Receptores metabotrópicos de glutamato e sua relação com a Esclerose Lateral Amiotrófica (ELA) / Glutamate metabotropic receptors and its relationship with Amiotrophic Lateral Sclerosis (ALS)

A Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa fatal, que afeta neurônios motores superiores e inferiores, tem como fisiopatologia mais aceita a excitotoxicidade mediada por glutamato. O atual estudo tem como objetivo estabelecer a relação entre esse neurotransmissor e a ELA, a partir de uma revisão de literatura nas bases de dados Pubmed e Medline. O glutamato é o principal neurotransmissor do Sistema Nervoso Central (SNC) e a excitotoxicidade gerada pelo seu acúmulo nas fendas sinápticas é tida como um dos principais mecanismos envolvidos na fisiopatologia da ELA. Os indivíduos afetados pela ELA apresentam diminuição da expressão de determinados grupos de receptores metabotrópicos de glutamato (mGlu) nos neurônios e nas células da glia desses pacientes. Os mGlu possuem um papel de destaque na modulação da excitotoxicidade por glutamato e são subdivididos em três grupos. Os mGlus do grupo 1 amplificam as transmissões sinápticas excitatórias rápidas, e os dos grupos 2 e 3 atuam como neuroprotetores inibindo a liberação do glutamato na fenda sináptica. Os mGlus são, portanto, considerados alvos terapêuticos para a atuação de drogas que combatem a excitotoxicidade e induzem a produção de fatores neurotróficos, constituindo importante atuação no combate à ELA.

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease that affects upper and lower motor neurons, has as the most accepted pathophysiology the glutamate-mediated excitotoxicity. The present study aims to establish the relationship between this neurotransmitter and ALS, based on a literature review in the PubMed and Medline databases. Glutamate is the main neurotransmitter of the central nervous system (CNS) and the excitotoxicity generated by its accumulation in the synaptic clefts is considered one of the main mechanisms involved in the pathophysiology of ALS. People affected by ALS present a decrease in expression of certain metabotropic glutamate receptor (mGlu) groups in neurons and glial cells of these patients. mGlu has a prominent role in modulating glutamate excitotoxicity and are subdivided into three groups. Group 1 mGlu amplifies rapid excitatory synaptic transmissions, while groups 2 and 3 act as neuroprotective agents, since among other functions they inhibit glutamate release into the synaptic cleft. Finally, mGlu are considered therapeutic targets for the action of drugs that fight excitotoxicity and induce the production of neurotrophic factors, constituting an important action in the fight against ALS.

[New childbirth practices and the challenges for the humanization of health care in southern and southeastern Brazil]. / Novas práticas de atenção ao parto e os desafios para a humanização da assistência nas regiões sul e sudeste do Brasil.

The humanization of care in childbirth and the choice of performing cesarean or vaginal delivery have long been discussed in Brazil and worldwide. The complexities of the factors surrounding this issue range from the quality of obstetric care through to the significance of childbirth for women. A new proposal for humanization of delivery was introduced by the Brazilian Ministry of Health, the objectives of which were to make changes to the current system of delivery practices regarding, access, care, quality and resolution, in order to make it a more human and less technical experience. The Sofia Feldman Hospital, in Belo Horizonte - MG, is a benchmark in the adoption of best practices in care during childbirth, according to the Brazilian National Health Agency. However, for the humanization to become a national reality, there are still many challenges to be overcome within the public health system and the private partnerships. The most important problems are related with the current education system that continues to prepare health professionals to act in an interventional way, focused on the physician figure. This study aims to provide an overview about the different humanized care practices focused on pregnancy and childbirth, conducted in southern and southeastern Brazil.

Os diferentes modelos de assistência ao parto e a escolha pela realização de cesáreas ou parto vaginal há tempos são debatidos no Brasil e no mundo. A complexidade dos fatores que cercam o tipo de parto escolhido e sua assistência tem suscitado questionamentos que vão desde a qualidade da atenção obstétrica até o significado da parturição para as mulheres. Assim, a nova proposta do Ministério da Saúde (MS), de humanização na atenção ao parto estabelecendo mudanças em relação ao acesso, assistência, qualidade e resolutividade, tem por objetivo tornar a experiência da gestação mais humanizada e menos tecnicista. O Hospital Sofia Feldman, em Belo Horizonte (MG), é tido como referência pelas boas práticas nessa área, de acordo com a Agência Nacional de Saúde Suplementar. Para que a humanização do cuidado gestacional se torne uma realidade nacional ainda existem muitos desafios a serem superados dentro dos sistemas de saúde, como problemas, sobretudo quanto ao sistema de formação educacional, o qual continua a preparar profissionais de saúde dentro do modelo intervencionista, focado na figura do médico. O presente estudo tem por objetivo fornecer um panorama acerca das diferentes práticas assistenciais humanizadas, voltadas à gestação e ao parto, realizadas nas regiões sul e sudeste do Brasil.

Novas práticas de atenção ao parto e os desafios para a humanização da assistência nas regiões sul e sudeste do Brasil / New childbirth practices and the challenges for the humanization of health care in southern and southeastern Brazil

Resumo Os diferentes modelos de assistência ao parto e a escolha pela realização de cesáreas ou parto vaginal há tempos são debatidos no Brasil e no mundo. A complexidade dos fatores que cercam o tipo de parto escolhido e sua assistência tem suscitado questionamentos que vão desde a qualidade da atenção obstétrica até o significado da parturição para as mulheres. Assim, a nova proposta do Ministério da Saúde (MS), de humanização na atenção ao parto estabelecendo mudanças em relação ao acesso, assistência, qualidade e resolutividade, tem por objetivo tornar a experiência da gestação mais humanizada e menos tecnicista. O Hospital Sofia Feldman, em Belo Horizonte (MG), é tido como referência pelas boas práticas nessa área, de acordo com a Agência Nacional de Saúde Suplementar. Para que a humanização do cuidado gestacional se torne uma realidade nacional ainda existem muitos desafios a serem superados dentro dos sistemas de saúde, como problemas, sobretudo quanto ao sistema de formação educacional, o qual continua a preparar profissionais de saúde dentro do modelo intervencionista, focado na figura do médico. O presente estudo tem por objetivo fornecer um panorama acerca das diferentes práticas assistenciais humanizadas, voltadas à gestação e ao parto, realizadas nas regiões sul e sudeste do Brasil.

Abstract The humanization of care in childbirth and the choice of performing cesarean or vaginal delivery have long been discussed in Brazil and worldwide. The complexities of the factors surrounding this issue range from the quality of obstetric care through to the significance of childbirth for women. A new proposal for humanization of delivery was introduced by the Brazilian Ministry of Health, the objectives of which were to make changes to the current system of delivery practices regarding, access, care, quality and resolution, in order to make it a more human and less technical experience. The Sofia Feldman Hospital, in Belo Horizonte - MG, is a benchmark in the adoption of best practices in care during childbirth, according to the Brazilian National Health Agency. However, for the humanization to become a national reality, there are still many challenges to be overcome within the public health system and the private partnerships. The most important problems are related with the current education system that continues to prepare health professionals to act in an interventional way, focused on the physician figure. This study aims to provide an overview about the different humanized care practices focused on pregnancy and childbirth, conducted in southern and southeastern Brazil.

Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302).

The cardiovascular effects induced by labdane-302, a diterpene isolated from the stems of Xylopia langsdorffianna St. Hill and Tull, were evaluated in male Wistar rats. In normotensive, conscious animals, labdane-302 produced dose-dependent hypotension and tachycardia. These effects were significantly attenuated after pre-treatment with L-NAME (20 mg/kg, i.v.). In isolated mesenteric artery rings, labdane-302 (10(-10)-10(-4)M) elicited concentration-dependent relaxation of phenylephrine-induced contractions (IC50 = 5.4 +/- 1.4 microM). Endothelium removal, and pre-treatment with L-NAME (100 microM) or indomethacin (10 microM) caused significant reductions in sensitivity. Labdane-302 also caused concentration-dependent relaxation in arterial rings pre-contracted with high extracellular KCl (80 mM). In Ca2+-free depolarized preparations, labdane-302 inhibited contractions produced by cumulative increases in extracellular Ca2+ concentration. In GH3 cells, labdane-302 (100 microM) inhibited whole-cell L-type Ca2+ currents by approximately 50%. These results demonstrate that labdane-302 causes hypotension through peripheral vasodilation, mediated in part by NO and PGI2 and by blockade of Ca2+ entry through L-type Ca2+ channels.

N-salicyloyltryptamine, a new anticonvulsant drug, acts on voltage-dependent Na+, Ca2+, and K+ ion channels.

1. The aim of this work was to study the effects of N-salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage-gated ion channels in GH3 cells. 2. In this study, we show that STP at 17 microM inhibited up to 59.2+/-10.4% of the Ito and 73.1+/-8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K+ currents was dose-dependent (IC50=34.6+/-8.14 microM for Ito) and partially reversible after washing off. 3. Repeated stimulation at 1 Hz (STP at 17 microM) led to the total disappearance of Ito current, and an enhancement of IKD. 4. In the cell-attached configuration, application of STP to the bath increased the open probability of large-conductance Ca2+-activated K+ channels. 5. STP at 17 microM inhibited the L-type Ca2+ current by 54.9+/-7.50% without any significant changes in the voltage dependence. 6. STP at 170 microM inhibited the TTX-sensitive Na+ current by 22.1+/-2.41%. At a lower concentration (17 microM), no effect on INa was observed. 7. The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental 'in vivo' models.