Mechanisms of blunted muscle vasodilation during peripheral chemoreceptor stimulation in heart failure patients

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement

Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats

Mezzarane RA, Kohn AF, Couto-Roldan E, Martinez L, Flores A, Manjarrez E. Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats. J Neurophysiol 108: 1176-1185, 2012. First published June 6, 2012; doi:10.1152/jn.00831.2011.-Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L 7 ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.

Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats

Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n = 8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (alpha-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11 +/- 0.49 vs. 5 +/- 0.3 mm Hg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8 +/- 0.26 vs. 5.02 +/- 0.21 mm Hg) and RV (5.1 +/- 0.21 vs. 4.2 +/- 0.12 mm Hg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (similar to 6-fold) and III (similar to 5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased a-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage. (C) 2011 Elsevier B.V. All rights reserved.

Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

The lateral septal area (LSA) is a limbic structure involved in autonomic, neuroendocrine and behavioural responses. An inhibitory influence of the LSA on baroreflex activity has been reported; however, the local neurotransmitter involved in this modulation is still unclear. In the present study, we verified the involvement of local LSA adrenoceptors in modulating cardiac baroreflex activity in unanaesthetized rats. Bilateral microinjection of the selective a1-adrenoceptor antagonist WB4101 (10 nmol in a volume of 100 nl) into the LSA decreased baroreflex bradycardia evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Nevertheless, bilateral administration of the selective a2-adrenoceptor antagonist RX821002 (10 nmol in 100 nl) increased baroreflex tachycardia without affecting reflex bradycardia. Treatment of the LSA with a cocktail containing WB4101 and RX821002 decreased baroreflex bradycardia and increased reflex tachycardia. The non-selective beta-adrenoceptor antagonist propranolol (10 nmol in 100 nl) did not affect either reflex bradycardia or tachycardia. Microinjection of noradrenaline into the LSA increased reflex bradycardia and decreased the baroreflex tachycardic response, an opposite effect compared with those observed after double blockade of a1- and a2-adrenoceptors, and this effect of noradrenaline was blocked by local LSA pretreatment with the cocktail containing WB4101 and RX821002. The present results provide advances in our understanding of the baroreflex neural circuitry. Taken together, data suggest that local LSA a1- and a2-adrenoceptors modulate baroreflex control of heart rate differently. Data indicate that LSA a1-adrenoceptors exert a facilitatory modulation on baroreflex bradycardia, whereas local a2-adrenoceptors exert an inhibitory modulation on reflex tachycardia.

Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats

Stern JE, Sonner PM, Son SJ, Silva FC, Jackson K, Michelini LC. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats. J Neurophysiol 107: 2912-2921, 2012. First published February 22, 2012; doi:10.1152/jn.00884.2011.-Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na+ spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

Baroreceptor-mediated activation of sympathetic nerve activity to salivary glands

Salivary gland function is regulated by both the sympathetic and parasympathetic nervous systems. Previously we showed that the basal sympathetic outflow to the salivary glands (SNA(SG)) was higher in hypertensive compared to normotensive rats and that diabetes reduced SNA(SG) discharge at both strains. In the present study we sought to investigate how SNA(SG) might be modulated by acute changes in the arterial pressure and whether baroreceptors play a functional role upon this modulation. To this end, we measured blood pressure and SNA(SG) discharge in Wistar-Kyoto rats (WRY-intact) and in WRY submitted to sinoaortic denervation (WRY-SAD). We made the following three major observations: (i) in WRY-intact rats, baroreceptor loading in response to intravenous infusion of the phenylephrine evoked an increase in SNA(SG) spike frequency (81%, p<0.01) accompanying the increase mean arterial pressure ((sic)MAP: +77 +/- 14 mmHg); (ii) baroreceptor unloading with sodium nitroprusside infusion elicited a decrease in SNA(SG) spike frequency (17%, p<0.01) in parallel with the fall in arterial blood pressure ((sic)MAP: 30 3 mmHg) in WRY-intact rats; iii) in the WRY-SAD rats, phenylephrine-evoked rises in the arterial pressure ((sic)MAP: +56 +/- 6 mmHg) failed to produce significant changes in the SNA(SG) spike frequency. Taken together, these data show that SNA(SG) increases in parallel with pharmacological-induced pressor response in a baroreceptor dependent way in anaesthetised rats. Considering the key role of SNA(SG) in salivary secretion, this mechanism, which differs from the classic cardiac baroreflex feedback loop, strongly suggests that baroreceptor signalling plays a decisive role in the regulation of salivary gland function. (C) 2012 Elsevier Inc. All rights reserved.

Reflexões sobre o desenvolvimento territorial sustentável, gestão social e cidadania deliberativa: o caso da bacia do rio Almada (BA)

Este artigo tem por objetivo discutir o desenvolvimento territorial sustentável a partir da atuação de diferentes atores sob a ótica da gestão social e o processo de cidadania deliberativa. Analisa-se a construção do "Programa de Manejo Agroambiental da Bacia do Rio Almada" na região pertencente ao território de cidadania Litoral Sul da Bahia. Organizaram-se os dados, as informações e as entrevistas por meio de estudo de caso. Para construção do caso, foi utilizada a triangulação de técnicas da história oral e do sensemaking. O caso em tela contribui para a reflexão sobre os desafios e oportunidades referentes à gestão social, indicando que o processo de cidadania deliberativa pode se constituir em estratégia necessária para o desenvolvimento territorial sustentável. Assim, fica claro que o diálogo, a participação dos atores na elaboração e implantação de políticas públicas é algo complexo, porém imprescindível, quando se almejam transformações das realidades sociais.

Reflexões sobre a influência de Maquiavel na educação e na formação do Estado Moderno

Este texto tem como objetivo analisar algumas formulações de Nicolau Maquiavel sobre a teoria política, bem como refletir sobre a contribuição de suas ideias, expostas na obra O Príncipe, para a formação do Estado Moderno Absoluto. Essa obra foi resultado de suas reflexões sobre os problemas do seu tempo: séculos XV e XVI, na Itália. O Príncipe expressava o desenvolvimento dos Estados Nacionais, a dessacralização do político, a independência do poder temporal em relação ao poder religioso e a primazia do Estado frente à religião. Consideramos que a obra de Maquiavel é de suma relevância para a história das ideias, principalmente, no campo da ciência política. Dessa forma, destacamos a importância do estudo de seu pensamento sob a perspectiva da Educação, o qual nos possibilita a compreensão dos fundamentos políticos da modernidade e, por conseguinte, o entendimento da formação do homem político-moderno.

Educação Física e qualidade de vida: reflexões e perspectivas

O estudo da qualidade de vida dos indivíduos se tornou um tema de destaque para a sociedade contemporânea. Todavia, pesquisas envolvendo a qualidade de vida devem considerar que esse é um tema complexo, que envolve aspectos objetivos e subjetivos, condições e estilos de vida, bemcomo fatores multidimensionais. Há uma ideia amplamente difundida na sociedade de que a atividade física, o exercício físico, práticas esportivas e atividades correlatas podem ter um impacto positivo na melhoria da qualidade de vida da população. Contudo, em vários estudos esta relação é analisada sob o ponto de vista biológico, no qual são considerados apenas os indicadores de saúde. Tais práticas são objetos de estudo da área de Educação Física nas mais diversas perspectivas, como a biológica, psicológica, social e cultural. Portanto, a Educação Física deve procurar produzir conhecimentos que respeitem os preceitos científicos e procurar evidências que efetivamente esclareçam a dinâmica dessa relação. Nesse sentido, o rigor metodológico, particularmente a definição conceitual, é fundamental para que haja melhor compreensão dos resultados obtidos e quais as generalizações efetivamente prováveis. Faz-se necessário ainda identificar as possibilidades e limitações de avaliações quantitativas, qualitativas e possíveis combinações.

Reflexões sobre desenvolvimento humano e neuropsicologia na obra de Vigotski

O presente texto configura-se como um ensaio teórico acerca do tema desenvolvimento humano na obra de Lev Vigotski, bem como das implicações desse tema para a Neuropsicologia na obra de Alexander Luria. O trabalho foi feito com base nas obras completas em espanhol de Vigotski e nas obras em português de Vigotski e de Luria. Foram eleitos como focos de investigação considerações acerca do funcionamento cerebral humano, do conceito de compensação, dos estudos sobre deficiência e do conceito de Sistema Funcional Complexo. Apesar de os inúmeros estudos e diferentes traduções da obra de Vigotski terem ampla divulgação e repercussão, principalmente nos campos da Psicologia e da Educação, questões concernentes à Neuropsicologia não têm tido igual relevância. Em vista disto este texto procura realçar as contribuições e a fecundidade da obra no que se refere à originalidade das ideias do autor acerca dos estudos da Neuropsicologia e do desenvolvimento humano.

Psicologia na atenção primária: ações e reflexões em programa de aprimoramento profissional

A inserção da Psicologia na Atenção Primária exigiu dos profissionais um repensar de suas práticas, ações e condutas, considerando a realidade da população com que se pretende atuar e os objetivos desse nível de atenção. O objetivo deste estudo é retratar a experiência de psicólogos do Programa de Aprimoramento Profissional em Promoção de Saúde na Comunidade em Núcleos de Saúde da Família em Ribeirão Preto, SP. Para o desenvolvimento das intervenções, inicialmente foram realizadas análises das necessidades, a fim de se verificar os padrões de morbimortalidade da população. A atuação dos psicólogos foi dividida em duas frentes de trabalho: uma voltada para o suporte à equipe e outra para realizar ações com a comunidade. Com os usuários, o psicólogo realizou visitas domiciliares, atendimentos individuais, familiares e coordenação de grupos. Os grupos eram abertos ou fechados, podendo ser classificados em educativos/reflexivos e de socialização. Para auxiliar no desenvolvimento das atividades, foram utilizados recursos audiovisuais, técnicas de dinâmica de grupo, discussões em grupos e trocas de experiências. Notase a importância de as ações do psicólogo na Atenção Básica estarem focadas na interferência nos fatores de risco à saúde da população, visando a alcançar mudanças comportamentais que proporcionem melhor qualidade de vida.

O ensino libertário e a relação entre trabalho e educação: algumas reflexões

Um dos principais desafios nos estudos a respeito da pedagogia escolar anarquista consiste, precisamente, em apreender os conteúdos de ensino. Com essa preocupação, este texto tem triplo objetivo: analisar a proposta educativa da instituição a cargo do professor libertário João Penteado, em São Paulo, nas primeiras décadas do século XX; indicar aspectos considerados relevantes relacionados à concepção de educação integral e à forma como o trabalho está presente na organização do ensino; e, por fim, apresentar alguns apontamentos de pesquisa que possam contribuir para sua continuidade e seu aprofundamento. Optou-se por abarcar período relativo a dois momentos de existência da escola dirigida por João Penteado - a Escola Moderna Nº 1 (1912-1919) e a Escola Nova (1920-1923). Entende-se que a cronologia definida consegue abranger a pluralidade de práticas escolares necessárias aos propósitos da análise. A documentação utilizada limita-se basicamente a jornais e demais fontes produzidas e/ou acumuladas nos diferentes períodos de existência da(s) escola(s), em particular, os jornais Boletim da Escola Moderna, Boletim da Escola Nova, Boletim da Academia Saldanha Marinho, O Início, O Iris. No estudo do primeiro período, que coincide com o da Escola Moderna, são também utilizadas notícias publicadas por alguns jornais da imprensa operária e anarquista, como A Lanterna, A Vida e O Amigo do Povo, entre outros.

Reflexões sobre a formação do acervo da Academia de Direito do Largo de São Francisco: do século XIX aos nossos dias

O trabalho apresenta algumas reflexões sobre a história da formação do acervo acadêmico dos cursos jurídicos do Brasil criados no século XIX, especificamente da Faculdade de Direito da Universidade de São Paulo. A primeira Biblioteca Pública de São Paulo, fundada em 1825, exerceu forte influência para que o Convento dos frades franciscanos recebesse a escola de direito criada por Decreto Imperial, em razão de seu fundo bibliográfico de 5.000 mil livros, preponderantemente de cunho eclesiástico, e considerável para os padrões culturais do Brasil à época. Atualmente configura-se como uma importante biblioteca jurídica acadêmica da América Latina e, ao longo da sua história tem sido uma instituição de depósito moral, isto é, recebe doações das mais diversas localidades do país, encaminhadas espontaneamente pelos autores para ter sua obra disponibilizada no acervo do primeiro e um dos mais tradicionais cursos de Direito do Brasil. Atualmente, este acervo está estimado em aproximadamente 400 mil itens, com doações de personalidades brasileiras. Outro ponto estudado refere-se ao estabelecimento de critérios para seleção de material – corpo editorial, autores de renome, relevância nos temas abordados etc. – em razão do boom editorial ocorrido na década de 1990, concomitante com o aumento de escolas de Direito no país. Chama-se à reflexão de quem atua na seara jurídica para atentar a pontos relevantes no momento da seleção para não incorrer no erro de avaliar com preconceito, modernidade, ideológico, interesse de estudo pessoal ou embasado apenas na data de publicação da obra. As ciências humanas, diferentemente de outras áreas, têm sua obsolescência mais lenta ou inexistente, decorrendo em grave erro para o Direito julgar exclusivamente pela data de publicação, o que torna premente aos profissionais bibliotecários dominarem conceitos básicos na área de atuação para que as bibliotecas sejam depositárias de material bibliográfico de qualidade.

Comparative genomic sequencing analysis of a region in human chromosome 11p15.3, mouse chromosome 7 and analysis of the novel STK33, Stk33 gene

The comparative genomic sequence analysis of a region in human chromosome 11p15.3 and its homologous segment in mouse chromosome 7 between ST5 and LMO1 genes has been performed. 158,201 bases were sequenced in the mouse and compared with the syntenic region in human, partially available in the public databases. The analysed region exhibits the typical eukaryotic genomic structure and compared with the close neighbouring regions, strikingly reflexes the mosaic pattern distribution of (G+C) and repeats content despites its relative short size. Within this region the novel gene STK33 was discovered (Stk33 in the mouse), that codes for a serine/threonine kinase. The finding of this gene constitutes an excellent example of the strength of the comparative sequencing approach. Poor gene-predictions in the mouse genomic sequence were corrected and improved by the comparison with the unordered data from the human genomic sequence publicly available. Phylogenetical analysis suggests that STK33 belongs to the calcium/calmodulin-dependent protein kinases group and seems to be a novelty in the chordate lineage. The gene, as a whole, seems to evolve under purifying selection whereas some regions appear to be under strong positive selection. Both human and mouse versions of serine/threonine kinase 33, consists of seventeen exons highly conserved in the coding regions, particularly in those coding for the core protein kinase domain. Also the exon/intron structure in the coding regions of the gene is conserved between human and mouse. The existence and functionality of the gene is supported by the presence of entries in the EST databases and was in vivo fully confirmed by isolating specific transcripts from human uterus total RNA and from several mouse tissues. Strong evidence for alternative splicing was found, which may result in tissue-specific starting points of transcription and in some extent, different protein N-termini. RT-PCR and hybridisation experiments suggest that STK33/Stk33 is differentially expressed in a few tissues and in relative low levels. STK33 has been shown to be reproducibly down-regulated in tumor tissues, particularly in ovarian tumors. RNA in-situ hybridisation experiments using mouse Stk33-specific probes showed expression in dividing cells from lung and germinal epithelium and possibly also in macrophages from kidney and lungs. Preliminary experimentation with antibodies designed in this work, performed in parallel to the preparation of this manuscript, seems to confirm this expression pattern. The fact that the chromosomal region 11p15 in which STK33 is located may be associated with several human diseases including tumor development, suggest further investigation is necessary to establish the role of STK33 in human health.

Relationship between pain and anxiety in rats

Clinically, it is well known that neuropathic pain often induces comorbid symptoms such as anxiety. In turn, also anxiety has been associated with a heightened experience of pain. Although, the link between pain and anxiety is well recognized in humans, the neurobiological basis of this relationship remains unclear. Therefore, the aim of the current study was to investigate the influence of neuropathic pain on anxiety and vice versa in rats by assessing not only pain-related behaviour but also by discovering possible key substrates which are responsible for the interrelation of pain and anxiety.rnIn rats with a chronic constriction of the sciatic nerve (CCI model) anxiety-like behaviour was observed. Since anxiety behaviour could be completely abolished after the treatment of the pure analgesic drugs gabapentin and morphine, we concluded that anxiety was caused by the strong persistent pain. Furthermore, we found that the neuropeptides oxytocin and vasopressin were upregulated in the amygdala of CCI rats, and the intra-amygdala treatment of an oxytocin antagonist but not the vasopressin antagonist could reduce anxiety-like behaviour in these animals, while no effect on mechanical hypersensitivity was observed. These data indicate that oxytocin is implicated in the underlying neuronal processes of pain-induced anxiety and helps to elucidate the pathophysiological mechanisms of neuropathic pain. rnTo assess the influence of trait anxiety on pain sensation in rats, we determined mechanical hypersensitivity after sciatic nerve lesion (CCI) in animals selectively bred for high anxiety or low anxiety behaviour. The paw withdrawal thresholds were significantly decreased in high anxiety animals in comparison to low anxiety animals 2 and 3 weeks after surgery. In a second model state anxiety was induced by the sub-chronic injection of the anxiogenic drug pentylentetrazol in naive rats. Pain response to mechanical stimuli was increased after pharmacologically-induced anxiety. These results provided evidence for the influence of both trait and state anxiety on pain sensation. rnThe studies contribute to the elucidation of the relationship between pain and anxiety. We investigated that the neuropathic pain model displays sensory as well as emotional factors of peripheral neuropathy. Changes in expression levels of neuropeptides in the central nervous system due to neuropathic pain may contribute to the pathophysiology of neuropathic pain and its related symptoms in animals which might also be relevant for human scenarios. The results of the current study also confirm that anxiety plays an important role in the perception of pain. rnA better understanding of pain behaviour in animals might improve the preclinical profiling of analgesic drugs during development. The study highlights the potential use of the rat model as a new preclinical tool to further investigate the link between pain and anxiety by determining not only the sensory reflexes after painful stimuli but also the more complex pain-related behaviour such as anxiety.rn