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The aim of this study was to evaluate the participation of nitric oxide (NO) in the hypotensive and vasorelaxation effect induced by PBM using an aluminum gallium arsenide (AlGaAs) diode laser (660 nm). Male Wistar rats were treated with the inhibitor of nitric oxide synthase (L-NAME). A red laser (660 nm; 63 J/cm

Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact of simvastatin administration on brain neurodegenerative processes and cognitive damage in sepsis survivors. Here, we investigated the possible neuroprotective role of simvastatin in neuroinflammation, and neurodegeneration conditions of brain structures related to memory in rats at 10 days after sepsis survival. Male Wistar rats (250–300 g) were submitted to cecal ligation and puncture (CLP, n = 42) or remained as non-manipulated (naive, n = 30). Both groups were treated (before and after the surgery) by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline and observed for 10 days. Simvastatin-treated rats that survived to sepsis showed a reduction in the levels of nitrate, IL1-β, and IL-6 and an increase in Bcl-2 protein expression in the prefrontal cortex and hippocampus, and synaptophysin only in the hippocampus. Immunofluorescence revealed a reduction of glial activation, neurodegeneration, apoptosis, and amyloid aggregates confirmed by quantification of GFAP, Iba-1, phospho Ser396-tau, total tau, cleaved caspase-3, and thioflavin-S in the prefrontal cortex and hippocampus. In addition, treated animals presented better performance in tasks involving habituation memory, discriminative, and aversive memory. These results suggest that statins exert a neuroprotective role by upregulation of the Bcl-2 and gliosis reduction, which may prevent the cognitive deficit observed in sepsis survivor animals.

Objetivo: verificar o conhecimento de enfermeiros-pesquisadores em temas relacionados a boas práticas em pesquisa e editoração científica e comparar os resultados de acordo com o grau de formação. Método: estudo descritivo realizado por inquérito on-line com 197 enfermeiros mestres ou doutores de todas as regiões brasileiras. Para levantar o conhecimento utilizou-se um questionário validado, autoaplicável e anônimo. Sobre o escore dos pesquisadores realizaram-se análises descritivas e inferenciais (Teste de Mann-Whitney). Resultados: Entre as 18 questões específicas, a média de acertos foi de 7,1; sendo de 6,4 para mestres e 7,4 para doutores. Houve diferença estatisticamente significativa na média de acertos entre mestres e doutores (p=0,025), e entre bolsistas e não-bolsistas de produtividade (p=0,021), segundo testes de diferença de médias. As questões sobre práticas editoriais predatórias foram aquelas em que os pesquisadores apresentaram os piores escores. Conclusão: Identificamos baixo conhecimento dos participantes independente do grau de formação (mestrado ou doutorado). A ampliação das estratégias de divulgação e articulação desse conhecimento são necessárias para a produção de conhecimento científico de qualidade na área.

An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280–350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E2 levels in the AVPO at 75 min and 300 min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE2 levels in SI. Intracerebroventricular (icv) administration of 5-HT 30 min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-α, IL-1β, IL-6, and IL-10 and spleen TNF-α and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icv prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway.

Background Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. Considering that during SI these important cardiovascular and inflammatory changes take place, we measured the sensitivity of the cardiovascular reflexes baroreflex, chemoreflex, and Bezold-Jarisch that are key regulators of hemodynamic function. We also evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status. Methods We combined cardiovascular recordings, immunofluorescence, and assays of inflammatory markers in male Wistar rats that receive iv administration of LPS (1.5 or 2.5 mg kg−1) to investigate putative interactions of the neuroinflammation in the NTS and in the anteroventral preoptic region of the hypothalamus (AVPO) with the short-term regulation of blood pressure and heart rate. Results LPS induced hypotension, tachycardia, autonomic disbalance, hypothermia followed by fever, and reduction in spontaneous baroreflex gain. On the other hand, during SI, the bradycardic component of Bezold-Jarisch and chemoreflex activation was increased. These changes were associated with a higher number of activated microglia and interleukin (IL)-1β levels in the NTS. Conclusions The present data are consistent with the notion that during SI and neuroinflammation in the NTS, rats have a reduced baroreflex gain, combined with an enhancement of the bradycardic component of Bezold-Jarisch and chemoreflex despite the important cardiovascular impairments (hypotension and tachycardia). These changes in the cardiac component of Bezold-Jarisch and chemoreflex may be beneficial during SI and indicate that the improvement of theses reflexes responsiveness though specific nerve stimulations may be useful in the management of sepsis.

Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor is a counter-regulatory axis that counteracts detrimental renin-angiotensin system (RAS) effects, especially regarding systemic inflammation, vasopressin (AVP) release, and hypothalamic-pituitary-adrenal (HPA) activation. However, it is not completely understood whether this system may control centrally or systemically the late phase of systemic inflammation. Thus, the aim of this study was to determine whether intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation through the activation of humoral pathways in late phase of endotoxemia. Endotoxemia was induced by systemic injection of lipopolysaccharide (LPS) (1.5 mg/kg, i.v.) in Wistar rats. Ang-(1-7) (0.3 nmol in 2 &micro, L) promoted the release of AVP and attenuated interleukin-6 (IL-6) and nitric oxide (NO) levels but increased interleukin-10 (IL-10) in the serum of the endotoxemic rats. The central administration of Mas receptor antagonist A779 (3 nmol in 2 &micro, L, i.c.v.) abolished these anti-inflammatory effects in endotoxemic rats. Furthermore, Ang-(1-7) applied centrally restored mean arterial blood pressure (MABP) without affecting heart rate (HR) and prevented vascular hyporesponsiveness to norepinephrine (NE) and AVP in animals that received LPS. Together, our results indicate that Ang-(1-7) applied centrally promotes a systemic anti-inflammatory effect through the central Mas receptor and activation of the humoral pathway mediated by AVP.

Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles in health and disease. Sepsis is a life-threatening condition characterized by systemic inflammation (SI) and hemodynamic dysfunction. We hypothesized that baroreceptor denervation worsens lipopolysaccharide (LPS) induced-hemodynamic collapse and SI in conscious rats. We combined: (a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like non-lethal dose (b) analysis of the cardiovascular complexity, (c) evaluation of vascular function in mesenteric resistance vessels, and (d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that baroreceptor afferents are key to alleviate LPS-induced hemodynamic collapse, affecting the autonomic control of cardiovascular function, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse are not dependent of each other given that baroreceptor denervation worsened hypotension and reduced SI.

IntroductionLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID.MethodsWe measured CSF NOx levels in patients with PD with and without LID, and in healthy controls. The levels of CSF NOx levels were measured by ozone-based chemiluminescence.Results67 participants were enrolled. CSF NOx levels were higher in patients with PD with LID than in healthy controls (Kruskal-Wallis statistics = 7.24, p = 0.02). CSF NOx levels did not correlate with other clinical variables.ConclusionWe reported higher levels of nitric oxide in the CSF of patients with PD and LID.Highlights–Nitric oxide has a role on levodopa-induced dyskinesias in Parkinson’s disease–We measured CSF nitrite and nitrate in Parkinson’s disease patients with dyskinesias–CSF nitrite and nitrate were higher in Parkinson’s disease patients with dyskinesias

Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles in health and disease. Sepsis is a life-threatening condition characterized by systemic inflammation (SI) and hemodynamic dysfunction. We hypothesized that baroreceptor denervation worsens lipopolysaccharide (LPS) induced-hemodynamic collapse and SI in conscious rats. We combined: (a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like non-lethal dose (b) analysis of the cardiovascular complexity, (c) evaluation of vascular function in mesenteric resistance vessels, and (d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that baroreceptor afferents are key to alleviate LPS-induced hemodynamic collapse, affecting the autonomic control of cardiovascular function, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse are not dependent of each other given that baroreceptor denervation worsened hypotension and reduced SI.

Enquadramento: A higiene oral é um cuidado essencial na assistência de enfermagem. A sua realização auxilia na prevenção de doenças bucais e sistémicas. Objetivo: Identificar a atuação da equipa de enfermagem na higiene oral em ambiente hospitalar. Metodologia: Estudo exploratório, descritivo, transversal, de abordagem quantitativa realizado com profissionais de enfermagem, que atuam na área hospitalar. Foi aplicado um questionário contendo informações sociodemográficas, do trabalho e da atuação dos participantes na higiene oral. Resultados: Cento e quatorze profissionais de enfermagem participaram do estudo, dentre estes, 75,4% relataram que não realizaram a higiene oral no último turno e 44,7% da equipa sugeriu que o doente o fizesse. A sobrecarga de trabalho e a alta rotatividade de doentes foram citadas como impedimentos para realização deste cuidado. Conclusão: A equipa de enfermagem percebe a higiene oral como um cuidado essencial ao doente, contudo a atuação na prática da higiene oral tem sido negligenciada. Neste contexto, este estudo aponta para a necessidade de fornecer atividades de educação permanente sobre esse cuidado em ambiente hospitalar. Background: Oral hygiene is essential in nursing care. It helps in the prevention of oral and systemic diseases. Objective: To identify the performance of the nursing team in oral hygiene in a hospital environment. Methodology: Exploratory, descriptive, cross-sectional study with a quantitative approach carried out with nursing professionals who work in the hospital environment. A questionnaire was applied to participants about their sociodemographic and professional characteristics and the performance of oral hygiene. Results: A total of 114 nursing professionals participated in this study. Of these, 75.4% of participants reported that they had not performed oral hygiene in the last shift, and 44.7% of the team members suggested that the patient should do so. Work overload and high patient turnover were mentioned as constraints to the performance of oral care. Conclusion: The nursing staff perceives oral hygiene as a part of essential patient care; however, oral hygiene practice has been neglected. This study points to the need to provide continuing education activities on this type of care in the hospital environment. Marco contextual: La higiene oral es un cuidado esencial en la atención de enfermería. Su realización ayuda a la prevención de enfermedades orales y sistémicas. Objetivo: Identificar la actuación del equipo de enfermería en la higiene bucal en un ambiente hospitalario. Metodología: Estudio exploratorio, descriptivo, transversal y de enfoque cuantitativo realizado con profesionales de enfermería que trabajan en el área hospitalaria. Se aplicó un cuestionario que contenía información sociodemográfica sobre el trabajo y la actuación de los participantes en la higiene bucal. Resultados: Ciento catorce profesionales de enfermería participaron en el estudio, de ellos el 75,4% informó de que no realizaron la higiene bucal en el último turno y el 44,7% del equipo sugirió que el paciente lo hiciera. La sobrecarga de trabajo y la alta rotación de pacientes se citaron como impedimentos para realizar esta atención. Conclusión: El equipo de enfermería considera la higiene bucal como un cuidado esencial para el paciente, sin embargo, esta práctica de la higiene bucal se ha descuidado. En este contexto, el presente estudio señala la necesidad de realizar actividades de educación permanente en torno a este tipo de cuidado en un entorno hospitalario.

The central nervous system (CNS) is one of the first physiological systems to be affected in sepsis. During the exacerbated systemic inflammatory response at the early stage of sepsis, circulatory inflammatory mediators are able to reach the CNS leading to neuroinflammation and, consequently, long-term impairment in learning and memory formation is observed. The acute treatment with molecular hydrogen (H2) exerts important antioxidative, antiapoptotic, and anti-inflammatory effects in sepsis, but little is known about the mechanism itself and the efficacy of chronic H2 inhalation in sepsis treatment. Thus, we tested two hypotheses. We first hypothesized that chronic H2 inhalation is also an effective therapy to treat memory impairment induced by sepsis. The second hypothesis is that H2 treatment decreases sepsis-induced neuroinflammation in the hippocampus and prefrontal cortex, important areas related to short and long-term memory processing. Our results indicate that (1) chronic exposure of hydrogen gas is a simple, safe and promising therapeutic strategy to prevent memory loss in patients with sepsis and (2) acute H2 inhalation decreases neuroinflammation in memory-related areas and increases total nuclear factor E2-related factor 2 (Nrf2), a transcription factorthat regulates a vast group of antioxidant and inflammatory agents expression in these areas of septic animals.

Here, we investigated the participation of pro and anti-inflammatory cytokines in the spread of repeated audiogenic seizures from brainstem auditory structures to limbic areas, including the hippocampus. We used Wistar Audiogenic Rats (WARs) and Wistars submitted to the audiogenic kindling protocol with a loud broad-band noise. We measured pro and anti-inflammatory cytokines and nitrate levels in the hippocampus of stimulated animals. Our results show that all WARs developed audiogenic seizures that evolved to limbic seizures whereas seizure-resistant controls did not present any seizures. However, regardless of seizure severity, we did not observe differences in the pro inflammatory cytokines IL-1β, IL-6, TNF-α and IFN-α or in the anti-inflammatory IL-10 in the hippocampi of audiogenic and resistant animals. We also did not find any differences in nitrate content. Our data indicate that the spread of seizures during the audiogenic kindling is not dependent on hippocampal release of cytokines or oxidative stress, but the severity of brainstem seizures will be higher in animals with higher levels of cytokines and the oxidative stress marker, nitrate.

A simulação realística possibilita a reprodução de situações reais para o aprimoramento no processo ensinoaprendizagem. Contudo, seu uso nas ciências básicas, especificamente no ensino da fisiologia humana, ainda é incipiente. O objetivo do presente estudo foi implementar o uso do simulador realístico de alta fidelidade no ensino da fisiologia humana no curso de enfermagem. A simulação teve como tema a regulação da pressão arterial. Foi disponibilizado para os alunos um caso clínico no qual pudessem reconhecer em um simulador realístico de alta fidelidade as variações na pressão arterial a curto e longo prazo e sua aplicabilidade no contexto clínico. Foram utilizadas as funções relacionadas ao sistema cardiovascular disponíveis no simulador. De acordo com a cena/evento implementado no simulador, era esperado que o aluno identificasse o tipo de alteração fisiológica resultante. Na sequência, o tema era discutido com foco na fisiologia inserida no contexto clínico. Identificou-se que o uso do simulador realístico no ensino da fisiologia humana é uma ferramenta útil para o desenvolvimento cognitivo do aluno quanto ao funcionamento do corpo humano, especificamente em relação aos mecanismos de regulação da pressão arterial. Tomando como base a experiência desenvolvida infere-se que o uso do simulador realístico de alta fidelidade possibilita a integração teórico-prática com a aplicação clínica, o que consequentemente aumenta as chances no aprendizado sobre a fisiologia do corpo humano.

This study aimed to determine the amount of plasma nitric oxide in clinically stable dogs at different stages of chronic kidney disease (CKD). Five groups of dogs were studied, aged from 4 to 18, comprising of a control group composed of healthy animals (control n=17), group CKD stage 1 (DRC-1, n=12), group CKD stage 2 (CKD-2, n=10) group, CKD stages 3 (CRD-3, n=13) and Group CKD stage 4 (DRC-4, n=10). Dogs with CKD were clinically stable and received no treatment. Two blood samples were collected at 24 hours intervals (repeated measures) to obtain serum and plasma. The serum creatinine values were used to classify dogs as CG, CKD-1, CKD-2, CKD-3 and CKD-4, and were (1.02±0.02mg/dL), (1.07±0.04mg/dL), (1.81±0.03mg/dL), (3.40±0.15mg/dL) and (6.00±0.20mg/dL) respectively. The determination of nitric oxide (NO) was performed by dosing nitrate/nitrite indirectly, and used for measurement of nitrate according to the NO/ozone chemiluminescence. The data were submitted to ANOVA for nonparametric analysis(Kruskal-Wallis) (P

The purpose of this study was to evaluate the acute effect of photobiomodulation therapy (PBM) on arterial pressure in hypertensive and normotensive rats with application in an abdominal region. Normotensive (2K) and hypertensive (2K-1C) wistar rats were treated with PBM. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after PBM application. The nitric oxide (NO) serum concentration was measured before and after PBM application. Vascular reactivity study was performed in isolated thoracic aortas. Aluminum gallium arsenide (GaAlAs) diode laser was used, at 660nm wavelength and 100mW optical output. The PBM application induced a decrease of SAP in 2K-1C rats. In 2K rats, the PBM application had no effect on SAP, DAP and MAP. Moreover, the magnitude of hypotensive effect was higher in 2K-1C than in 2K rats. The PBM application induced a decrease of HR in 2K-1C and 2K, with higher effect in 2K-1C rats. In 2K-1C, the hypotensive effect induced by PBM was longer than that obtained in 2K rats. PBM application induced an elevation of NO concentration in serum from 2K-1C and 2K rats, with higher effect in 2K-1C. In isolated aortic rings PBM effect is dependent of NO release, and is not dependent of nitric oxide synthase (NOS) activation. Our results indicate that the abdominal acute application of PBM at 660nm is able to induce a long lasting hypotensive effect in hypertensive rats and vasodilation by a NO dependent mechanism.

Angiotensin-(1-7) [Ang-(1-7)] is an angiotensin-derived neuropeptide with potential anti-hypertensive and anti-inflammatory properties. However, a possible action of Ang-(1-7) in neuroimmune interactions to regulate inflammatory response has not been explored. Thus, the aim of this study was to determine whether the intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation via sympathetic efferent circuits. Wistar male rats received systemic administration of lipopolysaccharide (LPS) (1.5 mg/Kg). Ang-(1-7) (0.3 nmol in 2 µL) promoted the release of splenic norepinephrine and attenuated tumor necrosis factor (TNF) and nitric oxide (NO), but increased interleukin-10 (IL-10), levels in the serum, spleen, and liver in endotoxemic rats. Furthermore, 6-hydroxydopamine-induced chemical sympathectomy (100 mg/Kg, intravenous) or i.c.v. administration of Mas receptor antagonist A779 (3 nmol in 2 µL) abolished the anti-inflammatory effects of central Ang-(1-7) injection. Moreover, this treatment did not alter the plasmatic LPS-induced corticosterone and vasopressin. The administration of Ang-(1-7) reverted the low resistance in response to catecholamines of rings of thoracic aorta isolated from endotoxemic rats, treated or not, with this peptide by a mechanism dependent on the regulation of NO released from perivascular adipose tissue. Together, our results indicate that Ang-(1-7) regulates systemic inflammation and vascular hyporesponsiveness in endotoxemia via activation of a central Mas receptors/sympathetic circuits/norepinephrine axis and provide novel mechanistic insights into the anti-inflammatory Ang-(1-7) properties.

Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles. We hypothesized that baroreceptor denervation affects lipopolysaccharide (LPS)-induced systemic inflammation (SI) and hemodynamic collapse in conscious rats, and that these parameters are interconnected. We combine: a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like dose b) analysis of the cardiovascular complexity, c) evaluation of vascular function in mesenteric resistance vessels, and d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that sino-aortic afferents are key to alleviate LPS-induced cardiovascular collapse, affecting the autonomic cardiovascular control, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse seem not to be interconnected.

Physical exercise-induced inflammation may be beneficial when exercise is regular but it may be harmful when exercise is intense and performed by unaccustomed individuals/rats. Molecular hydrogen (H2) has recently emerged as a powerful anti-inflammatory, antioxidant and anti-apoptotic molecule in a number of pathological conditions, but little is known about its putative role under physiological conditions such as physical exercise. Therefore, we tested the hypothesis that H2 decreases intense acute exercise-induced inflammation in the hippocampus, since it is a brain region particularly susceptible to inflammation. Moreover, we also assessed hippocampus oxidative status. Rats ran on a sealed treadmill inhaling either the H2 (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and hippocampal samples were collected immediately or 3 h after exercise. We measured hippocampal levels of cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. Exercise increased TNF-α, IL-6 and IL-10 immediately after the session, whereas no change in IL-1β levels was observed. Conversely, exercise did not cause any change in SOD activity, TBARS and NOx levels. H2 inhibited the exercise-induced surges in TNF-α and IL-6, and potentiated the IL-10 surge, immediately after the exercise. Moreover, no change in IL1-β levels of rats inhaling H2 was observed. Regarding the oxidative stress markers, H2 failed to cause any change in SOD activity, TBARS and NOx levels. No significant change was observed in any of the assessed parameters 3 h after the exercise bout. These data are consistent with the notion that H2 acts as a powerful anti-inflammatory agent not only down-modulating pro-inflammatory cytokines (TNF-α and IL-6) but also upregulating an anti-inflammatory cytokine (IL-10) production without affecting the local oxidative stress status. These data indicate that H2 effectively decreases exercise-induced inflammation in the hippocampus, despite the fact that this region is particularly prone to inflammatory insults.

Objective To investigate the anti-inflammatory property of ghrelin treatment on the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-1) axis in Wistar rats that have undergone endotoxemia. Design In this randomized animal study, lipopolysaccharide (LPS) (5 mg/kg; intraperitoneal) was administered to induce endotoxemia, and ghrelin (15 nmol/kg; endovenous) was injected simultaneously. Blood and liver samples were collected 2 h, 6 h and 12 h after LPS administration for analysis. Measurements Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, beta (IL-1β), and IL-6 from both blood and liver were determined by ELISA assay. Serum nitrate was determined by chemiluminescense. Growth hormone receptor (GHR) and growth hormone secretagogue receptor 1a (GHSR-1a) were determined by western blotting. GHR mRNA and IGF-1 mRNA were determined by RT-PCR. Results LPS administration induced a decrease in IGF-1 and GH serum levels, characterizing GH/IGF-1 axis disruption. Ghrelin treatment attenuated the decrease of serum levels of IGF-1 as well as the increase of TNF-α, IL-1β, IL-6 and nitrate induced by LPS. The increase of induced GHSR-1a protein expression seen in the LPS group after 2 h remained until 6 h after ghrelin treatment. However, attenuation of the circulating IGF-1 decrease by ghrelin treatment was not accompanied by changes in GHR protein expression nor GHR and IGF-1 gene expression. Conclusion Ghrelin was able to attenuate changes in the GH/IGF-1 axis observed during systemic inflammation, which may be due to the modulation of pro-inflammatory mediators release.

Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with hypotension, tachycardia, and multiple organs dysfunctions. SI, a hallmark of sepsis can lead to cardiovascular impair...

Objetivo: investigar a correlacao entre indicadores de aterosclerose e indices de oxido nitrico salivar em pacientes edentulos, usuarios de protese total removivel. Metodo: estudo transversal e correlacional. Alem das variaveis sociodemograficas, avaliou-se: Pressao Arterial (PA), Indice Tornozelo Braquial (ITB), Colesterol Total (CT) e glicemia capilar. Amostras de saliva nao estimulada foram coletadas e os niveis de oxido nitrico dosados pela tecnica de quimioluminescencia. As analises descritivas foram realizadas por meio do pacote estatistico IBM SPSS Statistics versao 25. Resultados: A amostra foi constituida por 38 individuos do sexo feminino e 06 do sexo masculino. 38,7% dos individuos apresentaram pressao arterial alterada, 56,8% tolerância diminuida a glicose, 22,7% niveis elevados de colesterol total e 22,7% Indice Tornozelo Braquial maior que 1,3. A media dos niveis de nitrato salivar foi de 462,2µM/mL. Nao houve correlacao entre esse marcador e as demais variaveis. Conclusao: A populacao estudada apresentou elevado risco cardiovascular e grande variacao nos indices de oxido nitrico salivar, com media elevada desse marcador, o que sugere processo inflamatorio bucal. O oxido nitrico salivar nao se mostrou um bom marcador de alteracoes sistemicas.

Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular hydrogen (H2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H2 gas (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)−1β and IL-6] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. In addition, we evaluated the phosphorylation status of intracellular signaling proteins [glycogen synthase kinase type 3 (GSK3α/β) and the cAMP responsive element binding protein (CREB)] that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H2 blunted exercise-induced plasma inflammatory cytokines (TNF-α and IL-6) surges. Regarding the oxidative stress markers, H2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3α/β phosphorylation was not affected by exercise or H2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H2. These data are consistent with the notion that H2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.

Molecular hydrogen (H2) exerts anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Here we tested the hypothesis that H2 modulates cardiovascular, inflammatory, and thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at different doses (0.1 or 1.5 mg/kg, intravenously, to induce mild or severe SI) in male Wistar rats (250–300 g). LPS or saline was injected immediately before the beginning of 360-minute inhalation of H2 (2% H2, 21% O2, balanced with nitrogen) or room air (21% O2, balanced with nitrogen). Deep body temperature (Tb) was measured by dataloggers pre-implanted in the peritoneal cavity. H2 caused no change in cardiovascular, inflammatory parameters, and Tb of control rats (treated with saline). During mild SI, H2 reduced plasma surges of proinflammatory cytokines (TNF-α and IL-6) while caused an increase in plasma IL-10 (anti-inflammatory cytokine) and prevented fever. During severe SI, H2 potentiated hypothermia, and prevented fever and hypotension, which coincided with reduced plasma nitric oxide (NO) production. Moreover, H2 caused a reduction in surges of proinflammatory cytokines (plasma TNF-α and IL-1β) and prostaglandin E2 [(PGE2), in plasma and hypothalamus], and an increase in plasma IL-10. These data are consistent with the notion that H2 blunts fever in mild SI, and during severe SI potentiates hypothermia, prevents hypotension reducing plasma NO production, and exerts anti-inflammatory effects strong enough to prevent fever by altering febrigenic signaling and ultimately down-modulating hypothalamic PGE2 production.

OBJECTIVE To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p

NEW FINDINGS What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H2 S concentration increases. However, the role of endogenous peripheral H2 S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H2 S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). ABSTRACT In recent years, hydrogen sulfide (H2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H2 S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H2 S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220-270 g) to record body core temperature. These animals received an i.p. injection of a systemic H2 S inhibitor (propargylglycine; 50 or 75 mg kg-1 ), immediately followed by an i.p. injection of LPS (50 or 2500 μg kg-1 ), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg-1 significantly attenuated (P

Made available in DSpace on 2018-11-26T17:56:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Citral is a mixture of the two monoterpenoid isomers (neral and geranial) widely used as a health-promoting food additive safe for human and animal (approved by the US Food and Drug Administration). In vitro studies have reported on the capability of citral to reduce inflammation. Here, we report antipyretic effects of citral in vivo using the most well-accepted model of sickness syndrome, i.e., systemic administration of) to rats. Citral given by gavage caused no change in control euthermic rats (treated with saline) but blunted most of the assessed parameters related to the sickness syndrome [fever (hallmark of infection), plasma cytokines (IL-1 beta, IL-6, and TNF-alpha) release, and prostaglandin E-2 (PGE(2)) synthesis (both peripherally and hypothalamic)]. Moreover, LPS caused a sharp increase in plasma corticosterone levels that was unaltered by citral. These data are consistent with the notion that citral has a corticosterone-independent potent antipyretic effect, acting on the peripheral febrigenic signaling (plasma levels of IL-1 beta, IL-6, TNF-alpha, and PGE(2)), eventually down-modulating hypothalamic PGE(2) production. Univ Sao Paulo, Med Sch Ribeirao Preto, BR-14049900 Sao Paulo, Brazil Univ Estadual Paulista, Biosci Inst, Dept Physiol, Nat Prod Lab, BR-18618970 Sao Paulo, Brazil Univ Sao Paulo, Nursing Sch Ribeiro Preto, BR-14040902 Sao Paulo, Brazil Univ Sao Paulo, Dept Morphol Physiol & Basic Pathol, Dent Sch Ribeirao Preto, BR-14040904 Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Biosci Inst, Dept Physiol, Nat Prod Lab, BR-18618970 Sao Paulo, Brazil FAPESP: 2016/17681-9