Maria Cecília Puntel de Almeida

Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors.

An involvement of the transient receptor potential vanilloid (TRPV) 1 channel in the regulation of body temperature (Tb) has not been established decisively. To provide decisive evidence for such an involvement and determine its mechanisms were the aims of the present study. We synthesized a new TRPV1 antagonist, AMG0347 [(E)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide], and characterized it in vitro. We then found that this drug is the most potent TRPV1 antagonist known to increase Tb of rats and mice and showed (by using knock-out mice) that the entire hyperthermic effect of AMG0347 is TRPV1 dependent. AMG0347-induced hyperthermia was brought about by one or both of the two major autonomic cold-defense effector mechanisms (tail-skin vasoconstriction and/or thermogenesis), but it did not involve warmth-seeking behavior. The magnitude of the hyperthermic response depended on neither Tb nor tail-skin temperature at the time of AMG0347 administration, thus indicating that AMG0347-induced hyperthermia results from blockade of tonic TRPV1 activation by nonthermal factors. AMG0347 was no more effective in causing hyperthermia when administered into the brain (intracerebroventricularly) or spinal cord (intrathecally) than when given systemically (intravenously), which indicates a peripheral site of action. We then established that localized intra-abdominal desensitization of TRPV1 channels with intraperitoneal resiniferatoxin blocks the Tb response to systemic AMG0347; the extent of desensitization was determined by using a comprehensive battery of functional tests. We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on Tb.

Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock

Systemic inflammation is a leading cause of hospital death. Mild systemic inflammation is accompanied by warmth-seeking behavior (and fever), whereas severe inflammation is associated with cold-seeking behavior (and hypothermia). Both behaviors are adaptive. Which brain structures mediate which behavior is unknown. The involvement of hypothalamic structures, namely, the preoptic area (POA), paraventricular nucleus (PVH), or dorsomedial nucleus (DMH), in thermoregulatory behaviors associated with endotoxin (lipopolysaccharide [LPS])-induced systemic inflammation was studied in rats. The rats were allowed to select their thermal environment by freely moving in a thermogradient apparatus. A low intravenous dose of Escherichia coli LPS (10 µg/kg) caused warmth-seeking behavior, whereas a high, shock-inducing dose (5,000 µg/kg) caused cold-seeking behavior. Bilateral electrocoagulation of the PVH or DMH, but not of the POA, prevented this cold-seeking response. Lesioning the DMH with ibotenic acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage, also prevented LPS-induced cold-seeking behavior; lesioning the PVH with ibotenate did not affect it. Lesion of no structure affected cold-seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid-1 channel (“warmth receptor”). Nor did any lesion affect warmth-seeking behavior induced by a low dose of LPS, cold exposure, or pharmacological stimulation of the TRP melastatin-8 (“cold receptor”). We conclude that LPS-induced cold-seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH. These are the first two landmarks on the map of the circuitry of cold-seeking behavior associated with endotoxin shock.

Thermoregulatory Phenotype of the Trpv1 Knockout Mouse: Thermoeffector Dysbalance with Hyperkinesis

This study aimed at determining the thermoregulatory phenotype of mice lacking transient receptor potential vanilloid-1 (TRPV1) channels. We used Trpv1 knockout (KO) mice and their genetically unaltered littermates to study diurnal variations in deep body temperature (Tb) and thermoeffector activities under basal conditions, as well as thermoregulatory responses to severe heat and cold. Only subtle alterations were found in the basal Tb of Trpv1 KO mice or in their Tb responses to thermal challenges. The main thermoregulatory abnormality of Trpv1 KO mice was a different pattern of thermoeffectors used to regulate Tb. On the autonomic side, Trpv1 KO mice were hypometabolic (had a lower oxygen consumption) and hypervasoconstricted (had a lower tail skin temperature). In agreement with the enhanced skin vasoconstriction, Trpv1 KO mice had a higher thermoneutral zone. On the behavioral side, Trpv1 KO mice preferred a lower ambient temperature and expressed a higher locomotor activity. Experiments with pharmacological TRPV1 agonists (resiniferatoxin and anandamide) and a TRPV1 antagonist (AMG0347) confirmed that TRPV1 channels located outside the brain tonically inhibit locomotor activity. With age (observed for up to 14 months), the body mass of Trpv1 KO mice exceeded that of controls, sometimes approaching 60 g. In summary, Trpv1 KO mice possess a distinct thermoregulatory phenotype, which is coupled with a predisposition to age-associated overweight and includes hypometabolism, enhanced skin vasoconstriction, decreased thermopreferendum, and hyperkinesis. The latter may be one of the primary deficiencies in Trpv1 KO mice. We propose that TRPV1-mediated signals from the periphery tonically suppress the general locomotor activity.

O processo de trabalho da enfermagem em saúde coletiva e a interdisciplinaridade

This study aims at discussing and stimulating reflections on the need of an interdisciplinary dialogue when the object of work is the health-illness-care process. The authors discuss the definition of Nursing by considering its essence, care, its history and practice. Following, considerations about inter- and trans-disciplinary studies on collective health are presented and the authors conclude with a proposal of basing care on the theory of communicative action developed by Jurgen Habermas.This study aims at discussing and stimulating reflections on the need of an interdisciplinary dialogue when the object of work is the health-illness-care process. The authors discuss the definition of Nursing by considering its essence, care, its history and practice. Following, considerations about inter- and trans-disciplinary studies on collective health are presented and the authors conclude with a proposal of basing care on the theory of communicative action developed by Jürgen Habermas.

Promoção à saúde: trajetória histórica de suas concepções

This article is a literature review of the letters and declarations about the strategy of health promotion, since the Ottawa letter of 1986. Its objective is search for a historical restoration of their currents and conceptions in order to offer subsidies for understanding the present reality. This article concludes that the Ottawa letter continues to remain a central piece of direction for the health promotion strategy all over the world. It has oriented other conferences, principally when they emphasize social dimensions and the importance of five essential strategies for achieving full health: public policies, healthy environments, reinforcement of communitarian action, creation of personal abilities, and reorientation of health services. RESUMEN: Este artículo tiene como objetivo revisar la literatura de las cartas y las declaraciones sobre las estratégias de la promoción para la salud, a partir de la Carta de Ottawa-Ginebra en el año de 1986, se elabora un rescate histórico de sus corrientes y concepciones objetivando subsidios para poder comprenderlos actualmente. Se concluye que la Carta de Ottawa todavía permanece como una pieza fundamental en la estrategia de la promoción en la salud a nivel mundial. Ésta ha orientado todas las otras conferencias, principalmente, cuando se destaca la dimensión social y la importancia de las cinco estratégias fundamentales para poder alcanzarse una salud plena tales como: la política pública, el ambiente saludable, el refuerzo de la acción comunitaria, la creación de habilidades personales y la reorientación de los servicios de la salud. PALAVRAS-CHAVE: Saúde pública. Serviços de saúde. História.Este articulo tiene como objetivo revisar la literatura de las cartas y las declaraciones sobre las estrategias de la promocion para la salud, a partir de la Carta de Ottawa-Ginebra en el ano de 1986, se elabora un rescate historico de sus corrientes y concepciones objetivando subsidios para poder comprenderlos actualmente. Se concluye que la Carta de Ottawa todavia permanece como una pieza fundamental en la estrategia de la promocion en la salud a nivel mundial. Esta ha orientado todas las otras conferencias, principalmente, cuando se destaca la dimension social y la importancia de las cinco estrategias fundamentales para poder alcanzarse una salud plena tales como: la politica publica, el ambiente saludable, el refuerzo de la accion comunitaria, la creacion de habilidades personales y la reorientacion de los servicios de la salud.This article is a literature review of the letters and declarations about the strategy of health promotion, since the Ottawa letter of 1986. Its objective is search for a historical restoration of their currents and conceptions in order to offer subsidies for understanding the present reality. This article concludes that the Ottawa letter continues to remain a central piece of direction for the health promotion strategy all over the world. It has oriented other conferences, principally when they emphasize social dimensions and the importance of five essential strategies for achieving full health: public policies, healthy environments, reinforcement of communitarian action, creation of personal abilities, and reorientation of health services.

Thermoeffector neuronal pathways in fever: a study in rats showing a new role of the locus coeruleus

It is known that brain noradrenaline (norepinephrine) mediates fever, but the neuronal group involved is unknown. We studied the role of the major noradrenergic nucleus, the locus coeruleus (LC), in lipopolysaccharide (LPS)‐induced fever. Male Wistar rats had their LC completely ablated electrolytically or their catecholaminergic LC neurones selectively lesioned by microinjection of 6‐hydroxydopamine; the controls were sham‐operated. Both lesions resulted in a marked attenuation of LPS (1 or 10 μg kg−1, i.v.) fever at a subneutral (23°C) ambient temperature (Ta). Because electrolytic and chemical lesions produced similar effects, the role of the LC in fever was further investigated using electrolytic lesions only. The levels of prostaglandin (PG) E2, the terminal mediator of fever, were equally raised in the anteroventral third ventricular region of LC‐lesioned and sham‐operated rats during the course of LPS fever, indicating that LC neurones are not involved in febrigenic signalling to the brain. To investigate the potential involvement of the LC in an efferent thermoregulatory neuronal pathway, the thermoregulatory response to PGE2 (25 ng, i.c.v.) was studied at a subneutral (23°C, when fever is brought about by thermogenesis) or neutral (28°C, when fever is brought about by tail skin vasoconstriction) Ta. The PGE2‐induced increases in metabolic rate (an index of thermogenesis) and fever were attenuated in LC‐lesioned rats at 23°C, whereas PGE2‐induced skin vasoconstriction and fever normally developed in LC‐lesioned rats at 28°C. The LC‐lesioned rats had attenuated PGE2 thermogenesis despite the fact that they were fully capable of activating thermogenesis in response to noradrenaline and cold exposure. It is concluded that LC neurones are part of a neuronal network that is specifically activated by PGE2 to increase thermogenesis and produce fever.

Concepções da equipe de saúde da família sobre as visitas domiciliares

Connsidering home visits as a technology for interaction in family health care, this study aimed to understand how the Family Health team conceives these visits. A qualitative approach was used and data were collected through semistructured interviews. We interviewed nineteen professionals who belonged to two Family Health teams from an interior city in São Paulo. Results showed that visits are potential activities for more human and welcoming family care, with a view to bonding, confidence relations and getting to know users in the family environment. Visits are sometimes understood as health follow-up and sometimes as surveillance. Difficulties included reduced time availability and the teams impotence to act on problems.Entendendo as visitas domiciliares enquanto tecnologia de interacao no cuidado a saude da familia, o objetivo foi compreender as concepcoes da equipe de Saude da Familia sobre as visitas. Utilizou-se abordagem qualitativa e a entrevista semi-estruturada foi o instrumento de coleta de dados. Foram entrevistados dezenove profissionais de duas equipes de Saude de Familia de um municipio do interior paulista. Os resultados mostraram que as visitas sao atividades potenciais para o cuidado a familia, mais humano e acolhedor, permitindo o vinculo, lacos de confianca e conhecer o usuario no seu ambiente familiar. Apreende-se que as visitas ora sao compreendidas como acompanhamento da saude, ora como fiscalizacao. Dificuldades existiram como pouco tempo disponivel e impotencia da equipe frente aos problemas.

Tolerance to lipopolysaccharide is related to the nitric oxide pathway

Repeated administration of lipopolysaccharide (LPS) induces a refractory state to its usual pyrogenic effects which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) participates in the endotoxin tolerance. Single injection of LPS resulted in an elevation in body temperature (Tb), whereas a significant reduction of the thermoregulatory response to LPS was observed to repeated administration of LPS (administered at 48 h intervals). Intracerebroventricular (i.c.v.) injection of L-NAME (a non-selective NO inhibitor of nitric oxide synthesis) markedly enhanced the febrile response to LPS in tolerant rats. The data suggest that NO pathway in the central nervous system plays a role in endotoxin tolerance.

As tecnologias leves como geradoras de satisfação em usuários de uma unidade de saúde da família

O objetivo desta investigacao foi avaliar a qualidade da assistencia prestada em um nucleo de saude da familia (NSF), enfocando a satisfacao dos usuarios, com base nas tecnologias leves, bem como analisar aspectos dessa assistencia, produtores de satisfacao e de insatisfacao, no que diz respeito ao vinculo, a responsabilizacao, a resolubilidade, as expectativas, aos relacionamentos, ao conforto e acesso, e identificar recomendacoes para intervencoes locais. Apos realizarmos uma caracterizacao geral da populacao atendida no servico em estudo, selecionamos os sujeitos participantes da pesquisa. A coleta de dados deu-se por meio da entrevista semi-estruturada. A abordagem foi de natureza qualitativa, e os dados foram ordenados pelo metodo do Discurso do Sujeito Coletivo (DSC). A analise revela a importância atribuida, pelos usuarios do servico, as tecnologias leves, mas tambem a necessidade de diminuir o tempo de espera para as consultas e os encaminhamentos e obter o acesso a medicamentos e a atencao odontologica no proprio servico, fatores que levam a grande insatisfacao por parte dos usuarios.This study had the purpose to evaluate the quality of the health service provided at a Family Health Unit (FHU), with emphasis on user satisfaction, bas ed on soft technologies. Furthermore, this study also aimed to analyze the aspects of health care th at generated user satisfaction or dissatisfaction regarding attachment, accountability, providing sol utions, expectations, relationship, comfort, and access, and to identify recommendations for local i nterventions. The authors made a general characterization of the population seen at the stud ied service, and then selected the subjects. The

A pós-graduação na escola de enfermagem de Ribeirão Preto -- USP: evolução histórica e sua contribuição para o desenvolvimento da enfermagem

O trabalho objetiva fazer um resgate dos 25 anos da Pos-Graduacao da Escola de Enfermagem de Ribeirao Preto da Universidade de Sao Paulo, 1975-2000, atraves de reflexao critica sobre sua criacao e desenvolvimento. A metodologia baseou-se na analise quantitativa da producao da Pos-Graduacao (numero de alunos, docentes, dissertacoes e teses defendidas, tempo medio de duracao e outros) e em bibliografias sobre o assunto. Os resultados demonstram que a Pos-Graduacao se consolidou nos anos 90, criando os niveis de doutorado nos tres programas Enfermagem Psiquiatrica, Enfermagem Fundamental e Enfermagem em Saude Publica. Esse patamar alcancado aponta para a necessidade de projecao internacional.