The aims of the thesis are (1) to explore the change of "digital generation" in Czech society in the beginning of 21 century, (2) to find out if there is a correlation between playing computer games and school results and (3) to identify which factors influence computer literacy. In order to achieve those aims, the comparative secondary analysis of international researches of pupils PISA 2003, 2012 and research focused on computer and information literacy - ICILS 2013were used. The results suggest that between 2003 and 2013 digital possession and using of ICT by fifteen year old pupils increased, so digital generation Y and Z were identified in Czech society. Playing of computer games remains domain of boys. Computer and information literacy increases with experience with computers, self- esteem of basic computer skills and with a higher society status of parents. Better results in the test also achieve girls and pupils of grammar school. Keywords Generation, Information and Communication Technology, Education,...

Tese de doutoramento em Sociologia, na especialidade de Relações de Trabalho, Desigualdades Sociais e Sindicalismo, apresentada à Faculdade de Economia da Universidade de Coimbra
A desigualdade entre mulheres e homens é uma temática complexa e plena de atualidade, presente quer na agenda política internacional quer na investigação em ciências sociais. Além de um princípio e direito fundamental, a igualdade entre mulheres e homens tem vindo a ser encarada como uma forma de economia inteligente, capaz de contribuir, nomeadamente, para o aumento do bem-estar das populações e para o crescimento e o progresso dos países. No entanto, nos países da União Europeia (UE-28), as mulheres estão mais expostas a situações de desvantagem no mercado de trabalho (MT) do que os homens, apesar de constituírem sensivelmente metade da população, de terem mais êxito nos respetivos percursos escolares na generalidade dos Estados-Membros e de representarem a maioria dos diplomados do ensino superior. Mas então, se a igualdade promove a justiça e o crescimento económico, como tantas vezes se alega, como se explica que as desigualdades no MT sejam ainda, em pleno século XXI, um fenómeno persistente, inclusive nos países considerados dos mais desenvolvidos do mundo? Será que, no contexto da União Europeia, os países com menores desigualdades entre mulheres e homens no MT apresentam maiores níveis de rendimento, educação e saúde? E será que os países podem melhorar as suas realizações nessas áreas tornando a composição do seu MT mais equilibrada em termos de sexo? Considerando a performance como o grau de desempenho dos países no que à sua capacidade de alcançar certos fins valorizados pela sociedade diz respeito, seja em termos económicos, seja em termos sociais, esta tese tem dois objetivos principais: 1) desenvolver um novo indicador composto de igualdade laboral e 2) estudar a relação da igualdade entre mulheres e homens no mercado de trabalho com a performance dos países da UE-28. Para cumprir os objetivos propostos, numa primeira fase, são exploradas as razões que ajudam a explicar a existência e a persistência das desigualdades entre mulheres e homens no MT, num exercício que discute as principais correntes teóricas e que questiona a conceptualização e a operacionalização do fenómeno das desigualdades laborais. Depois, é estudada a inter-relação da igualdade com o crescimento e o desenvolvimento dos países, tendo em conta a literatura teórica e empírica produzida não só para o contexto dos países da UE, mas também para o contexto de outros países. Na UE, a igualdade entre mulheres e homens no MT é tida como um objetivo, uma meta e um princípio fundamental. No entanto, a sua valorização enquanto direito tem vindo a ceder lugar a uma abordagem integrada que coexiste com a proliferação de uma argumentação que enaltece os benefícios económicos da igualdade de ‘género’, subjugando-a, deste modo, a imperativos de crescimento económico e de eficiência. É no âmbito deste complexo processo, que acaba geralmente por priorizar determinados indicadores de desigualdade, que propomos um novo índice – o ICIL (Indicador Composto de Igualdade Laboral) – para medir de forma holística o nível de igualdade relativa nos países da UE-28 combinando, simultaneamente, indicadores relacionados com a participação no mercado de trabalho, chefia e liderança, salários e condições de trabalho. O ICIL, criado com base na técnica não paramétrica conhecida como Data Envelopment Analysis (DEA), permite também identificar os países que, pelos seus bons resultados, podem servir de referência para aprendizagem aos restantes. Usando dados do Eurostat, da Comissão Europeia e do Banco Mundial relativos ao período 2008-2013, os resultados revelam algumas transformações paradigmáticas que, em matéria de igualdade laboral, têm vindo a ocorrer ao longo dos últimos anos neste conjunto particular de países. A análise da situação da Letónia, país que em termos relativos apresenta os níveis mais elevados de igualdade laboral relativa desde 2010 e que o ICIL identifica como referência de aprendizagem para um número assinalável de países, permite uma reflexão profunda que, no global, vem chamar a atenção para a necessidade de, no contexto dos países tidos como económica e socialmente mais avançados, se (re)pensar o enquadramento da igualdade entre mulheres e homens no MT, nomeadamente no âmbito da estratégia e das políticas europeias, (re)orientando o enfoque do debate para uma abordagem que a priorize como uma das dimensões centrais do desenvolvimento humano. Os resultados deste estudo reforçam a ideia de que a igualdade entre mulheres e homens no MT é, ela própria, também indicativa do nível de desenvolvimento dos países e não deve ser menorizada nem encarada apenas como uma estratégia com potencial para estimular o crescimento económico. No contexto da UE-28, a riqueza dos países e o desenvolvimento social em termos de saúde e educação não são uma condição sine qua non para a obtenção de um maior equilíbrio laboral entre mulheres e homens nem para a concretização das metas e dos objetivos de igualdade.
Inequality between women and men is a complex and current issue, present both on the international political agenda and in research in the social sciences. In addition to a fundamental principle and right, equality between women and men has been seen as a form of intelligent economy capable of contributing in particular to the population welfare improvement and to the countries’ growth and progress. However, in the European Union countries (EU-28), women are more exposed to disadvantages in the labour market (LM) than men, although the former make up approximately half the population, they are more succeeded in academic background and they also represent the majority of higher education graduates in most Member States. So, if equality promotes justice and economic growth, as it is often claimed, how to explain that inequalities in the labour market are still a persistent phenomenon in the 21st century, even in countries considered to be the most developed in the world? In the context of the European Union, do the countries with the lowest inequality levels between women and men in the labour market have higher levels of income, education and health? And can countries improve their achievements in these areas by making the composition of their labour market more gender-balanced? Considering performance as the degree of achievement of countries in their ability to reach certain goals valued by society both economically and socially, this thesis has two main objectives: 1) to develop a new composite indicator of equality in labour and 2) to study the links between gender equality in the labour market and the performance of the EU-28 countries. For that purpose, the reasons that help to explain the existence and persistence of inequalities between women and men in the labour market are explored through an exercise that discusses the main theories and also questions the conceptualization and operationalization of the labour inequalities phenomenon. Then, the interrelation of (un)equality with the growth and development of the countries is analysed, taking into account the theoretical and empirical literature produced not only in the EU but also internationally. Gender equality in the LM is viewed as a goal and as a fundamental principle in the EU. However, its appreciation as a right has given way to an integrated approach that coexists with the proliferation of arguments that enhance the economic benefits of gender equality, thereby subjecting it to imperatives of economic growth and efficiency. It’s within the scope of this complex process, which usually ends up giving priority to certain indicators of inequality, that we propose a new index –CIEL (Composite Indicator for Equality in Labour) – to holistically measure the level of relative equality in the EU-28 countries, simultaneously combining indicators related to labour market participation, management and leadership, wages and working conditions. CIEL, established on the basis of a non-parametric technique known as Data Envelopment Analysis (DEA), also allows the identification of the benchmark countries. By using data from Eurostat, European Commission and World Bank for the period 2008-2013, the results reveal some paradigmatic transformations that have taken place over the last few years in this particular set of countries. The analysis of the situation in Latvia, which in relative terms has the highest levels of employment equality since 2010 and which CIEL identifies as a benchmark for a considerable number of countries, allows a deep reflection that draws attention to the need, in the context of the countries considered to be more developed economically and socially, to (re)think the framework of the equality between women and men on the LM, particularly in the scope of the European strategy and policies, (re)orientating the focus of the debate towards an approach that prioritises it as one of the key aspects of human development. The results of this study reinforce the idea that equality between women and men on the LM is also illustrative of the countries development level and should neither be narrowed nor viewed only as a strategy with potential to stimulate economic growth. In the context of the EU-28, the wealth of countries and the social development in terms of health and education are neither a sine qua non condition to achieve a better work-life balance between women and men nor to achieve the goals and objectives of equality.