Eucalyptol, an essential oil, reduces contractile activity in rat cardiac muscle

Eucalyptol is an essential oil that relaxes bronchial and vascular smooth muscle although its direct actions on isolated myocardium have not been reported. We investigated a putative negative inotropic effect of the oil on left ventricular papillary muscles from male Wistar rats weighing 250 to 300 g, as well as its effects on isometric force, rate of force development, time parameters, post-rest potentiation, positive inotropic interventions produced by Ca2+ and isoproterenol, and on tetanic tension. The effects of 0.3 mM eucalyptol on myosin ATPase activity were also investigated. Eucalyptol (0.003 to 0.3 mM) reduced isometric tension, the rate of force development and time parameters. The oil reduced the force developed by steady-state contractions (50% at 0.3 mM) but did not alter sarcoplasmic reticulum function or post-rest contractions and produced a progressive increase in relative potentiation. Increased extracellular Ca2+ concentration (0.62 to 5 mM) and isoproterenol (20 nM) administration counteracted the negative inotropic effects of the oil. The activity of the contractile machinery evaluated by tetanic force development was reduced by 30 to 50% but myosin ATPase activity was not affected by eucalyptol (0.3 mM), supporting the idea of a reduction of sarcolemmal Ca2+ influx. The present results suggest that eucalyptol depresses force development, probably acting as a calcium channel blocker.

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 ��M EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 ��g, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 ��g/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Effects of ouabain on vascular reactivity

Ouabain is an endogenous substance occurring in the plasma in the nanomolar range, that has been proposed to increase vascular resistance and induce hypertension. This substance acts on the a-subunit of Na+,K+-ATPase inhibiting the Na+-pump activity. In the vascular smooth muscle this effect leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+ exchanger and to an increased vascular tone. It was also suggested that circulating ouabain, even in the nanomolar range, sensitizes the vascular smooth muscle to vasopressor substances. We tested the latter hypothesis by studying the effects of ouabain in the micromolar and nanomolar range on phenylephrine (PE)-evoked pressor responses. The experiments were performed in normotensive and hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular beds. The results showed that ouabain pretreatment increased the vasopressor responses to PE in vitro and in vivo. This sensitization after ouabain treatment was also observed in hypertensive animals which presented an enhanced vasopressor response to PE in comparison to normotensive animals. It is suggested that ouabain at nanomolar concentrations can sensitize vascular smooth muscle to vasopressor stimuli possibly contributing to increased tone in hypertension.

Neural reflex regulation of arterial pressure in pathophysiological conditions : interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex

The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival. The objective of the present review was to provide information about the basic reflex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechano- and chemosensitive cardiopulmonary reflexes), and changes in blood-gas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood. There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model of arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

Indicadores de qualidade do solo e determina����o de n��veis de degrada����o de pastagens

A utiliza����o do solo no Brasil foi realizada de forma explorat��ria, com a convers��o de sistemas naturais em sistemas agr��colas extrativistas. Grande parte das ��reas de sistemas naturais deu lugar ��s ��reas de cultivo, posteriormente sucedidas por pastagens, encontrando-se boa parte em elevado est��gio de degrada����o. Diante do exposto, o presente trabalho tem como objetivo avaliar a sensibilidade de alguns atributos f��sicos, qu��micos, compartimentos da mat��ria org��nica e determina����es de campo como indicadores de qualidade do solo estabelecendo rela����es entre os mesmos. O estudo foi desenvolvido no munic��pio de Governador Valadares-MG, para tal foram escolhidos n��veis de pastagens progressivamente degradadas observadas visualmente (pastagem 1, pastagem 2, pastagem 3 e pastagem 4), duas ��reas de capoeira em est��gios de regenera����o natural (capoeira 1 e capoeira 2) e mata (refer��ncia). O solo em estudo foi um Argissolo Vermelho, textura argilosa. As determina����es dos indicadores f��sicos, qu��micos e compartimentos da mat��ria org��nica foram realizadas em quatro profundidades (0-5, 5-10, 10-20 e 20-40 cm). Foram realizadas tamb��m determina����es de campo, todos os atributos foram determinados no ter��o m��dio de uma pedoforma convexa, em dois per��odos, chuvoso e seco. Atrav��s dos atributos do solo utilizados como indicadores do solo, foi poss��vel separar dois n��veis de pastagens degradadas, baixa degrada����o (pastagem 1 e pastagem 2) e elevada degrada����o (pastagem 3 e pastagem 4). A melhor qualidade do solo foi observada na ��rea de mata. Entre os atributos do solo utilizados como indicadores de qualidade do solo os mais sens��veis aos n��veis de pastagens degradadas s��o os atributos qu��micos pH, Ca2+, Mg2+, Al3+, H+Al, satura����o por bases (V), satura����o por alum��nio (m), seguidos pelos atributos f��sicos macroporosidade e porosidade total. Os compartimentos da mat��ria org��nica do solo, mat��ria org��nica particulada (MOP), mat��ria org��nica leve (MOL) e carbono sol��vel em ��gua (CSA) utilizados como indicadores de qualidade do solo s��o eficientes em diferenciar a qualidade do solo nas convers��es de sistema, mata/pastagens e pastagens/capoeiras, n��o sendo sens��vel aos n��veis de pastagens degradadas, o que sugere estudos futuros utilizado compartimentos mais sens��veis a pequenas varia����es. As determina����es de campo espessura do horizonte ���A���, profundidade do sistema radicular e taxa de cobertura do solo s��o sens��veis aos n��veis de pastagens degradadas, e apresentam uma boa correla����o com os indicadores de laborat��rio macroporosidade (Ma), mat��ria org��nica particulada (MOP), satura����o por bases (V), satura����o por alum��nio (m) sugerindo assim a utiliza����o dessas determina����es como indicadores de qualidade do solo em pastagens degradadas, para o solo e a regi��o estudados.

Cristaliza����o de Biomateriais Vitrocer��micos e Mineraliza����o em Meio Fisiol��gico Simulado

We propose new theoretical models, which generalize the classical Avrami-Nakamura models. These models are suitable to describe the kinetics of nucleation and growth in transient regime, and/or with overlapping of nucleation and growth. Simulations and predictions were performed for lithium disilicate based on data reported in the literature. One re-examined the limitations of the models currently used to interpret DTA or DSC results, and to extract the relevant kinetic parameters. Glasses and glass-ceramics with molar formulation 0.45SiO2? (0.45-x)MgO?xK2O?0.1(3CaO.P2O5) (0?x?0.090) were prepared, crystallized and studied as potential materials for biomedical applications. Substitution of K+ for Mg2+ were used to prevent devritification on cooling, to adjust the kinetics of crystallization and to modify the in vitro behaviour of resulting biomaterials. The crystallization of the glass frits was studied by DTA, XRD and SEM. Exothermic peaks were detected corresponding to bulk crystallization of whitlockite-type phosphate, Ca9MgK(PO4)7, at approximately 900��C, and surface crystallization of a predominant forsterite phase (Mg2SiO4) at higher temperatures. XRD also revealed the presence of diopside (CaMgSi2O6 in some samples. The predominant microstructure of the phosphate phase is of the plate-type, seemingly crystallizing by a 2-dimensional growth mechanism. Impedance spectroscopy revealed significant changes in electrical behaviour, associated to crystallization of the phosphate phase. This showed that electrical measurements can be used to study the kinetics of crystallization for cases when DTA or DSC experiments reveal limitations, and to extract estimates of relevant parameters from the dependence of crystallization peak temperature, and its width at half height. In vitro studies of glasses and glass-ceramics in acelular SBF media showed bioactivity and the development of apatite layers The morphology, composition and adhesion of the apatite layer could be changed by substitution of Mg2+ by K+. Apatite layers were deposited on the surface of glass-ceramics of the nominal compositions with x=0 and 0.09, in contact with SBF at 37��C. The adhesion of the apatite layer was quantified by the scratch test technique, having been related with SBF?s immersion time, with composition and structure of the glass phase, and with the morphology of the crystalline phase of the glass-ceramics. The structure of three glasses (x=0, 0.045 and 0.090) were investigated by MAS-NMR ( 29Si and 31P), showing that the fraction of Q3 structural units increases with the contents of Mg, and that the structure of these glasses includes orthophosphate groups (PO43-) preferentially connected to Ca2+ ions. Mg2+ ions show preference towards the silicate network. Substitution of Mg2+ by K+ allowed one to change the bioactivity. FTIR data revealed octacalcium phosphate precipitation (Ca8H2(PO4)6.5H2O) in the glass without K, while the morphology of the layer acquires the shape of partially superimposed hemispheres, spread over the surface. The glasses with K present a layer of acicular hidroxyapatite, whose crystallinity and needles thickness tend to increase along with K content.

Freud com Dam��sio: Psican��lise e neurobiologia

Freud estava convencido que os desenvolvimentos futuros da Biologia iriam trazer respostas a algumas quest��es levantadas pela psican��lise; ao mesmo tempo, ele tinha medo que os tais desenvolvimentos pusessem a psican��lise em risco. Tanto a esperan��a nas possibilidades infinitas da biologia como o medo relativo ao futuro da psican��lise est��o descritos no artigo ���Para al��m do Princ��pio do Prazer���, escrito em 1920. A inten����o deste texto �� questionar, ao fim de tantos anos, a solidez das esperan��as e dos medos freudianos. Para conseguirmos atingir o nosso prop��sito, contamos com uma das mais extraordin��rias investiga����es do campo da neurobiologia, conduzida por Ant��nio Dam��sio e a sua equipa, nas ��ltimas d��cadas. Estas investiga����es n��o podem deixar a psican��lise indiferente. Tem que se confrontar a elas com novos desafios, questionar os resultados destas investiga����es se n��o quer perder a singularidade da sua teoria e pr��tica. Tencionamos, com esta comunica����o, trazer a nossa contribui����o para esta quest��o.

Avalia����o da prote����o conferida pela via de sinaliza����o do Nrf2 num modelo experimental de sobrecarga de ferro in vivo

O ferro �� encontrado em praticamente todos os seres vivos, sendo um cofator para prote��nas que desempenham fun����es essenciais �� vida. Nos mam��feros, a maioria do ferro est�� incorporada na hemoglobina ou armazenado no f��gado, ligado �� ferritina. �� absorvido pelos enter��citos, sendo a principal forma de controlo dos seus n��veis. A sobrecarga de ferro pode levar a hemocromatose, podendo ser t��xica para v��rios ��rg��os. O fator de transcri����o Nrf2 �� importante na ativa����o de genes citoprotetores em situa����es de stress oxidativo/eletrof��lico, colocando-se a hip��tese de que poder�� estar envolvido na resposta �� progress��o de doen��a devido �� sobrecarga de ferro. Com o objetivo de determinar se a via do Nrf2 representa uma prote����o contra a toxicidade do ferro a n��vel hep��tico, foram realizadas duas experi��ncias nas quais murganhos C57BL/6 (B6) e Nrf2-/- machos foram alimentados com dieta standard ou com dieta enriquecida em ferro carbonilo (FeC) (0,5% ou 2,0%). Os resultados demonstram sobrecarga de ferro nos animais que receberam dieta enriquecida, sendo que os que receberam FeC 2,0% apresentaram n��veis mais elevados de ferro hep��tico e s��rico, bem como da satura����o da transferrina. Os murganhos Nrf2-/- s��o mais suscet��veis a esta acumula����o, mostrando evid��ncias patol��gicas mais graves, nomeadamente necrose hepatoc��tica e infiltra����o de c��lulas inflamat��rias. A dele����o do Nrf2 associado a uma dieta suplementada com FeC 2,0% parece n��o ser suficiente para o desenvolvimento de fibrose hep��tica. O estudo da express��o de genes e prote��nas do metabolismo do ferro mostrou que os animais B6 e Nrf2-/- s��o igualmente capazes de responder �� sobrecarga de ferro, sugerindo que a sua diferente suscetibilidade �� toxicidade do ferro n��o se dever�� a uma regula����o ineficiente da homeostasia do Fe. A dieta com FeC 2,0% aumentou a express��o de dois genes alvo do Nrf2, Nqo1 e Gsta1, o que n��o se verificou com os genes e prote��nas GCLC e GCLM. A express��o de genes pr��-inflamat��rios n��o mostrou evid��ncias de inflama����o nestes animais. Foi demonstrado que os animais Nrf2-/- s��o mais suscet��veis �� toxicidade do ferro, concluindo-se que a via do Nrf2 �� ativada em resposta a uma dieta contendo quantidades excessivas de FeC e que confere prote����o contra a acumula����o de ferro em murganhos B6.

O papel da angiog��nese e da hem��lise na ��lcera de perna de pessoas com anemia falciforme

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

Efeitos da timectomia neonatal sobre o dimorfismo sexual esquel��tico e concentra����o plasm��tica de leptina em ratos

P��s-gradua����o em Ci��ncias Fisiol��gicas - FOA

Magnesium, insulin resistance and body composition in healthy postmenopausal women

Objective: This study was conducted to determine the association between magnesium (Mg), body composition and insulin resistance in 136 sedentary postmenopausal women, 50 to 77 years of age. Methods: Diabetics, hypertensives and women on hormonal replacement therapy were excluded and the remaining 74 were divided according to BMI���25 (obese: OG) and BMI<25 kg/m2 (non-obese: NOG). Nutritional data disclosed that intakes were high for protein and saturated fat, low for carbohydrates, polyunsaturated fat and Mg and normal for the other nutrients, according to recommended dietary allowances (RDA). Mg values in red blood cells (RBC-Mg) and plasma (P-Mg), were determined, as were fasting glucose, and insulin levels, Homeostasis Model Assessment (HOMA), body mass index (BMI), body fat percent (BF %), abdominal fat (AF) and free fat mass (FFM). Results: RBC-Mg values were low in both groups when compared with normal values. There were significant differences in body composition parameters, HOMA and insulin levels, with higher basal insulin levels in OG. RBC-Mg was directly correlated with insulin, HOMA and FFM in both groups, according to Pearson correlations. HOMA in OG was also directly correlated with BMI, FFM and AF. In NOG, HOMA was only correlated with FFM. The low RBC-Mg levels observed were probably due to low Mg intake and to deregulation of factors that control Mg homeostasis during menopause. Conclusions: Both Mg deficit and obesity may independently lead to a higher risk for insulin resistance and cardiovascular disease.

Desacyl-ghrelin does not influence insulin sensitivity

Acyl-ghrelin has been reported to increase food intake and adiposity and it is the best studied of the orexigenic gastrointestinal hormones. On the other hand, desacyl-ghrelin ��� DAG (the unacylated form of the hormone) has been reported as a potential player on carbohydrate metabolism. However, the potential impact of DAG on glucose homeostasis remains uncertain. In this study we aim to assess the association between DAG and insulin sensitivity.

���Papel dos recetores purin��rgicos no crescimento e temodela����o do tecido cavernoso���

A adenosina �� um nucle��sido ub��quo envolvido na regula����o de controlo do t��nus vascular do tecido cavernoso, desempenhando um papel importante na fisiopatologia da Disfun����o Er��til (DE) resistente aos f��rmacos relaxantes musculares cl��ssicos. Apesar da import��ncia comprovada dos recetores da adenosina na fisiopatologia da DE no homem, pouca informa����o �� conhecida no que diz respeito �� express��o e localiza����o dos recetores purin��rgicos no Tecido Cavernoso de Ratazana (TCR). Neste trabalho avaliou-se o fen��tipo dos recetores purin��rgicos respons��veis pela regula����o do t��nus do tecido er��til de ratazana por imunofluoresc��ncia indireta aplicada �� microscopia confocal em co-culturas de c��lulas endoteliais e musculares lisas do TCR. Para al��m da caracteriza����o imunofenot��pica, desenvolveu-se uma t��cnica que permite diferenciar funcionalmente em tempo real (por microscopia confocal funcional) c��lulas musculares lisas e c��lulas endoteliais isoladas de TCR em co-cultura marcadas com a sonda fluorescente Fluo-4NW. Esta t��cnica permite distinguir cada um dos subtipos celulares mediante o padr��o e a magnitude das oscila����es dos n��veis intracelulares de Ca2+ ([Ca2+]i) em resposta ao ATP (agonista P2) e �� fenilefrina (PE, agonista ��-adren��rgico). Nas c��lulas musculares lisas, observou-se uma resposta mais acentuada ao agonista ��-adren��rgico, PE, e uma resposta menos significativa ao ATP. O contr��rio foi observado relativamente ��s c��lulas endoteliais. A incuba����o das c��lulas musculares lisas e endoteliais com ATP (300 ��M) causou um aumento dos n��veis de [Ca2+]i. O efeito do ATP (300 ��M) parece envolver a ativa����o de recetores dos subtipos P2X1 e P2X3 sens��veis ao bloqueio com NF023 (3��M) e A317491 (100 nM), respetivamente. J�� o aumento dos n��veis [Ca2+]i produzido pelo ADP (300 ��M) parece envolver a ativa����o de recetores P2Y1, P2Y12 e P2Y13 mediante o antagonismo produzido pelos antagonistas MRS 2179 (0,3��M), AR-C66096 (0,1 ��M) e MRS 2211 (10��M), respetivamente. Os dois tipos celulares expressam imunorreatividade contra recetores A2A, A2B, P2X1, P2X3, P2Y1, P2Y12 e P2Y13.

Influence of Soil Chemistry and Plant Physiology in the Phytoremediation of Cu, Mn, and Zn

Different anthropogenic sources of metals can result from agricultural, industrial, military, mining and urban activities that contribute to environmental pollution. Plants can be grown for phytoremediation to remove or stabilize contaminants in water and soil. Copper (Cu), manganese (Mn) and zinc (Zn) are trace essential metals for plants, although their role in homeostasis in plants must be strictly regulated to avoid toxicity. In this review, we summarize the processes involved in the bioavailability, uptake, transport and storage of Cu, Mn and Zn in plants. The efficiency of phytoremediation depends on several factors including metal bioavailability and plant uptake, translocation and tolerance mechanisms. Soil parameters, such as clay fraction, organic matter content, oxidation state, pH, redox potential, aeration, and the presence of specific organisms, play fundamental roles in the uptake of trace essential metals. Key processes in the metal homeostasis network in plants have been identified. Membrane transporters involved in the acquisition, transport and storage of trace essential metals are reviewed. Recent advances in understanding the biochemical and molecular mechanisms of Cu, Mn and Zn hyperaccumulation are described. The use of plant-bacteria associations, plant-fungi associations and genetic engineering has opened a new range of opportunities to improve the efficiency of phytoremediation. The main directions for future research are proposed from the investigation of published results.

Metal ions modulate the folding and stability of the tumor suppressor protein S100A2

Febs Journal (2009)276:1776-1786