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PROGRAMA MULTICÊNTRICO DE PÓS-GRADUAÇÃO EM CIÊNCIAS FISIOLÓGICAS (PMPGCF)

UNIVERSIDADE FEDERAL DA PARAÍBA

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2024
Descripción
  • CECÍLIA BURLE DE AGUIAR
  • Heart Rate Variability Assessment in Post-COVID-19 Patients at a Primary Care Unit in João Pessoa - Paraíba
  • Asesor : CAMILLE DE MOURA BALARINI
  • Fecha: 04-oct-2024
  • Hora: 08:30
  • Mostrar Resumen
  • The study investigated the impacts of SARS-CoV-2 infection on the autonomic cardiovascular regulation of recovered patients, analyzing heart rate variability (HRV) and blood pressure parameters at different stages of recovery. The research was conducted at a Family Health Unit in João Pessoa, Paraíba, including patients who had experienced varying severities of the disease, with follow-up periods of up to 180 days post-infection. The Valsalva maneuver was used to assess autonomic function, comparing the results with a healthy control group. The findings indicated that post-COVID-19 patients showed significant alterations in HRV parameters, such as decreased SDNN and RMSSD, suggesting an autonomic imbalance characterized by sympathetic dominance and reduced parasympathetic tone. The abnormal response to the Valsalva maneuver, with an increase in pNN50 and absence of the expected drop in blood pressure, further supports the presence of prolonged autonomic dysfunction in these individuals. These findings highlight the need for continuous monitoring of post-COVID-19 patients to promptly identify changes in autonomic regulation and prevent future complications. HRV assessment proved to be an effective tool for detecting and tracking dysautonomia in patients after infection, contributing to clinical management and a better understanding of the disease's autonomic sequelae.
  • NOÊMIA NIELLY AMARAL NOGUEIRA
  • EVALUATION OF THE IMMUNOMODULATORY EFFECTS OF BD-8, BD-15, AND DIGOXIN MOLECULES IN MYCOBACTERIUM SMEGMATIS INFECTION MODELS
  • Asesor : SANDRA RODRIGUES MASCARENHAS
  • Fecha: 18-sep-2024
  • Hora: 09:00
  • Mostrar Resumen
  • Cardiotonic steroids are organic compounds that have the property of inhibiting Na⁺/K⁺-ATPase. It has been described in the literature that ouabain and digoxin are endogenous molecules capable of interfering with various aspects of the immune response. Recently, new cardiotonic steroids were synthesized from digoxin: BD-8 (8-benzylidene digoxin) and BD-15 (15-benzylidene digoxin). However, little is known about the effect of these compounds on inflammatory and infectious processes. In this context, the aim of this work is to evaluate the effects of the molecules BD-8, BD-15, and digoxin in Mycobacterium smegmatis infection models using the murine macrophage line RAW 264.7. Initially, in vitro susceptibility assays against Mycobacterium smegmatis were performed. For cell viability studies, the colorimetric MTT method was used with different concentrations (10 μM, 5 μM, 1 μM, 0.1 μM, and 0.01 μM) at 24, 48, and 72 hours. For the evaluation of the therapeutic effect, colony-forming unit (CFU) counting was performed in plate assays, where RAW cells were infected with Mycobacterium smegmatis and treated with the steroids. For cytokine measurement, the enzyme-linked immunosorbent assay (ELISA) method was used. Evaluating the Minimum Inhibitory Concentration (MIC), it was observed that the molecules did not inhibit bacterial growth at concentrations below 200 μg/mL. In the MTT viability results, it was analyzed that BD-8 did not show cytotoxic activity at 24 hours but showed cytotoxicity at 10 μM and 5 μM at 48 hours, and at 10 μM, 5 μM, and 1 μM at 72 hours. BD-15 did not show cytotoxic activity at any concentration or time tested and was the synthetic steroid chosen for the continuation of the experiments. Digoxin did not show cytotoxic activity at 24 hours, but it did show cytotoxicity at 10 μM and 5 μM at 48 hours, and at 10 μM and 1 μM at 72 hours. Regarding CFU counting, BD-15 and digoxin reduced the number of CFUs per well at 10 μM in 24 hours compared to the control. ELISA results showed that IL-6 production increased by 50% with BD-15 treatment and by 19% with digoxin treatment compared to the infected control. IL-1β increased by 13% with BD-15 treatment and by 1% with digoxin treatment compared to the infected control. In TNF-α production, there was an increase of 104% with BD-15 treatment and an increase of 84% with digoxin treatment, all compared to the infected control. Thus, this work contributes to a better understanding of the role of cardiotonic steroids in a mycobacterial infection model.
  • EMMILY FERREIRA DE FARIAS CARDOSO
  • EVALUATION OF VASCULAR FUNCTION IN A MURINE MODEL OF ATHEROSCLEROSIS TREATED WITH LIFEPRO, A NUTRACEUTICAL FORMULATION COMPOSED OF LIMOSILACTOBACILLUS FERMENTUM STRAINS AND POLYPHENOLS
  • Asesor : CAMILLE DE MOURA BALARINI
  • Fecha: 28-ago-2024
  • Hora: 13:30
  • Mostrar Resumen
  • Atherosclerosis is one of the main cardiovascular diseases. Hypercholesterolemia has been the primary atherogenic factor in humans, reinforced by an unregulated diet. Probiotics in association with phenolic compounds have shown efficacy in reducing lipidemia in animals. The Federal University of Paraíba developed a new nutraceutical formulation by combining the probiotic Limosilactobacillus fermentum (strains 139,263,296) with the phenolic compounds quercetin and resveratrol. The present research aimed to investigate the vascular effects of the nutraceutical in apolipoprotein E knockout (apoE-/- ) atherosclerotic mice subjected to an atherogenic diet. Three groups were analyzed: control animals without genetic modification (wild type, WT); apoE-/- animals that received the vehicle, and apoE-/- animals that received the nutraceutical for eight weeks. In the end, the animals were euthanized to evaluate biochemical and inflammatory patterns, lipid deposition, and vascular reactivity in the aorta artery. The administration of the nutraceutical had a hypocholesterolemic effect, reducing cholesterol in treated apoE-/- animals (579±46 mg/dL##*) compared to vehicle apoE-/- animals (978±68 mg/dL), but not in relation to the healthy control group (73±6 mg/dL). There was also a hypoglycemic effect in the treated group (249±16 mg/dL#) compared to the saline apoE-/- group (300±12 mg/dL*). Triglycerides were also reduced in treated animals (211 mg/dL#* vs. apoE-/- saline - 145 mg/dL**). The lipoprotein profile was altered in the vehicle apoE-/- group (HDL - 17±2** vs. WT - 41±2 and LDL - 159±21** vs. WT - 5±0.7); the treatment did not alter HDL and LDL. On the other hand, VLDL was reduced in the treated group (503±62 mg/dL#*) compared to the saline group (779±46 mg/dL**), not differing from healthy animals (29±3 mg/dL). The treatment did not influence food intake and weight. Oxidative stress was higher in the saline apoE-/-group (30±1** vs. WT 13±1) and the LifePro reduced the concentrations (14±2###). Regarding vascular reactivity, the vehicle apoE-/- group showed an increase in vasoconstriction to phenylephrine (Rmax: 88±7**) compared to the healthy control group (Rmax: 70±3) and impaired endothelium-dependent relaxation (apoE-/- vehicle - Rmax: 62±6** and WT-Rmax: 89±5), highlighting endothelial dysfunction in this group. The nutraceutical improved endothelial dysfunction by reducing vasoconstrictor behavior (apoE-/- treated - Rmax: 50±3**##) and increasing relaxation to acetylcholine (apoE-/- treated - Rmax: 107±12##). The treatment restored NO in relaxation and reduced the impact of oxidative stress in an organ bath. Regarding the inflammatory profile, the cytokines TNF (18±1** vs. 7±1) and MCP-1 (145±12** vs. 77±8) were higher in the saline apoE-/- group compared to WT, while IL-6 and IL-10 showed no changes between groups. The treatment did not modify cytokine levels. Lipid deposition in the aortic arch was accentuated in saline apoE-/- (45%±2%**), while treatment (27±2%##) reduced the plaque percentage by 1.2 times. Thus, we suggest that the treatment proved effective in a murine model of atherosclerosis.
  • EMILLE RAULINO DE BARROS
  • Impact of temperature variations on the physiology of the Aedes aegypti mosquito.
  • Asesor : FABIOLA DA CRUZ NUNES
  • Fecha: 28-ago-2024
  • Hora: 09:00
  • Mostrar Resumen
  • The Aedes aegypti mosquito is the main vector of arboviruses such as dengue, chikungunya and zika. It is known that climatic variables interfere in the dynamics of the vector, which can contribute to its population increase, and consequently to the increase in disease transmission. The present study aimed to analyze the influence of temperature on the development time of Aedes aegypti mosquitoes. Eggs of Ae. aegypti strain Lapavet-SD were used, obtained from the colony of the Laboratory of Biotechnology Applied to Parasites and Vectors of CBiotec-UFPB, which is kept in a BOD greenhouse, under controlled temperature conditions of 28 ± 2°C, relative humidity of 75 ± 5% and photoperiod of 12 hours of light and dark. For the tests, 180 eggs were used, which were subdivided into six groups, two of which were subjected to a temperature of 20 ± 2°C, two to a temperature of 28 ± 2°C and the others to 36 ± 2°C. The development time from the egg stage until the death of the last mosquito was determined by means of survival analysis using the Log-rank method (Mantel Cox) and the production of nitric oxide (NO) by hemocytes using the Griess method. The statistical analysis was performed using the GraphPrism 8.0.1 program and P < 0.05 was considered for significant differences. As a result, it was possible to verify a significant difference between the development curves in the survival of Aedes aegypti mosquitoes. At a temperature of 28°C (control group), the average duration of the larval stage was 7 days, while at 20°C it was 11 days and at 36°C, the larval stage lasted 3 days. Furthermore, it was found that the average duration of the pupal stage was 3 days in the control group (28°C), while in the group raised at 20°C it was 7 days and at a temperature of 36°, 11 days. The duration of the adult stage, in mosquitoes exposed to a temperature of 28°C was 27 days. Mosquitoes raised at a temperature of 20°C, lived 152 days, while at a temperature of 36°C they survived 19 days. Furthermore, there was no significant difference in the production of nitric oxide between the control group and the group raised at a temperature of 20°C. However, nitric oxide levels in the test group (36°C) were high. These results contribute to the understanding of the relationship between temperature and the development of the Aedes aegypti mosquito, thus predicting possible changes in its distribution patterns in relation to climate change.
  • JOÃO PAULO CARVALHO DE LIMA
  • STUDY OF THE EFFECTS OF CHALCONES ON THE DEVELOPMENT AND IMMUNE SYSTEM OF MOSQUITOES AEDES AEGYPTI L. (DIPTERA: CULICIDAE)
  • Fecha: 23-ago-2024
  • Hora: 10:00
  • Mostrar Resumen
  • Responsible for transmitting several arboviruses, such as dengue, zika, and chikungunya, the Aedes aegypti mosquito is undergoing a process of population expansion, in part due to the inefficiency of the control methods used. Synthetic compounds were trained by the scientific community due to their wide biological applicability. In this sense, the search for new synthetic molecules with insecticidal activity is of great value. Therefore, the objectives of this study are to evaluate the effect of chalcones (CH) on the development and immune system in Ae. aegypti, its activity in silico, and toxicity in Artemia salina (AS). As a methodology, to evaluate insecticidal activity on Ae. aegypti, concentrations between 2.5 and 1000 ppm were used, and mortality (Mt) was assessed at 24 and 48 hours. Scanning electron microscopy (SEM) was used for morphological analysis of eggs upon exposure to CH. For the immunological analysis of the larvae (L3), nitrite ion (NO2-) concentrations and total hemocyte profile in the hemolymph pool were evaluated. Control groups were exposed to dechlorinated water, Tween® 80, and 20 a (2%). The experiments were performed in triplicate. For statistical analysis, the following were used: ANOVA, Tukey post test, and p<0.05 (GraphPad Prism 8.0). As a result, CH demonstrated conformational stability and lower binding energy (CHN: -126,547 kcal/mol-1) and CHH: -128,536 kcal/mol-1) when compared to co-crystallized ligands. In larvicidal activity, there was greater Mt in the 48h period, shortening the LC50: 10.04 ppm (24h) and 6.84 ppm (48h) for CHH; CHF: 42.01 ppm (24h) and 8.46 ppm (48h); BCH: 195.6 ppm (24h) and 161.8 ppm (48h); and CHN 595.6 ppm (24h) and 553.4 ppm (48h). In the pupicide and adulticide trials, BCH and CHN had higher Mt in 24h, LC50 = 562.1 and 893.7 ppm and Mt with 550 and 1000 ppm, respectively. In the hatchability test, there was a reduction in hatchability by 97.4%. In the SEM analysis, CHH and CHF caused visible damage to the egg exochorium. In toxicity tests, there was a lower Mt compared to BCH: 4.9±0.6% and CHN: 4.0±0.6% (24h). The immunological activity mediated by CH demonstrated a quantitative increase in hemocytes, CHH: 9.6±1.3% (24h) and 10.7±8.8% (48h); ICC: 10.91±1.3% (24h) and 13.7±7.8% (48h); CHN: 10.7±1.5% (24h) and 11.1±7.8% (48h); an increase by BCH: 22.3±1.3% (24h) and 16.4±1.8 % (48h), and an increase in NO2- in all CH (24h: 18.9±0.6% and 48h: 20.9±0.6%). The results highlight CH as molecules with significant insecticidal and immunomodulatory activity, combined with low toxicity and proven efficacy in in silico studies. These properties show promise for the development of new insecticidal agents with potential impacts on public health.
  • LAYANE DA SILVA LIMA
  • VASORELAXANT EFFECT AND MECHANISM OF ACTION OF 4-NITROOXYBUTYL 4-METHYLBENZOATE ON THE VASCULAR FUNCTION OF NORMOTENSIVE RATS
  • Fecha: 11-jun-2024
  • Hora: 14:00
  • Mostrar Resumen
  • Organic nitrates are used in the treatment of cardiovascular diseases as they are donors of nitric oxide. Therefore, this work aimed to investigate the mechanism of action of a new organic nitrate, 4-methylbenzoate 4-nitrooxybutyl (NIB7) on the vascular function of the superior mesenteric artery of rats. The protocol was the ex vivo approach, where the mesenteric artery rings were isolated in an aerated Tyrode nutrient solution with a carbogenic mixture, using compact organ bath equipment. After stabilization for one hour, the viability of the rings was checked and the endothelium test was performed. When the rings were subjected to contraction with phenylephrine (FEN), NIB7 showed vasorelaxant activity independent of functional endothelium (pD2= 6,328 ± 0,11 n=10; Emáx= 107,6 ± 3,07 n=10). Relaxation was attenuated when another contracture agent, 60 mM KCl, was used (pD2 = 5,0 ± 0,09 n=7, *p< 0,05). In the presence of L-NAME, a non-selective NOS inhibitor, there was no difference in the vasorelaxant effect. When incubating the rings with a NO scavenger (HDX), vasorelaxation was attenuated (pD2 = 5.11 ± 0.08 n=7, *p < 0.05). When inhibiting soluble guanylyl cyclase (GCs) with ODQ, the effect was also attenuated (pD2= 3.819 ± 0.10 n=7; Emax= 75.83 ± 7.50 n=7, *p< 0.05). When using 20mM KCl, a potassium efflux modulator, and 3mM TEA, a nonspecific potassium channel blocker, potency was attenuated (pD2 = 5.525 ± 0.05 n=7 and 5.320 ± 0.05 n=7, respectively, * p<0.05). When investigating potassium-specific channels, using 1 mM 4-AP (for voltage-operated channels), 1 mM TEA (calcium-sensitive channels), BaCl2 (input rectifying channels), GLIB (ATP-dependent channel), it was seen that no subtype demonstrated a significant influence on the relaxation induced by the compound when evaluated in isolation. When the rings were pre- exposed to a high concentration of NIB7 (100μM) to assess the development of vascular tolerance, attenuation of potency was observed (pD2= 5.095 ± 0.10 n=6, *p< 0.05). With this, it was seen that NIB7 is an NO donor, whose effect is independent of the endothelium. It suggests the involvement of the NO-GCs-PKG pathway, with the participation of potassium channels, despite not having a specific channel. Finally, the compound appears to induce tolerance to vasorelaxation in the ex vivo experimental approach. However, more studies are needed to better clarify this effect.
  • CLARA RITTMEYER RUIZ
  • Effects of the new organic nitrate 4-nitrooxybutyl 4-chlorobenzoate on the vascular function of the cranial mesenteric artery of normotensive rats.
  • Fecha: 26-abr-2024
  • Hora: 14:00
  • Mostrar Resumen
  • Cardiovascular diseases (CVDs) are prevalent and lead the causes of death in the world population. The pathogenesis of CVDs is related to functional and morphological changes in the heart and/or blood vessels. Endothelial dysfunction causes increased con- tractility and vascular resistance, observed in diseases such as atherosclerosis and arteri- al hypertension. Organic nitrates are nitric oxide (NO) donors and potent vasodilators. Thus, the research aims to investigate the mechanism of action of a new organic nitrate, 4-nitrooxybutyl 4-chlorobenzoate (NHJB2), on the vascular function of the cranial mes- enteric artery of normotensive Wistar rats (Rattus norvegicus). The ex vivo experi- mental protocols were carried out using the compact organ bath equipment (76-00xx series, Panlab, S.L. Havard Apparatus Spain). Cranial mesenteric artery rings were iso- lated using aerated Tyrode nutrient solution with a carbogen mixture at a temperature of 37°C. After stabilization for one hour, the viability of the rings was checked and the endothelium test was performed. Next, pre-contraction was performed with phe- nylephrine (FEN) and a concentration-response curve was performed using NHJB2 to evaluate the vasorelaxant effect. NHJB2 was able to evoke a vasorelaxant response in the absence of endothelium (E-) in rings pre-contracted with FEN (Emax=114.7±4.2; pD2=6.64 ±0.08). When incubating positive endothelium rings (E+) with L-NAME (100 μM) the potency (pD2) was attenuated (5.52 ± 0.02), and the Emax (109.0 ± 0.95) remained the same. Vasorelaxation was attenuated in rings pre-contracted with 60 mM KCl (pD2=5.18±0.03). In the presence of a NO scavenger - HDX (100 μM) vasorelaxation was attenuated (Emax=74.05±6.22 and pD2=4.08±0.06). When blocking soluble guanylyl cyclase (GCs) with ODQ (10 μM), vasorelaxation was also attenuated (Emax=96.84±10.86 and pD2=3.69±0.06). When incubating the rings with 20 mM KCl and 3 mM TEA the potency was attenuated (5.35±0.05 and 5,03±0,04, respectively). Thus, we suggest that the vasorelaxant response induced by NHJB2 does not depend on the presence of the endothelium, it is effected by the mechanism of NO donation and activation of the NO/GCs pathway and participation of potassium (K+) channels. The next steps involve investigating K+ channel subtypes and evaluating acute desensitiza- tion to NHJB2.
  • JULIANA TELES DE ANDRADE
  • EFFECTS OF KONJAC GLUCOMANNAN (KONJAC MASSA MF®) CONSUMPTION ON THE GLYCEMIC AND LIPID PROFILE OF TYPE 1 DIABETIC MICE
  • Asesor : JOSIANE DE CAMPOS CRUZ
  • Fecha: 29-feb-2024
  • Hora: 14:00
  • Mostrar Resumen
  • Type 1 diabetes mellitus (T1DM) is a metabolic condition characterized by immune activation against pancreatic beta cells. Therapies that enhance insulin levels and sensitivity are vital for individuals with T1DM. Diet, including dietary fibers, emerges as a promising non-pharmacological intervention for glycemic control. Konjac glucomannan (KGM) stands out for its hypoglycemic properties in T1DM animal models. Thus, this study aimed to assess the effects of KGM, in the form of the commercial product Konjac Massa MF®, on the glycemic and lipid profile of mice with STZ-induced T1DM. Male C57BL/6J mice, induced to T1DM with STZ, were treated for four weeks with Konjac Massa MF® (120 mg/kg/day ig). We monitored glycemia, weight gain, and water and feed consumption during treatment. We also conducted glucose (IPGTT) and insulin (IPITT) tolerance tests, followed by plasma collection for biochemical analyses and tissue preservation in 10% formalin for histological analyses. Results showed a significant reduction in fasting glycemia in diabetic mice treated from the third week compared to untreated diabetics (245.20 ± 26.91 vs 412.10 ± 25.18mg/dL). However, there was no significant difference in glucose tolerance between treated and untreated diabetic groups. The treated group exhibited improved insulin sensitivity (209.90 ± 57.20 vs 378.50 ± 61.97 mg/dL; 60 min: 213.70 ± 48.49 vs 361.00 ± 61.34 mg/dL; 90 min: 197.90 ± 51.85 vs 316.30 ± 60.74 mg/dL; 120 min: 234.50 ± 59.23 vs 318.30 ± 54.78 mg/dL). Treatment also reduced serum alanine aminotransferase (ALT) levels (39.39 ± 6.89 vs 82.83 ± 25.19 nmol/dL), suggesting a potential hepatoprotective effect of KGM. We conclude that Konjac Massa MF® is a promising therapeutic agent for improving insulin sensitivity and hepatic function in T1DM models, with no adverse side effects. Further research is crucial to unravel the protective mechanisms of KGM and determine its clinical applicability in the management of T1DM and its associated complications.
  • JULIANA TELES DE ANDRADE
  • EFFECTS OF KONJAC GLUCOMANNAN (KONJAC MASSA MF®) CONSUMPTION ON THE GLYCEMIC AND LIPID PROFILE OF TYPE 1 DIABETIC MICE
  • Asesor : JOSIANE DE CAMPOS CRUZ
  • Fecha: 29-feb-2024
  • Hora: 14:00
  • Mostrar Resumen
  • Type 1 diabetes mellitus (T1DM) is a metabolic condition characterized by immune activation against pancreatic beta cells. Therapies that enhance insulin levels and sensitivity are vital for individuals with T1DM. Diet, including dietary fibers, emerges as a promising non-pharmacological intervention for glycemic control. Konjac glucomannan (KGM) stands out for its hypoglycemic properties in T1DM animal models. Thus, this study aimed to assess the effects of KGM, in the form of the commercial product Konjac Massa MF®, on the glycemic and lipid profile of mice with STZ-induced T1DM. Male C57BL/6J mice, induced to T1DM with STZ, were treated for four weeks with Konjac Massa MF® (120 mg/kg/day ig). We monitored glycemia, weight gain, and water and feed consumption during treatment. We also conducted glucose (IPGTT) and insulin (IPITT) tolerance tests, followed by plasma collection for biochemical analyses and tissue preservation in 10% formalin for histological analyses. Results showed a significant reduction in fasting glycemia in diabetic mice treated from the third week compared to untreated diabetics (245.20 ± 26.91 vs 412.10 ± 25.18mg/dL). However, there was no significant difference in glucose tolerance between treated and untreated diabetic groups. The treated group exhibited improved insulin sensitivity (209.90 ± 57.20 vs 378.50 ± 61.97 mg/dL; 60 min: 213.70 ± 48.49 vs 361.00 ± 61.34 mg/dL; 90 min: 197.90 ± 51.85 vs 316.30 ± 60.74 mg/dL; 120 min: 234.50 ± 59.23 vs 318.30 ± 54.78 mg/dL). Treatment also reduced serum alanine aminotransferase (ALT) levels (39.39 ± 6.89 vs 82.83 ± 25.19 nmol/dL), suggesting a potential hepatoprotective effect of KGM. We conclude that Konjac Massa MF® is a promising therapeutic agent for improving insulin sensitivity and hepatic function in T1DM models, with no adverse side effects. Further research is crucial to unravel the protective mechanisms of KGM and determine its clinical applicability in the management of T1DM and its associated complications.
  • DEYSE CRISTINA MADRUGA CARVALHO
  • AVALIAÇÃO DA ATIVIDADE ANTIVIRAL DA OUABAÍNA CONTRA O ZIKA VÍRUS EM MODELOS IN VITRO, IN VIVO E IN SILICO
  • Fecha: 29-feb-2024
  • Hora: 13:30
  • Mostrar Resumen
  • Ouabain, a cardiotonic steroid known as Na+ /K+ -ATPase inhibitor, has been described as an immunomodulatory substance by our group. In addition, the antiviral activity of ouabain has been reported in several studies. Zika virus (ZIKV) is an emerging arbovirus associated with neurological disorders. Currently, there are no vaccines or antivirals available to treat the disease caused by ZIKV. Then, this work aimed to evaluate the anti-ZIKV activity of ouabain in vitro, in silico and in vivo. Initially, Vero cells were used to determine the non-toxic concentrations of ouabain and then, the antiviral activity was evaluated in this cell type. Ouabain presented a dose-dependent inhibitory effect against ZIKV, mainly when added post infection. The reduction of infectious virus was accompanied by a decrease in ZIKV RNA levels, suggesting that the mechanism of ZIKV inhibition by ouabain occurred at the replication step. To evaluate the activity of ouabain in a more clinical approach in relation to ZIKV infection, an in vitro model of human neural progenitor stem cells (NS/PCs) and an animal model of Congenital Zika Virus Syndrome (SCZ) were performed. In NS/PCs, ouabain reduced ZIKV infection in this cell type and blocked the impairment of neurogenesis triggered by the virus. Additionally, in an animal model of SCZ, ouabain protected the fetus from microcephaly triggered by the infection. This is might related to the ability of ouabain to inhibit the virus in yolk sac microglial progenitors. In addition to antiviral activity, ouabain was able to reduce the pro-inflammatory cytokine IL-1β in the placenta, demonstrating its anti-inflammatory potential in this model. Finally, we performed a molecular docking procedure followed by molecular dynamics simulations to predict the interaction between ouabain and the main drug targets in ZIKV proteome (NS3 Helicase, NS5 Mtase and NS5 RdRp). Our in silico data demonstrated a conformational stability and favorable binding free energy of ouabain in the biding sites of the NS5-RdRp and NS3-helicase proteins, suggesting inhibition of these viral proteins by this steroid.Together, these data demonstrate the antiviral action of ouabain in ZIKV infection, revealing this substance as a potential compound for the treatment of infection caused by this virus. In this way, this study contributes to highlighting the effectiveness of cardiotonic steroids as promising antiviral agents, in addition to generating more understanding about the biological functions of ouabain.
  • CLENIA DE OLIVEIRA CAVALCANTI
  • EVALUATION OF THE ANTI-INFLAMMATORY ACTIVITY OF SODIUM NITRITE AND 2-NITRATE-1,3-DIBUTOXYPROPANE (NDBP) IN EXPERIMENTAL ATHEROSCLEROSIS.
  • Fecha: 26-ene-2024
  • Hora: 08:30
  • Mostrar Resumen
  • Ischemic heart disease and stroke are among the leading causes of death in the world and maintains a close relationship with atherosclerosis, a chronic inflammatory disease of the vascular system characterized by intense activity innate and adaptive immunology. In the atherogenic process, a reduction in bioavailability of nitric oxide (NO) and increase in reactive oxygen species (ROS). In this sense, an improved understanding of new therapeutic alternatives to improve the bioavailability of NO are necessary, which includes studies on new classes of NO-donating drugs and the nitrate-nitrite-NO pathway. The objective of study was to evaluate the anti-inflammatory activity of sodium nitrite (NaNO2) and 2-nitrate- 1,3-dibutoxypropane (NDBP) in a model of acute inflammation and atherosclerosis experimental. Acute inflammation: C57BL/6 (controls) and ApoE-/- mice were treated with NaNO2 (dose 0.1mmoL/kg) or NDBP (dose 40mg/kg) for three days. One hour after the last day of treatment, the animals were stimulated with zymosan (2mg/mL) in order to induce inflammation in the peritoneum. After 4 hours, peritoneal fluid was collected and used to count total and differential cells by microscopy optics and for quantification of cytokines (IL-6, IL-10, TNF-α and MCP-1) by Elisa. Chronic inflammation: ApoE-/- mice, upon reaching 8 weeks of age, received Western atherogenic diet for 12 weeks and their controls received a standard diet to rodents. During the last 3 weeks they received NaNO2 by gavage (0.1mmoL/kg/day), NDBP (40mg/kg) or saline. At the end of the treatment, the blood collection for analysis of lipid profile, lipid peroxidation, plasma nitrite and cytokines (IL-6, IL-10, TNF-α and MCP-1) and aortas were removed and processed for histological evaluation of atherosclerotic plaque deposition (oil red staining), production of ROS (labeling with dihydroethide - DHE) and NO (labeling with diaminofluorescein - DAF). Data were expressed as mean ± standard error of mean and statistical comparisons were made by ANOVA, followed by post hoc Tuckey, considering p<0.05. In the peritonitis model, zymosan, as expected, induced an increase in cell migration and levels of pro-inflammatory cytokines in the peritoneum.NaNO2 treatment was able to reduce the total number of cells to peritoneal cavity, by reducing polymorphonuclear migration in mice C57BL/6 and Apoe-/- mice reduced plasma levels of the cytokines IL-10, TNF-α and MCP-1. NDBP increased cell migration in both lineages. At the experimental atherosclerosis model, treatment with NaNO2 reduced the deposition of atherosclerotic plaque, plasma MCP-1 levels, systemic and intracellular oxidative stress situ in the aorta, independent of changes in NO levels, plasma nitrite and profile lipid. NDBP differed from NaNO2 only in MCP-1 levels, increasing this cytokine in plasma. These results suggest that NaNO2 has an anti-inflammatory effect in a model of acute and chronic inflammation, being able to reduce plaque deposition atherosclerosis by mechanisms involving the reduction of oxidative stress and MCP-1. AND that NDBP has a dual effect, with pro-inflammatory action in a model of peritonitis and antiatherogenic action.
2023
Descripción
  • GEOVANE FERNANDES MUNIZ
  • Immunophysiology in the dynamics of vector control: Investigation of the effects of kójic acid (5-Hydroxy-2-hydroxymethyl-4H-4-pyranone) on the development of Aedes aegypti L. (Diptera: Culicidae).
  • Asesor : FABIOLA DA CRUZ NUNES
  • Fecha: 01-dic-2023
  • Hora: 10:00
  • Mostrar Resumen
  • Control of Ae. aegypti is associated with a shocking reduction in damage involving arboviruses of great clinical and epidemiological relevance. Control methods can act at any stage of the vector's life, from embryonic development to its winged form. In the oviposition process, eggs in the first stage of embryogenesis are of light color and allow free passage of water through the egg shell. During this stage, the process of melanization occurs, which gives the embryo resistance to desiccation and, consequently, a greater viability of the ejaculation of the eggs after long periods in dry environments. Also, NO (Nitric oxide) is presented as a potential mechanism involved in physiological functions such as the signaling of epithelial cells and the induction of the innate immunity of Ae. aegypti. Attached to this panorama, it is interesting to highlight the role of tyrosinase that participates in the formation of melanine as a catalyst, and that is evident as a potential target in the control of Ae. aegypti. It is then that KA (kojic acid), a chemical commonly used for skin whitening, comes into play, as it has inhibitory properties in the synthesis of tyrosinase, corroborating the justification of a potential method of control of Ae. aegypti. The results showed that the production of NO in larvae (L4) exposed to KA for 24h, had a higher index in the control group (concentration of 65.76 ± 6.65 microMolar/mL) compared to the test groups (exposed to 100, 500 e 1000 ppm). The concentration of NO in the control group was 65.76 + 6.65 μM/mL, significantly higher compared to the LOSC (Larvas de ovos sem cutícula or Larvae of eggs without cuticles) test group, whose concentration was 4.46 + 5.40 μM /mL. There was no lethality of the compound for the different life stages of Ae. aegypti; experiments were conducted with KA exposure at 1000 ppm for 24 hours. There was no significant difference in the range of eclodability, nor was there any difference in egg size in the different groups analysed. The clarification corroborated the coloring results of the eggs, showing that those with the formed serous cutile had darker pigmentation, suggesting a higher presence of melanine. The analysis of the cell profile of the hemolinfa of larvae of Ae. aegypti exposed to KA allowed to identify the predominance of hemocyte types, pro-hemocyte, plasmocyte and granulocyte in approximately 20% for the three most obvious cell types. When analyzing the larvae size (L4), the difference in size equivalent to about 1.5 mm was observed between larvaes in the control group with an average of 6.5 mm and the LOSC group with a average of 8 mm. And finally, the results allowed to observe an increase between 30 and 50% of the amount of larvae that metamorphosis to the pupa phase around the 10th and 12th day of the life cycle. Our studies suggest that KA can influence the development and possible changes in the immune response of Ae. aegypti through physiological mechanisms that justify the continuation of promising studies with the arthropod.
  • GEOVANE FERNANDES MUNIZ
  • Immunophysiology in the dynamics of vector control: Investigation of the effects of kójic acid (5-Hydroxy-2-hydroxymethyl-4H-4-pyranone) on the development of Aedes aegypti L. (Diptera: Culicidae).
  • Asesor : FABIOLA DA CRUZ NUNES
  • Fecha: 01-dic-2023
  • Hora: 10:00
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  • Control of Ae. aegypti is associated with a shocking reduction in damage involving arboviruses of great clinical and epidemiological relevance. Control methods can act at any stage of the vector's life, from embryonic development to its winged form. In the oviposition process, eggs in the first stage of embryogenesis are of light color and allow free passage of water through the egg shell. During this stage, the process of melanization occurs, which gives the embryo resistance to desiccation and, consequently, a greater viability of the ejaculation of the eggs after long periods in dry environments. Also, NO (Nitric oxide) is presented as a potential mechanism involved in physiological functions such as the signaling of epithelial cells and the induction of the innate immunity of Ae. aegypti. Attached to this panorama, it is interesting to highlight the role of tyrosinase that participates in the formation of melanine as a catalyst, and that is evident as a potential target in the control of Ae. aegypti. It is then that KA (kojic acid), a chemical commonly used for skin whitening, comes into play, as it has inhibitory properties in the synthesis of tyrosinase, corroborating the justification of a potential method of control of Ae. aegypti. The results showed that the production of NO in larvae (L4) exposed to KA for 24h, had a higher index in the control group (concentration of 65.76 ± 6.65 microMolar/mL) compared to the test groups (exposed to 100, 500 e 1000 ppm). The concentration of NO in the control group was 65.76 + 6.65 μM/mL, significantly higher compared to the LOSC (Larvas de ovos sem cutícula or Larvae of eggs without cuticles) test group, whose concentration was 4.46 + 5.40 μM / mL. There was no lethality of the compound for the different life stages of Ae. aegypti; experiments were conducted with KA exposure at 1000 ppm for 24 hours. There was no significant difference in the range of eclodability, nor was there any difference in egg size in the different groups analysed. The clarification corroborated the coloring results of the eggs, showing that those with the formed serous cutile had darker pigmentation, suggesting a higher presence of melanine. The analysis of the cell profile of the hemolinfa of larvae of Ae. aegypti exposed to KA allowed to identify the predominance of hemocyte types, pro-hemocyte, plasmocyte and granulocyte in approximately 20% for the three most obvious cell types. When analyzing the larvae size (L4), the difference in size equivalent to about 1.5 mm was observed between larvaes in the control group with an average of 6.5 mm and the LOSC group with a average of 8 mm. And finally, the results allowed to observe an increase between 30 and 50% of the amount of larvae that metamorphosis to the pupa phase around the 10th and 12th day of the life cycle. Our studies suggest that KA can influence the development and possible changes in the immune response of Ae. aegypti through physiological mechanisms that justify the continuation of promising studies with the arthropod.
  • ÉSSIA DE ALMEIDA LIMA
  • Evaluation of the mechanisms of action involved in the anti-inflammatory LQB 118 effect
  • Fecha: 30-ago-2023
  • Hora: 08:00
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  • LQB 118 is a synthetic hybrid molecule belonging to the group of pterocarpanquinones, with its structure based on two groups of natural bioactive molecules, naphthoquinones and pterocarpans. The immunomodulatory role of LQB 118 has been demonstrated by our research group, however, the mechanisms of action involved are not yet fully elucidated. Therefore, the aim of this work was to evaluate the mechanisms involved in the anti-inflammatory activity of LQB 118 in vitro and in vivo. Initially, for in vitro experiments, Swiss mice received an intraperitoneal injection of thioglycolate (4%). After four days, peritoneal macrophageswere cultured at concentrations of 2x105 , 5x105 or 1,5x106 cells/well. The cells were treated with LQB 118 (0.1 μM, 0.5 μM, 1 μM or 5 μM) in the presence or absence of the inflammatory stimulus, zymosan (0.2 mg/mL), for 40 min or 24 h. Then, supernatants were collected for the quantification of cytokines IL-10 and IL-12 via ELISA and nitric oxide through the Griess reagent. Additionally, phagocytic activity was assessed towards zymosan particles. Finally, in order to examine the mechanism of action of the molecule, cells were incubated with anti-iNOS, anti- NFkB, and anti-p-NFkB antibodies along with fluorescent zymosan particles and analyzed through flow cytometry. Zimosan induced an increase in cytokines and nitric oxide, and treatment with LQB 118 was able to reduce the levels of IL-12 (0.1 μM by 28.7%; 0.5 μM by 31%; 1 μM by 36.8%; and 5 μM by 57.6%) and NO (5 μM by 60.2%) without interfering with IL-10 levels. In addition, LQB 118 negatively modulated the expression of total NFkB (21.7%) and phosphorylated NFkB (59.4%), decreased the phagocytic capacity of peritoneal macrophages (24.1% and 64.4%), ROS production (23.5%), and reduced levels of phosphorylated mTOR (20.2%). Moreover, the effect of LQB 118 was evaluated in vivo, in a zymosan-induced peritonitis model. For this, Swiss mice were treated via i.p. with LQB 118 at doses of 10 or 20 mg/kg. 1 h after treatment, they were stimulated with zymosan (2 mg/mL) to induce peritoneal inflammation. After 4 h, peritoneal lavage was collected and used for total and differential cell counting by light microscopy, for quantification of cytokines TNF- α, IL-1β, IL-6, and IL-10 by ELISA, and for analysis of MAP kinase p38 expression by flow cytometry. Zymosan, as expected, induced an increase in cell migration, cytokine levels, and p38 phosphorylation. Treatment with LQB 118, on the other hand, reduced the total number of cells in the peritoneal cavity, by decreasing the migration of polymorphonuclear cells. Furthermore, this molecule was able to reduce the levels of cytokines IL-1β, TNF-α, and IL-10 and negatively modulate zymosan-induced p38 phosphorylation. Treatment with LQB 118, on the other hand, was able to reduce the total number of cells in the peritoneal cavity (32.6% at a dose of 10 mg/kg or 51.1% at a dose of 20 mg/kg), by decreasing the migration of polymorphonuclear cells (56.7% for 10 mg/kg or 80.4% for 20 mg/kg). Furthermore, this molecule was capable of reducing the levels of the cytokines IL-1β (81.1% or 78.3% for doses of 10 mg/kg or 20 mg/kg, respectively), TNF-α (56.2% at a dose of 20 mg/kg), and IL-10 (71.6% at a dose of 20 mg/kg), and negatively modulating the phosphorylation of p38 induced by zimosan (51.6%).Thus, these data demonstrate the mechanisms involved in the anti-inflammatory activity of LQB 118 and contribute to the understanding of the potentialities of this substance to act in physiological processes.
  • REPHANY FONSECA PEIXOTO
  • Study of the immunological profile of T cell subpopulations naive and memory in convalescent patients from COVID-19
  • Fecha: 04-abr-2023
  • Hora: 08:00
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  • COVID-19 is a severe acute respiratory infection caused by the SARS-CoV-2 virus capable of suffering from different clinical conditions ranging from asymptomatic to severe, in which the host's immune response is crucial for its establishment. Long-lived SARS-CoV-2- specific CD4+ and CD8+ memory T cells are essential for long-term immune protection against COVID-19 as they have an increased ability to restrict viral replication in a secondary infection. Thus, the present study aims to investigate immunomodulatory mechanisms mediated by CD4+ and CD8+ T lymphocyte subtypes in patients who recovered from mild and severe forms of COVID-19 before vaccination by flow cytometry. Thus, peripheral blood samples were obtained from recruited volunteers and distributed into control (CTL - n = 9), mild (n =9), and severe (n = 6) groups. Samples of PBMCs were obtained and incubated under 3 different conditions: unstimulated (medium), and stimulated with SARS- CoV-2 peptides (Pool Spike CoV-2 and Pool CoV-2. CD4+ and CD8+ T cells were analyzed and classified for CCR7+ and CD45RA+ expression in naive CD4+/CD8+ T cells (TN), CD4+/CD8+ central memory T cells (TMC), CD4+/CD8+ effector memory T cells (TME), and CD4+/CD8+ effector memory T cells that reexpress CD45RA (TMERA). Thus, in the different subpopulations mentioned above, cytokines (IL-10, IFN-y, TNF-α, and IL-17) and activation markers (CD69, CD137, and Ki67) were expressed analyzed by flow cytometry. Pool Spthe ike CoV-2 and Pool CoV-2 stimulus elicited a higher frequency of CD8+ TCM cells and CD4+ TEMRA cells in recovered mild group. CD4+ and CD8+ TCM and TEM cells showed heterogeneity in CD137 and CD69 activation marker expressions between mild and severe recovered groups. Also, we observed a predominance in CD137 expression by naive CD4+ and CD8+ cells, TCM, and TEM from the mild recovered group when stimulated with antigenic pools. Additionality, a higher CD69 expression from the severe recovered group by CD4+ and CD8+ TEMRA cells was observed under SARS-CoV-2 Epitope Pools. CD4+ and CD8+ naïve, TCM and TEM cells subsets from recovered mild volunteers had higher expression of TNF-α while the expression partner of IFN-γ, IL-10, and IL-17 point to an antiviral signature by TEMRA CD8+ cells. Our findings contribute to the elucidation of the functional capabilities of each subpopulation of memory T cells during SARS CoV-2 antigenic reexposure, as well as their role in disease outcome in individuals recovered from COVID-19.
  • REPHANY FONSECA PEIXOTO
  • Study of immunological profile of memory T cell subpopulations in COVID-19 convalescent patients
  • Fecha: 04-abr-2023
  • Hora: 08:00
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  • COVID-19 is a severe acute respiratory infection caused by the SARS-CoV-2 virus. The rapid viral spread and social impact of the disease challenged health authorities to seek therapeutic and preventive solutions for the disease, as well as to understand its effects on the human body from an immunological and clinical point of view. Long-lived SARS-CoV-2-specific CD4+ and CD8+ memory T cells are essential for long-term immune protection against COVID-19 as they have an increased ability to restrict viral replication in a secondary infection. Thus, the present study aims to investigate immunomodulatory mechanisms mediated by CD4+ and CD8+ T lymphocyte subtypes in patients who recovered from mild and severe forms of COVID-19 before vaccination by flow cytometry. Thus, peripheral blood samples were obtained from recruited volunteers and distributed into control (CTL - n = 9), mild (n =9) and severe (n = 6) groups. Samples of PBMCs were obtained and incubated under 4 different conditions: unstimulated (medium), stimulated with SARS-CoV-2 peptides (Pool Spike CoV-2 and Pool CoV-2), and stimulated with Staphylococcal enterotoxin B (SEB). CD4+ and CD8+ T cells were analyzed and classified for CCR7+ and CD45RA+ expression in naive CD4+/CD8+ T cells (TN), CD4+/CD8+ central memory T cells (TMC), CD4+/CD8+ effector memory T cells (TME), and CD4+/CD8+ effector memory T cells that reexpress CD45RA (TMERA). Thus, in the different subpopulations mentioned above, the expression of cytokines (IL-10, IFN-y, TNF-α, and IL-17) and activation markers (CD69, CD137, and Ki67) was analyzed by flow cytometry. Our data demonstrate that CD8+ T cells of central memory (TCM) and effector memory that reexpress CD45RA (TEMRA) present a lower frequency than T cells of Effector Memory (EMT) Naive T cells (TN) in the different groups evaluated. Similar results are observed in memory CD4+ T cell subtypes, however naive CD4+ T cells showed a reduced frequency in the recovered mild group. Furthermore, the stimulation by Pool Spike CoV-2 and Pool CoV-2 in TN CD8+ and CD4+ cells, induced an increase in the frequency of IFN-γ, IL-10, and IL-17 in recovered mild and severe groups, respectively. In TEMRA CD8+ and CD4+ cells, in turn, the peptide stimuli induced elevated expression of CD69 in recovered severe group and IFN-γ reduction, especially in the recovered mild group. CD4+ TEM showed an elevated expression of TNF-α in stimulation absence in patients recovered from mild cases of COVID-19. In relation to activation by CD137, Pool CoV-2 was responsible for your expression reduction in the recovered mild and severe group by CD4+ T cells of effector memory. However, Pool Spike CoV-2 and Pool CoV-2 induced an increase in the expression of this marker by TEM CD8+. In addition, Pool Spike CoV-2 also induced an increase of the IL-17 expression in the recovered severe group. TCM CD4+ cells significantly express CD137, IL-10, and TNF-α in Pool Spike CoV-2 presence by the recovered mild group. A high expression of IL-17 is observed in this cell subtype in the severe group with Pool CoV-2 stimulation. The same stimulus promotes increased expression of CD137 by CD8+ TCM in recovered mild patients. Thus, the presence of CD4+ and CD8+ T cell subsets against SARS-CoV-2 in individuals recovered from COVID-19 was evidenced here. Among these, the TEM, TCM, and TEMRA subtypes of CD8+ T cells stood out as the most effective in promoting viral clearance in the context of antigenic reexposure. While naive cells, as well as CD4+ memory T cell subsets, have an immunomodulatory potential capable of guaranteeing patients recovered from COVID-19 the ability to respond in a coordinated and balanced way to the inflammation caused by SARS CoV-2 in the process of reinfection, promoting virus control without causing irreversible tissue damage in mild and severe recovered patients.
  • LARISSA MARIA FERREIRA COITINHO
  • EVALUATION OF THE USE OF LITERATURE AS A TEACHING AND LEARNING STRATEGY OF HUMAN PHYSIOLOGY IN UNDERGRADUATION.
  • Fecha: 28-feb-2023
  • Hora: 14:00
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  • The interdisciplinary nature of physiology makes understanding its concepts a challenge for students. It is important to encourage the development of new methodological strategies that help and facilitate the teaching and learning of physiology. In this context, we started the project PhysioArt Once upon a time..., which proposes the interaction between physiology and literature to awaken students' interest in learning and understanding physiological concepts and mechanisms, suggesting to undergraduates that they reinterpret classic tales from literature incorporating in their reinterpretations physiological concepts. n=60 students participated in this activity, who, as a group, reinterpreted short stories by Edgard Allan Poe in the context of Physiology of the respiratory system in semester 2021.2 and stories by Machado de Assis in the context of the endocrine system in semester 2022.1. After the activity, the students voluntarily answered an evaluation questionnaire about PhysioArt Once upon a time..., where the answers varied on a scale from 0 to 5, where 0 means not at all and 5 means a lot. Our results suggest, considering the score between 3-5, that 81.7% of the students who participated in the activity FisioArte Era uma vez... consider the subject of human physiology difficult and 80% agree that the work of reinterpreting the short story facilitated the understanding of the concepts and mechanisms of human physiology. Furthermore, the results showed that 90% agreed that PhysioArt Once upon a time... increased the interest in learning physiology in a more exciting and enjoyable way. We also observed that 58.4% of the students agreed that this activity involving literature, physiology and group work helped to reduce the stress of the other activities they were performing. The evaluation of these students was carried out through the average score of the short story activity and the score of the dissertation test, which made the average in each of the modules higher than the averages of the tests of the previous semesters (2018.2 and 2019.2). In addition, considering only the grades of the dissertation tests, the endocrine physiology averages of the students who participated in the short story activity were higher than the average of the previous semesters. Our results suggest that PhysioArt Once upon a time... is an efficient pedagogical tool in the teaching-learning process of physiology, as it encourages students to teach and learn physiology, as well as being an efficient alternative method of learning assessment.
2022
Descripción
  • PEDRO HENRIQUE DE SOUSA PALMEIRA
  • EVALUATION OF REGULATORY T LYMPHOCYTES IN CONVALESCENT COVID-19 PATIENTS
  • Fecha: 30-sep-2022
  • Hora: 09:00
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  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), causes a range of clinical symptoms that can lead to death. Although several studies have demonstrated the pivotal role of the host immune system in the development of distinct clinical profiles, many questions still remain. In the present study, comparative analyses in Regulatory T cells (Treg) of the volunteers not previously infected with SARS-CoV-2 (HC) and volunteers who recovered from mild (Mild Recovered) and severe (Severe Recovered) COVID-19 were performed. Peripheral Blood Mononuclear Cells (PBMC) from enrolled volunteers were stimulated with SARS-CoV-2 related peptides (Pool Spike CoV-2 and Pool CoV-2) or Staphylococcal enterotoxin B (SEB). Using a multicolor flow cytometric assay were reported higher levels of Treg frequency and expression of IL-10, IL-17, perforin, granzyme B, PD-1, and CD39+CD73+ coexpression by studied lymphocytes in Mild Recovered compared to Severe Recovered and/or HC groups in some SARS-CoV-2 related stimulus. Moreover, Mild Recovered unstimulated PBMCs also presented more frequency of Tregs and expression of IL-10 and granzyme B than HC, suggesting long- term immunomodulation after disease resolution. Compared to Pool CoV-2 stimuli, Pool Spike CoV-2 reduced the IL-10 while improving PD-1 expression by Tregs from Mild Recovered volunteers. Curiously, Pool Spike CoV-2 elicited a decrease in Tregs IL-17+ frequency in Severe Recovered. In HC, the expression of LAP and cytotoxic granules coexpression by Treg were higher in Pool CoV-2 stimulated samples suggesting an immunological cross-reactivity. In the present study, comparative analyses of the immunological data between Mild Recovered volunteers who experienced or did not experience some symptoms during the acute phase of COVID-19 were also performed. The main results showed that Pool Spike CoV-2 stimulus elicited a decreased pattern of Tregs IL-10+ and Tregs CTLA-4+ frequency in PBMC from volunteers who did not develop some symptoms. Moreover, higher levels of perforin and perforin+granzyme B+ coexpression by regulatory T cells were found in Mild Recovered volunteers who experienced dyspnea. Finally, were observed differential expressions of the ectonucleotidases CD39 and CD73 in Tregs between Mild Recovered volunteers that experienced musculoskeletal pain. Collectively, this study suggests that changes in immunosuppressive tools of Tregs could influence the development of a distinct COVID-19 clinical profile. Considering the comparative data of the Mild Recovered group, this work revealed a possible modulation at the Treg level that could help in the establishment of mild disease, thus having a great potential to contribute to the scientific efforts in understanding COVID-19 immunity.
  • MÁRCIA DANTAS DOS SANTOS
  • Avaliação do crescimento muscular e reprodutivo modulado pelo fotoperíodo da tilápia do Nilo (Oreochromis niloticus) durante todo o ciclo reprodutivo
  • Fecha: 28-jul-2022
  • Hora: 14:00
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  • Esse trabalho está estruturado em dois capítulos: artigo de revisão, com tópicos referentes a Aquicultura e fisiologia de teleósteos, com ênfase na tilápia do Nilo (Oreochromis niloticus); e estudo em sistema de cultivo intensivo de desempenho da tilápia submetida aos diferentes fotoperíodos, durante 180 dias. Os objetivos traçados foram: identificar os padrões de crescimento somático, crescimento muscular, mobilização energética e reprodução das tilápias ao longo de 180 dias submetidas a diferentes fotoperíodos. Para tanto, foi montado um sistema de recirculação com 9 caixas d`água de 1000L, sendo 3 caixas por fotoperíodo (T1 = 24h Claro: 0h Escuro; T2 = 18hC:06hE e T3 = 12hC:12hE). Embriões foram povoados em incubadoras, depois em berçários, e por último nas caixas d`água (n=142 animais/cada). As tilápias apresentaram performances variadas a depender dos fotoperíodos. A mortalidade foi considerável nos primeiros 15 dias de vida do animal com mortes significativas até os 30 dias com diferenças estatísticas (p<0,0001 e p<0,0001, respectivamente). Os menores resultados de mortalidade foram identificados no T1. Quanto à massa corporal, diferenças estatísticas (p<0,004) foram registradas no dia 135 apresentando o T1 maior massa (56,57 ± 23,11g). Em relação ao comprimento total, houve diferenças estatísticas entre os tratamentos nos dias 135 (p<0,002) e 180 (p<0,016) pós-eclosão. O T1 apresentou os maiores comprimentos (14,85 ± 2,58 e 19,52 ± 2,99cm) em ambos os dias, respectivamente. No que tange ao ganho de massa, taxa de crescimento específico e fator de condição, não houve diferenças estatísticas entre os tratamentos. O crescimento do músculo esquelético apresentou uma tendência de aumento no comprimento da fibra ao longo dos dias, em especial do T1, caracterizando um crescimento predominantemente hipertrófico. Os animais desenvolveram, em todos os tratamentos, fibras maiores que 180µm de diâmetro, que começaram a ser identificadas a partir do dia 90. O glicogenio hepático apresentou diferenças estatisticas em função dos fotoperíodos nos dias 60, 90, 120 e 150 (p<0,002; 0,047; 0,001 e 0,001, respectivamente) com aumento na frequência de depósito de glicogênio no T1. Quanto aos estoques de lipídios, houve diferença estatística nos dias 150 e 180 (p<0,001 e 0,003, respectivamente) entre os tratamentos. O T3 obteve maior frequência de acúmulo hepático de lipídios. No que corresponde a determinação do sexo, foi identificada uma porcentagem de inversão sexual de 85,7% para machos fenotípicos e 14,3% intersexo para todos os tratamentos. Não houve potencialização pelo fotoperíodo na inversão sexual induzida pela suplementação de testosterona na alimentação. No dia 90, foram identificadas células germinativas de espermatozóides em fase indiferenciada e em processo de diferenciação. Nesse sentido, descrevemos os dados só a partir do dia 120. A partir deste período os peixes se encontraram em maturação, em razão de apresentarem as maiores porcentagens dos cistos de espermatozóides no dia 150 (T1-26% T2-53% e T3-37%) com menor porcentagem para o T1. No dia 180, os espermatozoides mostraram menores taxas em relação ao dia 150 (T1-23% T2-27% e T3-32%). Nesse último dia é possível sugerir, pelos dados decrescentes, que os animais estão entrando na fase de regressão. O presente estudo revelou que o fotoperíodo de T1 proporciona melhores resultados na criação de tilápia do Nilo, no que se refere ao desempenho produtivo. Quanto aos parâmetros de maturação sexual o T1 apresentou menores percentuais de maturação.
  • LARISSA SUELEN DA SILVA LINS
  • Flavonoids are bioactive polyphenols known to present, for the most part,
  • Fecha: 29-abr-2022
  • Hora: 09:00
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  • Flavonoids are bioactive polyphenols known to present, for the most part, cardioprotective action, being effective in the treatment of cardiovascular diseases such as arterial hypertension. In this work, some effects induced by the flavonoids flavone (FVN), 3-hydroxyflavone (3FVN) and 5-hydroxyflavone (5FVN) were verified in normotensive rats, using in silico, ex vivo, and in vivo approaches. In ex vivo experiments, we evaluated the relaxing effect promoted by FVN, 3FVN or 5FVN in the isolated superior mesenteric artery of rats pre- contracted with phenylephrine (Phen 10 μM). In order to investigate the mechanism of action of 5FVN, other experimental protocols were used, such as pre-contraction of the rings with 60 mM and 20 mM KCl depolarizing solutions, and the incubation of the rings in the presence of ion channel blockers, glibenclamide (1mM) and 4-aminopyridine (10 µM). Then, through in vivo experiments, it was possible to analyze the physiological effect induced by the acute intravenous administration of different doses of 5FVN on blood pressure and heart rate of non-anesthetized rats. The in silico results demonstrated a series of potential beneficial cardiovascular activities associated with the compounds, such as vasodilator, antioxidant and cardioprotective action. The ex vivo protocols demonstrated that the compounds FVN, 3FVN and 5FVN showed concentration-dependent vasorelaxant activity in rings pre-contracted with FEN. Removal of the endothelium did not alter the effect induced by the compounds. When comparing pD2 values, it was observed that 5FVN was the most potent in promoting vasorelaxation, when compared to 3FVN and FVN, both in rings with intact endothelium and in rings whose endothelium was removed. Therefore, 5FVN was chosen for future analyses. The vasodilatory effect of 5FVN was attenuated when vascular rings were pre-contracted with 60 mM KCl compared to pre-contracted with PHE in the absence of functional endothelium. The incubation of the rings with KCl 20 and glibenclamide was not able to change the 5FVN concentration response curve compared to the control group, since in the presence of 4-aminopyridine there was a significant attenuation in the 5FVN response and, therefore, we suggest that the effect of Compound occurs through Kv channels. Acute intravenous administration of doses 1mg/kg; 5mg/kg; 10mg/kg and 20mg/kg of 5FVN caused hypotension and tachycardia in non-anesthetized normotensive rats. It is concluded that, among the flavonoids analyzed, 5FVN has the greatest potency in exerting vasorelaxation in superior mesenteric artery rings of normotensive rats. The relaxation induced by this compound is independent of the functional endothelium and involves voltage-gated K+ channels (Kv) present in vascular smooth muscle. 5FVN-induced vasodilation likely contributes to the hypotension observed in non-anesthetized normotensive rats.
  • RAYANE MARIA PESSOA DE SOUZA
  • Effects of treatment on hypertension with Cannabis Extract rich in cannabidiol cardiovascular modulation with renovascular hypertension.
  • Fecha: 20-abr-2022
  • Hora: 09:00
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  • Cannabis sativa (CS) is one of the most used plants since antiquity. currently its medicinais use is released in Brazil, from which phytocannabinoid derivatives are derived, such as cannabidiol (CBD) which has neuroprotective, anti- inflammatory and antioxidant effects. Some studies suggest that CS-derived CBD may influence the cardiovascular system. In this work, cardiovascular of the Cannabis Extract rich in cannabidiol (CECBD) were analyzed in renovascular. hypertensive (2K1C). For this, Wistar rats were submitted to 2K1C or SHAM surgeries. After, They were treated with CECBD by gavage (twice a day, during 14 days). Our results, showed that chronic CECBD treatment decreases MAP in 2K1C rats (2K1C+CECBD: 138,7 ± 9,6 vs.2K1C: 170,8 ± 7,5 mmHg) but did not change baseline HR. The CECBD treatment also improved baroreflex sensitivity (2K1C+CECBD: -2,1 ± 0,1 vs. 2K1C: -1,8 ± 0,06 bpm.mmHg-1), as well as reduced hypotensive response induced by ganglionic blockade in 2K1C+CECBD animals (2K1C+CECBD: ∆-50,0 ± 3,4 vs. 2K1C: ∆-92,5 ± 13,4 vs. mmHg). However, CECBD treatment did not change cardiovascular chemoreflex responses. Our results suggested that CECBD has an important hypotensive effect in renovascular hypertensive rats (2K1C model).
2021
Descripción
  • ATALIA FERREIRA DE LIMA
  • Study of medulla and hypothalamic astroglial glutamatergic mechanisms in cardiovascular modulation in rats with renovascular hypertension
  • Fecha: 26-nov-2021
  • Hora: 14:30
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  • Astrocytes modulate neuronal activity through different mechanisms, including reuptake of neurotransmitters from the environment extracellular. It is known that in renovascular hypertension (HRv) there is an increase in release of glutamate by neurons of bulbar nuclei involved with cardiovascular modulation, contributing to the increase in the activity of presympathetic neurons. However, little is known about the participation of astrocytes in the reuptake and conversion of glutamate in the bulb region of rats hypertensive The aim of this study was to analyze the participation of astrocytes in the reuptake and recycling of glutamate in the bulb of rats with HRv. For Therefore, we performed the implantation of a guide cannula in the intracisternal region (ICM) from normotensive and HRv rats (by the 2Rins-1Clipe / 2K1C model) for the performance of microinjections: a) of the Inhibitor of the transporter of astrocytic glutamate GLT1 [DHK (1 mM)], b) the glutamine synthetase inhibitor [L-AAA (2 mM)] and c) gliotoxin fluorocitrate [FCt (0.2 mM)]. One group of animals with HRv was treated with Losartan (AT1 antagonist) for gavage at a dose of 30mg/kg/day for 4 weeks after the period of stabilization of the hypertensive condition. For in vitro studies, we performed, for through the western blotting technique, the analysis of protein expression of the astrocytic cytoskeleton - glial fibrillary acid protein - (GFAP), of the reuptakers of glutamate (GLT1 and GLAST) and the enzyme glutamine synthetase (GS) from subfornical organ (SFO) regions, paraventricular nucleus of hypothalamus (PVN), rostral ventrolateral medulla (RVLM), solitary tract nucleus (NTS) and Cortex. Our results showed that inhibition of the transporters of astrocytic glutamate with DHK or inhibition of the GS enzyme with L-AAA ICM did not promote significant cardiovascular changes among the animals from the SHAM groups, 2R1C and 2R1C/LOS. However, inhibition of the activity of glia with FCt ICM promoted a significant increase in mean arterial pressure (PAM) from 2K1C animals, but not from SHAM or 2K1C/LOS animals. THE analysis of protein expression in the bulb showed that hypertensive animals showed reduced expression of GLT1 and GLAST transporters in the RVLM, as well as reduced expression of GFAP and GS in NTS and However, little is known about the participation of astrocytes in the reuptake and conversion of glutamate in the bulb region of rats hypertensive The aim of this study was to analyze the participation of astrocytes in the reuptake and recycling of glutamate in the bulb of rats with HRv. For Therefore, we performed the implantation of a guide cannula in the intracisternal region (ICM) from normotensive and HRv rats (by the 2Rins-1Clipe / 2K1C model) for the performance of microinjections: a) of the Inhibitor of the transporter of astrocytic glutamate GLT1 [DHK (1 mM)], b) the glutamine synthetase inhibitor [L-AAA (2 mM)] and c) gliotoxin fluorocitrate [FCt (0.2 mM)]. One group of animals with HRv was treated with Losartan (AT1 antagonist) for gavage at a dose of 30mg/kg/day for 4 weeks after the period of stabilization of the hypertensive condition. For in vitro studies, we performed, for through the western blotting technique, the analysis of protein expression of the astrocytic cytoskeleton - glial fibrillary acid protein - (GFAP), of the reuptakers of glutamate (GLT1 and GLAST) and the enzyme glutamine synthetase (GS) from subfornical organ (SFO) regions, paraventricular nucleus of hypothalamus RVLM. In the hypothalamic region, we observed a reduction in protein expression of the GLAST transporter in the SFO and increase in the expression of GFAP in the PVN of hypertensive animals. Our results showed that transporters of astrocytic glutamate and the GS of the bulbar surface appear not to be involved with the cardiovascular modulation of normotensive animals or with HRv. However, glia seem to be involved in MAP modulation in this pathophysiology. In addition, our in vitro studies showed changes in protein expression of different markers of astrocytic activity in bulbar (NTS and RVLM) and hypothalamic (SFO and PVN) nuclei of animals with HRv. In this sense, our studies suggest the participation of cells in the glia in the modulation of blood pressure in HRv, however additional studies, to better understand the participation of astrocytes on cardiovascular modulation in hypertensive rats.
  • ATALIA FERREIRA DE LIMA
  • “Astroglial glutamatergic mechanisms study of the brainstem and hypothalamus in cardiovascular modulation in rats with renovascular hypertension”
  • Fecha: 26-nov-2021
  • Hora: 14:00
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  • Astrocytic cells modulate neuronal activity, including glutamate uptake from the extracellular environment. In renovascular hypertension (HRv) there is an increase in released glutamate by neurons in brainstem nuclei involved in the cardiovascular modulation, contributing to increasing pre-sympathetic neurons activity. However, it is not clear about the involvement of the astrocytes in the extracellular glutamate uptake and recycling in hypertension. This study aimed to analyze the astroglial participation in the uptake and glutamate recycling in the brainstem and hypothalamus in HRv rats. For this purpose, we performed guide-cannula implantation intracisterna magna (ICM) in SHAM and 2K1C rats (HRv model) for microinjections of: a) astrocytic glutamate transporter EAAT2 / GLT1 inhibitor [DHK (1mM)], b) astrocytic glutamine synthetase inhibitor [L-AAA (2mM)] and c) gliotoxin fluorocitrate [FCt (0.2mM)]. One group of animals (2K1C/LOS) was treated with Losartan (AT1 antagonist) by gavage at a dose of 30 mg/kg/day for 4 weeks. After femoral artery catheterization, we made cardiovascular measurements. For in vitro studies, we analyzed by western blotting the astrocytic cytoskeleton - glial fibrillary acid protein - (GFAP), the glutamate receptors (EAAT2 / GLT1 and EAAT1 / GLAST) and the enzyme glutamine synthetase (GS) protein expression. into subfornical organ (SFO), paraventricular nucleus (PVN), rostral ventrolateral brainstem (RVLM), solitary tract nucleus (NTS) and cortex (control area) regions. Our results showed that DHK, or L-AAA ICM microinjection did not change baseline MAP (mmHg) or HR (bpm) in SHAM, 2K1C or 2K1C/LOS groups. FCt ICM microinjection promoted an increase in MAP (mmHg) in the 2K1C group, but not SHAM or 2K1C/LOS. The western blotting analysis showed t in the RVLM a reduction in the GLT1 / EAAT2 and GLAST / EAAT1 transporters expression in the 2K1C. There was also a decrease in the GFAP and GS expression into NTS and RVLM of 2K1C rats. In addition, we observed a reduction in the GLAST / EAAT1 transporter expression into SFO and an increase in GFAP expression into PVN of 2K1C animals. Our results showed that inhibition of astrocytic glutamate transporters or GS on bulbar surface does not seem to be involved in the cardiovascular modulation in normotensive or HRv rats. However, glia appears to be involved with BP modulation in HRv. Furthermore, our in vitro studies showed HRv induce changes in the expression of different astrocytic protein in the brainstem hypothalamic nuclei involved with the cardiovascular modulation. In that regards, our studies suggest the involvement of glial cells in the modulation of blood pressure in HRv. However further studies are needed to better understand the participation of astrocytes to modulate cardiovascular function in hypertensive rats.
  • GEORGIANNA DE ARAUJO HENRIQUES FERREIRA
  • EFFECTS OF THE INTERVENTION WITH PROBIOTIC FORMULATION OF Lactobacillus fermentum ABOUT INTESTINAL MICROBIOTA AND PARAMETERS CARDIOMETABOLICS IN ADULT RATS
  • Fecha: 25-ago-2021
  • Hora: 14:00
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  • Among the non-communicable chronic diseases (NTCD), Systemic Arterial Hypertension (SAH) presents dyslipidemia as a risk factor. With regard to blood pressure regulation, it seems that dyslipidemic conditions deregulate some blood pressure control centers, which can generate persistent peaks of high blood pressure. The appearance of SAH after exposure to dyslipidemia is associated with qualitative and quantitative changes in the intestinal microbiome, presenting characteristics of dysbiosis. In this sense, intestinal dysbiosis develops concomitantly with increased oxidative stress and development of hypertension. Knowing the therapeutic potential of administering probiotics in SAH, this study investigated the effects of administering a probiotic formulation of Lactobacillus fermentum (L. fermentum: strains 139, 263 and 296) on cardiorespiratory and metabolic parameters and changes in the intestinal microbiome of rats at 90 days exposed to dyslipidemia. Wistar rats (n=18) adults aged 90 days were fed either a control diet (CTL) or a high fat diet (HFD). The animals were divided into 3 groups: control group (CTL: n=6); high-fat diet + probiotic formulation of Lactobacillus fermentum 139, 263 and 296 (HFD-LF: n=6); high fat diet group (HFD: n=6). The administration of L. fermentum strains (109 CFU/mL of each strain) was performed daily via gavage from the 90th to the 120th day of life. On the 120th day of life, feces were collected for analysis of fecal microbiota, blood samples were quantified total cholesterol (TC), high-density lipoprotein (HDL- cholesterol), low-density lipoprotein (LDL-cholesterol), triglycerides ( TG) and insulin tolerance test (TII). Cardiovascular parameters were obtained from the recording of blood pressure (BP) and heart rate (HR) at baseline levels and after administration of phenylephrine (2mg/kg; 4mg/g; 8mg/kg) and sodium nitroprusside (10mg/kg) ; 20mg/kg; 25mg/kg) to assess baroreflex and hexamethonium (25mg/kg) to assess the contribution of sympathetic tone. The variability of HR and BP was evaluated under baseline conditions. The HFD-LF group had lower serum levels of TG, TC and LDL-cholesterol, higher plasma concentration of HDL-cholesterol and smaller area under the TII curve after receiving the treatment with the probiotic formulation of L. fermentum for 4 weeks, when compared to the HFD group (p<0.05). BP levels were lower in the HFD-LF group compared to the HFD group (p<0.05), but without any change in HR (p>0.05). In the spectral analysis, the probiotic formulation with L. fermentum offered to the HFD-LF group prevented an increase in LF oscillations of the systotic blood pressure (SAP) and the LH/HF ratio of the cardiac interval (p<0.05) compared to the HFD group. However, the treatment did not interfere in HF oscillations and in the spontaneous sensitivity of the barroflex in comparison to the HFD group (p>0.05). After administration of hexamethonium, the increase in vasomotor tone was prevented in animals from the HFD-LF group compared to the HFD group (p<0.05). Considering the composition of the intestinal microbiota, the high-fat diet increased the relative abundance of bacteria from the phylum Firmicutes (Ruminococcaceae, Clostridiales, Christensenellaceae, Erysipelotrichaceae), the phylum Actinobacteria (Collinsella) and the phylum Proteobacteria (Helicobacter) of the HFD group compared to group CTL and after the administration of L. fermentum a lower relative abundance of these bacterial groups was found. In the HFD group, lower abundance of several families Ruminococcaceae, Lachnospiraceae, Erysipelotrichaceae, Eubacterium was found compared to the CTL group, but treatment with L. fermentum was not able to increase their relative abundance in the treated group (HFD+LF). Treatment with L. fermentum probiotic formulation attenuates dyslipidemia, insulin resistance, sympathetic hyperactivity and changes the intestinal microbiota pattern of adult rats exposed to a high-fat diet.
  • FABIANA GÓES BARBOSA DE FREITAS
  • THE IMPACT OF EXTRACORPOREAL CIRCULATION TIME IN THE IMMEDIATE POSTOPERATIVE PERIOD OF REVASCULARIZATION OF THE MYOCARDIUM
  • Fecha: 27-jul-2021
  • Hora: 14:00
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  • Cardiac surgery is a important intervention to decrease morbidity and mortality due to cardiovascular diseases that have low probability of cure, with myocardial revascularization being the most frequently surgery. This procedure aims to reduce symptoms caused by obstruction of coronary arteries, prolonging the life of the individual. The use of cardiopulmonary bypass is been the “gold standard” for these surgeries however, it can trigger deleterious effects to the body, such as: the systemic inflammatory response, myocardial depression, coagulopathies, hemodynamic instability and pulmonary dysfunction. Thus, the objective of this study was to evaluate cardiopulmonary bypass impact into profile of hemodynamic and biomarkers in patients undergoing myocardial revascularization surgery in different times. Were analyzed 153 patients that underwent myocardial revascularization surgery analyzed in a hospital in João Pessoa, were after being divided into 3 groups according to the cardiopulmonary bypass time: Group 0-60 (from 0 to 60 minutes), group 61-90 (from 61 to 90minutes) and group 90+ (above 90 minutes).We verified, the variables that were taken during the imediate postoperative period, s uch as: mean arterial pressure, heart rate leukocytes, hemoglobin, glycemia , creatinine, extubation time, arterial blood gas analysis and central venous pressure. We observed that the profile of patients is predominantly male, mean of ages 63,06 ± 9,41 years, high blood pressure and elderly. Based on our data, there was not correlation between CPB time and hemodynamic parameters like heart rate and pressures. The same was found with ventilatory and oxygenation parameters. A negative correlation was found between CPB time and HCO3 (r=-0,2576; p=0,0013) and base excess (r=-0,2940; p=0,0002). None correlation with leukocytes were find. Still, was observed differences in the levels of hemoglobin ((r=- 0,3608; p<0,0001) and glycemia (r=0,1714; p=0,0400) between group 1 and 3. Regarding extubation time, it was observed that individuals with shorter cardiopulmonary bypass time presented extubation more frequently in the operating room than the others. The cardiopulmonary bypass time had impact into acid-base balance, blood glucose, hemoglobin and extubation time of patients undergoing myocardial revascularization surgery, directly influencing the homeostasis of these individuals. Although the duration of the use of cardiopulmonary bypass is not the only one responsible for the appearance of complications, the data obtained so far demonstrate the importance of a multidisciplinary team in the immediate postoperative period, such as doctors, nurses and physicaltherapists, in order to reduce the chances of complications and their effects on the morbidity and mortality of these patients.
  • MICAELLE OLIVEIRA DE LUNA FREIRE
  • Probiotic formulation of Lactobacillus fermentum attenuates dyslipidemia, inflammation and oxidative stress in rats fed a high-fat diet.
  • Fecha: 07-jun-2021
  • Hora: 13:00
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  • The imbalance of the intestinal microbiota (IM) induced by a high fat diet has been associated with the development of cardiometabolic disorders. Some studies have demonstrated possible methods for maintaining IM homeostasis, with administration with probiotics being one of the choices for using non-pharmacological intervention. These compounds are known to contribute to the health of the host, through their hypocholesterolemic, anti-inflammatory and antioxidant properties, and can be a promising strategy for the treatment of metabolic and cardiovascular diseases. The present study aimed to investigate the effects of oral administration of a probiotic formulation containing Lactobacillus fermentum 139, 263 and 296 on the biochemical parameters, inflammation and oxidative stress in rats fed a high-fat diet. The rats were divided into three experimental groups: control group (control diet + placebo), HFHC group (diet rich in lipids and cholesterol + placebo), and group HFHC + Lf (diet rich in lipids and cholesterol + L. fermentum 139, 263 and 296). These groups were submitted to supplementation with placebo solution or L. fermentum 139, 263 and 296, for 4 weeks, twice a day. The evaluation of body weight and food consumption occurred throughout the experiment, and after 4 weeks of supplementation, serum, colon and heart tissues and feces were collected to perform: measurement of serum lipid profile and inflammatory cytokines, quantification of acids organics and sugars in animal feces, in addition to evaluation of malondialdehyde (MDA) and activity of antioxidant enzymes and total thiol groups in colon and heart tissues. The results of the present study demonstrated that supplementation improved body weight and food consumption when compared to the HFHC group. The HFHC-Lf group showed a reduction in serum levels of total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides (TG), and a reduction in high-density lipoprotein (HDL), in addition to reducing atherogenic indices when compared to dyslipidemic group. Administration with L. fermentum 139, 263 and 296 reduced IL-1β and increased IL-10. The administration with L. fermentum 139, 263 and 296 contributed to the increase in raffinose in the feces, but without significant changes in fructose and short-chain fatty acids. In addition, supplementation with L. fermentum 139, 263 and 296 was able to reduce MDA concentrations and increase superoxide dismutase (SOD), glutathione-S-transferase (GST) and total thiol groups in the colon, and promote increased catalase activity (CAT), GST and amount of total thiol groups in cardiac tissues. Therefore, these results indicate the potential effects promoted by L. fermentum 139, 263 and 296 on biochemical parameters, in addition to the anti-inflammatory and antioxidant properties of these probiotic strains, which can be used as possible therapeutic agents in cardiometabolic disorders.
  • ALYNNE CARVALHO GALVÃO
  • Evaluation of the effects induced by carboxymethyl-glucan (CM-G) on the cardiovascular system of normotensive and hypertensive rats.
  • Asesor : VALDIR DE ANDRADE BRAGA
  • Fecha: 11-may-2021
  • Hora: 14:30
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  • Hypertension is a highly prevalent disease worldwide, being characterized by a multifactorial clinical condition. In this context, this study study was designed to investigate the effects of a newly synthesized carboxymethyl-glucan (CM-G) on blood pressure (BP), baroreflex sensitivity (BRS) and sympathetic vascular modulation in renovascular hypertensive rats. Male Wistar rats were divided into four groups: SHAM+SALINE, 2K1C+SALINE (subjected to renal artery clipping to induce renovascular hypertension); SHAM+CM-G (treated with CM-G) and 2K1C+CM-G (treated with CM-G). The daily treatment with CM-G (40 mg/kg) was performed for 2 weeks. Blood pressure, heart rate (HR), systolic BP variability, baroreflex sensitivity (BRS) and sympathetic vascular tone were evaluated. After six weeks of renal artery clipping, 2K1C rats exhibited arterial hypertension (171 ± 11 vs. 118 ± 4 mmHg, p < 0.05), impaired BRS (−1.30 ± 0.10 vs. −2.59±0.17 bpm.mmHg-1, p < 0.05) and enhanced sympathetic activity by 81% when compared to sham rats. Oral administration of CM-G in renovascular hypertensive rats reduced hypertension (126 ± 4 vs. 171 ± 11 mmHg, p < 0.05) and improved the BRS (−2.03±0.16 vs. −1.30 ± 0.10 bpm.mmHg−1, p < 0.05) in 2K1C rats when compared to placebo. Those effects seem to be caused by a reduction in sympathetic activity. Besides, hypertensive rats have greater contraction to phenylephrine (126.60% ± 2.97% vs. 95.24% ± 5.49%; p < 0.05), which was restored by CM-G treatment (90.26% ± 8.54%vs. 95.24% ± 5.49%; p > 0.05). Furthermore, vasorelaxation to acetylcholine and sodium nitroprusside was diminished in hypertensive rats, which was also restored by CM-G. Finally, oral treatment with CM-G reduced serum levels of malondialdehyde, an important biomarker used in the assessment of oxidative stress, in treated hypertensive animals when compared to untreated animals (14.62 ± 0.93 vs. 21.82 ± 1.27 nmol/ml, p ˂ 0,05). The present study revealed for the first time that treatment with CM-G reduced arterial hypertension and restored baroreflex sensitivity through a reduction in sympathetic tone, in addition to normalizing vascular reactivity and reducing oxidative stress in rats with renovascular hypertension.
  • LUCAS RANNIER RIBEIRO ANTONINO CARVALHO
  • Effects of consumption of inorganic nitrate (NaNO3) on the longevity and aging of Wistar rats.
  • Fecha: 31-mar-2021
  • Hora: 09:00
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  • The search for interventions and drugs that increase longevity and decrease the effects of time on the organism (aging), is as old as humanity itself. Based on recent descriptions of the beneficial effects of nitrates on various health conditions, the consumption of vegetables rich in this salt, such as spinach and beet leaves, has been encouraged. However, the chronic effects of this supplementation have not yet been described and, due to its toxic potential, long-term evaluations are urgent and necessary. Therefore, the objective of this work was to evaluate the effects of sodium nitrate consumption on the longevity and aging of elderly rats. For that, Wistar rats of both sexes, 15 months old, were used, continuously supplemented with drinking water (placebo) or sodium nitrate solution (NaNO3 - 10mM), until natural death by senescence. During the treatment period, the animals were submitted to weekly clinical follow-ups and laboratory tests every three months. After death, vascular reactivity was evaluated and samples were collected for histopathological analysis and determination of the cause of death. The results show that supplementation with inorganic nitrate, for long periods, does not alter the life span and aging of individuals. In addition, chronic consumption was responsible for a significant improvement in the effect and sensitivity of vasoconstrictor and vasodilator substances, suggesting a significant improvement in vascular function, with no evidence of tolerance. In the laboratory follow-up, no changes caused by nitrate, regardless of gender, were shown, only changes related to healthy aging. Similar to the diagnosis of the cause of death, in which alterations caused by aging have been described in almost all organic systems, however, there were no significant differences between groups. Thus, it was possible to conclude that long-term supplementation with inorganic nitrate does not significantly interfere with the life span and healthy aging process. Suggesting that it is a safe and easily accessible intervention for long-term consumption. However, its effects appear to be dose-dependent and studies that assess its cost-benefit are needed.
  • MICKAEL SOUSA DA LUZ
  • Evaluation of the effect of borneol on the autonomic modulation of blood pressure in normotensive rats and with renovascular hypertension.
  • Fecha: 26-feb-2021
  • Hora: 14:00
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  • Borneol is a bicyclic monoterpene extracted from essential oils from different medicinal plants. This compound has been used for a long time in traditional Chinese medicine with promising cardiovascular effects. Some studies have demonstrated the antioxidant, vasodilator and antihypertensive potential of borneol in normotensive animals and with L-NAME hypertension, however nothing has been reported about its effects on renovascular hypertension, as well as on the autonomic modulation of blood pressure and its control mechanisms . The present study aimed to evaluate the effects induced by borneol on cardiovascular parameters of normotensive rats and renovascular hypertension. For this, a combination of protocols in vivo was performed on SHAM and 2R1C rats, thus evaluating the effect of oral treatment for 14 days with borneol on blood pressure, heart rate, sympathetic and parasympathetic autonomic activity and baroreflex sensitivity. Oral treatment with borneol was able to reduce blood pressure only in 2R1C rats (2R1C: 169.43 ± 9 vs. 2R1C + borneol: 123.12 ± 6 mmHg, p <0.05), as well as decreased blood pressure systolic (2R1C: 196 ± 11.39 vs. 2R1C + borneol: 144 ± 5.3 mmHg) and diastolic (2R1C: 154.9 ± 4.6 vs. 2R1C + borneol: 103.1 ± 4.5 mmHg) . The treatment did not cause significant changes in heart rate. When assessing autonomic function, borneol did not induce changes in parasympathetic activity, however, it was able to reduce sympathetic hyperactivity in 2R1C rats (2R1C: (-73.43 ± 4.969 vs. 2R1C + borneol: -48.52 ± 7.289 mmHg , p <0.05) Additionally, it also reduced the low frequency bands - LF (2R1C: 9.16 ± 0.52 vs. 2R1C + borneol: 3.59 ± 0.68 mmHg2, p <0.05) , without showing alteration in the high frequency bands - HF and sympathovagal index (LF / HF). Finally, oral treatment with borneol improved the sensitivity of pharmacologically induced baroreflex with vasoactive agents (2R1C: -1.3 ± 0.1 vs. 2R1C + borneol: -3.6 ± 0.3 bpm.mmHg-1, p <0.05), as well as in spontaneous baroreflex (2R1C: -1.38 ± 0.1 vs. 2R1C + borneol: - 3.56 ± 0.64 bpm.mmHg-1, p <0.05). These previous data suggest an antihypertensive effect of borneol, since it reduced blood pressure only in rats with renovascular hypertension. This effect may be related, in part, with its vasorelaxing activity and its ability to reduce sympathetic activity. This information associated with the improvement in baroreflex sensitivity makes borneol a molecule with an important future in hypertension therapy.
2020
Descripción
  • LUDMILLA CHRISTINE SILVA DE SALES
  • EFFECTS OF LINSEED OIL SUPPLEMENTATION ON OXIDATIVE STRESS AND MUSCLE INJURIES INDUCED BY ACUTE PHYSICAL EXERCISE.
  • Fecha: 14-dic-2020
  • Hora: 14:00
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  • Performing high intensity or exhaustive physical exercises can increase the likelihood of muscle injuries and chronic fatigue due to excess free radical production, which can cause muscle damage followed by inflammatory process and impairment in muscle function. Flaxseed (Linum usitatissimim L.) has antioxidant and anti-inflammatory effect, and the oil extracted from its seeds stands out for containing a higher concentration of omega-3 when compared to other vegetable oils. It is recognized that supplementation with omega-3 fatty acid can stimulate the body's antioxidant defenses and the reduction of pro-inflammatory markers. Therefore, our objective is to investigate the effect of flaxseed oil supplementation on oxidative stress and muscle injuries induced by physical exercise. Twenty male subjects, aged 18 - 39 years, physically active and who do not have chronic non-communicable diseases. The subjects were randomly distributed into 03 groups: Group 01- Placebo + Exercise; Group 02- Flaxseed Oil (6g/day) + Exercise; Group 03 - Flaxseed Oil (12g/day) + Exercise. Supplementation was performed for 07 days. Participants were submitted to a running session on a treadmill for 40 minutes, consisting of 05 minutes of warm (4-5Km/h), 30 minutes with the intensity determined by the heart rate reached in 70-75% of VO2 maximum and 05 minutes of warm (4-5Km/h). We measured blood pressure, maximum heart rate, anthropometric variables (weight, height, waist circumference, body mass index (BMI) and body fat percentage] and biochemical parameters, and inflammatory as well as oxidative stress (glucose levels, lipid profile, lactic dehydrogenase, creatine kinase, and lipid peroxidation). Body composition, blood pressure and energy intake were similar between groups. Supplementation with 06g/day during 07 days of flaxseed oil reduced blood glucose when compared to the control group (p<0.05), however, this reduction was not observed in the group that received 12g/day of flaxseed oil. Total cholesterol, HDL and LDL levels were similar before and after the intervention. The markers of muscle injury and oxidative stress did not present alterations before, during and after the intervention, indicating that probably, the 40-minute exercise at the intensity of 70-75% of the maximum VO2 was not sufficient to promote exhaustion in the individuals and that supplementation with 06 and 12g/day flaxseed oil during one week does not result in modulation of serum concentrations of these markers.
  • EMMANUEL VERISSIMO DE ARAUJO
  • Efeitos da dislipidemia materna sobre os níveis de pressão arterial, controle cardiorrespiratório e parâmetros bioquímicos na prole de fêmeas.
  • Fecha: 31-ene-2020
  • Hora: 09:00
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  • A hipertensão arterial evidenciada em ratos adultos expostos a dislipidemia materna pode ser dependente do sexo. Neste trabalho, investigamos os efeitos da dislipidemia durante a gestação e lactação sobre parâmetros cardiorrespiratórios e metabólicos na prole fêmea. Ratas foram divididas em dois grupos: um recebeu dieta controle (CTL) e outro recebeu dieta dislipidêmica (DLP) durante a gestação e lactação. Parâmetros antropométricos e bioquímicos, foram realizados nos filhotes dessas ratas aos 30 e 90 dias de idade, tais como: peso e comprimento da prole, testes oral de tolerância à glicose (TOTG), tolerância à insulina (TTI), colesterol total (CT), lipoproteínas de alta (HDL), baixa (LDL), muito baixa densidade (VLDL), triglicerídeos (TG) e o malondialdeído (MDA). Além disso, parâmetros respiratórios, tais como frequência respiratória (FR), volume corrente (VT) e ventilação (VE), foram avaliadas por pletismografia de corpo inteiro durante um período basal e após ativação de quimiorreceptores respiratórios com mistura hipercápnica (7 % CO2). Aos 90 dias de idade, a pressão arterial (PA) e a frequência cardíaca (FC) foram mensuradas em condições basais e após administração de cianeto de potássio (KCN, 0,04%) para avaliação do quimiorreflexo periférico, e do hexametônio (30 mg/kg), para avaliação do tônus simpático. Finalmente, avaliamos a variabilidade da FC e PA em condições basais. O grupo DLP apresentou baixo peso ao nascer (P<0.05), porém sem diferi-lo na fase adulta. Aos 30 dias de idade, os níveis séricos de TG e CT estavam aumentados na prole DLP (P<0.05). As fêmeas DLP também apresentaram aumento na FR basal, e maior resposta ventilatória à hipercapnia comparado ao grupo CTL (P<0.05). Aos 90 dias, a prole DLP apresentou maior área sob a curva no TOTG e TTI em comparação ao grupo CTL. Em condições basais, a FR, VT, VE, foram semelhantes entre os grupos, mas a prole DLP apresentou uma resposta cardiovascular e ventilatória elevada à hipercapnia quando comparada ao grupo CTL (P<0.0001). Os níveis pressóricos das ratas DLP estavam elevados (P<0.05), mas sem alteração na FC. Na análise espectral, foi observado que o componente LF da PA sistólica e a razão LF/HF do intervalo cardíaco foram elevados no grupo DLP (P<0.05). Os desafios farmacológicos impostos pelo KCN, revelou maior resposta pressórica do grupo DLP (P<0.05), mas sem alterar o delta de FC. Após administração do hexametônio, as fêmeas DLP demonstraram uma tendência a tônus simpático (P<0.06). Esses achados foram combinados com elevados níveis séricos de MDA (P<0.05). A prole de ratas DLP apresentaram hipertensão arterial na vida adulta combinada com hiperatividade simpática e respostas ventilatórias e autonômicas amplificadas frente à hipóxia e hipercapnia.
  • FRANCINEIDE FERNANDES COSTA
  • Interação central entre óxido nítrico, lactato e as células da glia na modulação comportamental de ingestão de água e sódio em ratos
  • Fecha: 23-ene-2020
  • Hora: 09:00
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  • Estudos recentes do nosso laboratório mostraram que a glia da região dos órgãos circumventriculares (OCVs) participam da modulação do equilíbrio hidroeletrolítico. Há evidências de que o lactato produzido pelos astrócitos, por meio do mecanismo chamado “astrocyte-neuron lactate shuttle” (ANLS), participa da via inibitória de modulação da ingestão de sódio através da ativação de interneurônios GABAérgicos. Um outro neuromodulador dessa via inibitória é o óxido nítrico (NO), o qual promove um aumento na atividade de interneurônios GABAérgicos. Além disso, é conhecido que o NO atua no metabolismo energético astrocítico, inibindo a respiração mitocondrial e estimulando o consumo de glicose, resultando na produção e acúmulo de lactato nos astrócitos. Nesse contexto, a nossa hipótese é que o NO na região dos OCVs induz a liberação de GABA direta ou indiretamente via produção de lactato astrocítico. O GABA por sua vez, atuaria modulando a via tônica inibitória envolvida na modulação da ingestão de água e sódio. Para tanto, utilizamos ratos Wistar, que foram submetidos à cirurgia de estereotaxia para implante de cânula guia no ventrículo lateral (VL). Após a cirurgia, os animais foram alojados em gaiolas metabólicas individuais e adaptados à ingestão de sódio (NaCl 0,3M) durante 5 dias. Após, realizamos a microinjeção intracerebroventricular (icv) de salina estéril 0,9%; L-NAME (40 μg/0,5 μl- inibidor da óxido nítrico sintase); L-Lactato (2 μg/0,5 μl); α-CHCA (3 μg/0,5 μl-inibidor MCT4, um transportador de lactato astrocítico); oxamate (17 μg/0,5 μl-inibidor da LDH) ou fluorocitrato (FCt, 8 μg/0,5 μl-inibidor glial). Em um outro protocolo realizamos a microinjeção de salina estéril 0,9% e do α-CHCA (3 μg/0,5) em ratos após a privação hídrica (48h). Após as microinjeções, a ingestão de água e sódio foi mensurada aos 5, 15, 30, 60 e 120 minutos. Realizamos ainda um protocolo ex vivo, incubando o SFO de ratos por 1h à 37ºC em meio osmótico normal (145mM de Na+), hiperosmótico (170mM de Na+) e hiperosmótico na presença de L-NAME (500 µM), dosando em seguida a concentração de lactato da amostra. Os resultados mostraram que o L-NAME icv aumentou a ingestão de água e sódio, enquanto a inibição da glia com o FCt não alterou a ingestão de água ou sódio. Entretanto, a microinjeção prévia do FCt reduziu a ingestão de água e de sódio induzida pelo L-NAME. O L-Lactato icv não alterou a ingestão basal de água ou de sódio, mas aboliu a ingestão de água e de sódio induzidas pelo L-NAME. O bloqueio dos transportadores de lactato astrocíticos com o α-CHCA não alterou a ingestão basal de água ou de sódio, bem como a ingestão de água ou de sódio induzida pelo L-NAME. Por outro lado, nos animais submetidos à privação hídrica, o α-CHCA promoveu aumento na ingestão de água e sódio. Observamos ainda que a submissão do SFO ex vivo dos animais ao meio hiperosmótico promoveu aumento na concentração de lactato; em contrapartida, esse resultado não sofreu alteração na presença do L-NAME. Nossos resultados sugerem que há uma interação entre NO e as células da glia na modulação comportamental de ingestão de água e sódio em animais normohidratados. E que o mecanismo de transporte de lactato astrócito-neurônio (ANLS) na região dos OCVs parece estar envolvido na modulação da ingestão de água e sódio em condições de hipertonicidade do meio extracelular.
2019
Descripción
  • FRANCISCO ANTONIO DE OLIVEIRA JUNIOR
  • Efeitos da suplementação com óleo de coco em pacientes com hipertensão arterial de estágio 1
  • Fecha: 28-nov-2019
  • Hora: 09:00
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  • Mesmo considerando o avanço na farmacologia anti-hipertensiva e no conhecimento sobre os mecanismos subjacentes à hipertensão arterial sistêmica (HAS) conquistados ao longo do tempo, o impacto gerado pela HAS sobre a saúde segue em contínua ascensão. Como alternativa ao tratamento farmacológico tradicional, foi testada a hipótese que a suplementação alimentar com óleo de coco extravirgem (OCEV), isolada ou combinada ao treinamento físico aeróbio, poderia exercer efeito anti-hipertensivo em pacientes com hipertensão arterial de estágio 1. Para isso, 46 (quarenta e seis) voluntários hipertensos de ambos os sexos, com idade de 42,5 ± 11,7 anos foram divididos em dois grupos (treinado e não-treinado) e submetidos a um ensaio clínico placebo-controlado para avaliar os efeitos da suplementação com óleo de coco extravirgem (10ml/dia) por um período experimental de 30 dias. O estudo foi devidamente aprovado pelo Comitê de Ética e Pesquisa do Hospital Universitário Lauro Wanderlei (UFPB) sob parecer nº 1.523.128/2016. Após a triagem e recrutamento, os pacientes foram submetidos ao monitoramento ambulatorial da pressão arterial por 24 horas, avaliação da variabilidade da frequência cardíaca, coleta sanguínea para análise dos níveis séricos de colesterol total, HDL, LDL, triglicerídeos e glicose, malodialdeído e capacidade antioxidante total. Adicionalmente, foram realizadas análise nutricional, avaliação antropométrica e composição corporal. Os dados foram expressos como média e 95% do intervalo de confiança e tratados com teste t Student ou ANOVA mista com medidas repetidas, seguida de pós-teste de Bonferroni e p < 0,05. Os resultados indicam que, apesar de promover uma elevação da ingestão calórica em relação a suplementação com placebo (1861 kcal [IC 95% = 1656 – 2066] versus 1613 kcal [IC 95% = 1400 – 1826]; p = 0,03), os pacientes que foram suplementados com OCEV não apresentaram alterações significativas nas variáveis antropométricas e de composição corporal. Não foram observadas diferenças significativas entre os grupos em relação às concentrações séricas de colesterol total (F (1,41) = 0,924; p = 0,333 e η2 = 0,022); LDL (F (1,41) = 3,790; p = 0,058 e η2 = 0,085); HDL (F (1,41) = 1,562; p = 0,219 e η2 = 0,038); triglicerídeos (F (1,41) = 0,584; p = 0,440 e η2 = 0,014) e também não houve interação de efeitos relacionados ao tipo de suplementação e treinamento físico em função do tempo. No que diz respeito à glicemia, não houve efeito de OCEV (F (1,41) = 0,069; p = 0,795 e η2 = 0,002) nos grupos suplementados, embora os valores de glicemia tenham demonstrado um padrão diferente de modificação entre os pacientes suplementados com OCV e placebo ao longo do período experimental (F (1,41) = 5,020; p = 0,031 e η2 = 0,117). Não houve efeito sobre as concentrações séricas de MDA (F (1,41) = 0,391; p = 0,535 e η2 = 0,010) associado ao OCEV, isolado ou combinado ao treinamento aeróbio, mas, de maneira similar ao que ocorreu para glicemia, houve efeito da interação do tipo de suplementação utilizada ao longo do tempo (F (1,41) = 8,147; p = 0,007 e η2 = 0,169). Essa resposta não se refletiu na capacidade antioxidante total (F (1,39) = 0,544; p = 0,466 e η2 = 0,015). Não foram identificadas mudanças significativas sobre os níveis de pressão arterial sistólica (F (1,39) = 3,217; p = 0,081 e η2 = 0,078), diastólica (F (1,39) = 0,350; p = 0,558 e η2 = 0,009) e média (F (1,39) = 1,498; p = 0,228 e η2 = 0,038) em nenhum grupo após o período experimental. Por fim, os dados de variabilidade da pressão arterial não mostraram um efeito isolado do tratamento, mas ratificam o efeito da interação entre o tipo de suplementação em função do tempo: F (1,39) = 5,564, p =0,023, η2 = 0,125, λ = 0,875) em relação a PAM. Entretanto, essa resposta não foi confirmada pelos parâmetros de variabilidade da frequência SDNN (F (1,17) = 0,274; p = 0,608 e η2 = 0,017), RMSSD (F (1,17) = 0,946; p = 0,345 e η2 = 0,056), razão SDNN/RMSSD (F (1,17) = 1,449; p = 0,246 e η2 = 0,008) e SD2/SD1 (F (1,17) = 2,063; p = 0,170 e η2 = 0,114). Em conclusão, a suplementação com OCEV (10ml/dia) por um período de 30 dias, isolada ou combinada com treinamento físico aeróbio, não foi capaz de induzir efeitos terapêuticos sobre a hipertensão arterial de estágio 1 em humanos. Além disso, não demonstrou associação direta com a melhora do estresse oxidativo e da função autonômica dos pacientes hipertensos.
  • ERICKA GARCIA LEITE
  • AVALIAÇÃO DOS EFEITOS INDUZIDO PELO 2-NITRATO-1,3-DIBUTOXIPROPANO (NDBP) NA FUNÇÃO VASCULAR EM MODELO DE ATEROSCLEROSE
  • Fecha: 30-ago-2019
  • Hora: 14:00
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  • A aterosclerose é uma doença arterial crônica, de caráter inflamatório e fibroproliferativo que acomete milhares de pessoas ao ano sendo uma das principais causas de morte a nível mundial. A disfunção endotelial é uma das principais alterações detectáveis durante o desenvolvimento da aterosclerose. Caracterizada por vasodilatação prejudicada e aumento da resposta vasoconstritora, principalmente pela diminuição da biodisponibilidade de NO e perda da sinalização da via NO/GMPc/PKG. Experimentalmente, pode ser demonstrada por prejuízo do relaxamento dependente de endotélio à acetilcolina (ACh) e aumento da resposta de contração à fenilefrina (Fen). Os nitratos orgânicos vêm sendo utilizados há anos para tratamento de doenças cardiovasculares mimetizando o papel do NO endógeno. Porém, a utilização desses compostos a longo prazo resulta no desenvolvimento de tolerância. Neste estudo foi avaliado um nitrato orgânico sintetizado a partir da glicerina, o 2-nitrato-1,3-dibutoxipropano (NDBP). Com o objetivo de avaliar os efeitos do NDBP na função vascular em modelo de aterosclerose, utilizou-se camundongos machos, das linhagens C57BL/6 (CT) e nocautes para a apolipoproteína E (apoE-/-), os quais respectivamente receberam dieta padrão e dieta aterogênica Western Type (Rhoster, São Paulo, Brasil), contendo 41% de calorias em forma de lipídios e 1,5% de colesterol a partir de 8 semanas de vida, durante as 12 semana subsequentes. Os animais foram separados em 3 grupos: animais C57 controle com dieta padrão, animais apoE-/- com dieta aterogênica e animais apoE-/- com dieta aterogênica tratados com NDBP crônicamente. O sangue dos animais foi coletado para dosagem de colesterol total. As aortas dos animais foram coletadas e processadas para estudos em banho de órgãos ou avaliação histológica da deposição de placa (coloração Oil-Red), produção de EROs (DHE) e NO (DAF-2DA). A função vascular foi avaliada por meio da construção de curvas concentração-resposta à ACh (100 pM – 30 μM), após pré-contração com fenilefrina (FEN, 10 μM) e curvas concentração-resposta à FEN (100 pM – 30 μM). Para avaliar a produção basal de NO por método indireto, após uma pré-contração com FEN (10μM) os anéis foram incubados com o inibidor não específico da isoformas da óxido nítrico sintase L-NAME (100 μM). Com intuito de avaliar a influência do NDBP sobre a função vascular, os anéis foram incubados com NDBP (10 μM) em seguida foram realizados os testes de função vascular. A avaliação da atividade vasorrelaxante do NDBP foi realizada por meio de curvas concentração-resposta ao NDBP (100 pM – 30 μM) após pré-contração com FEN (10 μM) em anéis com e sem endotélio. Para avaliar se o efeito do NPBP sobre a função vascular é dependente de NO ou de atividade antioxidante, os anéis foram incubados com NDBP (10μM) mais hidroxicobalamina (HDX, 100μM) ou tempol (1μM). No grupo apoE-/- que foi tratado cronicamente por 14 dias, após o tratamento foi realizado teste de função vascular e avaliação da produção basal de NO. Os animais apoE-/- apresentaram incremento de aproximadamente 12 vezes nos níveis de colesterol (CT 58.2±3.6 vs. apoE-/- 704.9±29.9) e marcante deposição de placa (CT 0±0 vs. apoE-/- 57±4.9). Nos grupos sem tratamento crônico observou-se que os animais apoE-/- demonstraram marcante disfunção endotelial com comprometimento no relaxamento a ACh (CT Rmáx: 76.7±5.4 e pD2: 7.9±0.3 vs. apoE-/- Rmáx: 62.7±5.5 e pD2: 6.7±0.2) e maior resposta a FEN (CT Rmáx: 51.1±9.2 e pD2: 6.8±0.06 vs. apoE-/ Rmáx: 82.0±8.3 e pD2: 6.8±0.07). Através de método indireto, a produção de NO endógeno encontrou-se diminuída nesses animais, demostrada pela diminuição no delta de contração após bloqueio com L-NAME (CT 0.46±0.04 e 45.3±4.1% vs. apoE 0.30±0.01 e 33.2±1.9%). O mesmo foi observado através do método direto utilizando DAF-2DA: os animais apoE-/- apresentaram diminuição na produção de NO (CT 131855±15774 vs. apoE-/- 84057±13397). A produção de NO diminuída nos animais apoE-/- foi revertida após incubação com NDBP, demonstrada por aumento na concentração de NO medida por DAF-2DA em ambos os grupos (CT 196357±18312 vs. apoE-/- 223507±6996). Através da utilização da sonda DHE observou-se que os animais apoE-/- apresentaram aumento na produção de EROs (CT 114036±15280 vs. apoE-/- 166649±13022) e após incubação com NDBP a produção de EROs foi diminuída nesses animais (136043±8281). O NDBP promoveu relaxamento vascular na mesma proporção em ambos os grupos na ausência de endotélio (apoE-/- Rmáx: 93±4.1 e pD2: 5.8±0.3; CT Rmáx: 102±9.6 e pD2: 5.6±0.4), porém na presença de endotélio os animais apoE-/- demonstraram maior sensibilidade ao composto (Rmáx: 76±11,3 e pD2: 7,2±0,4) quando comparados ao controle (Rmáx: 69±6,7; pD2: 7,3±0,4). Após incubação com NDBP o prejuízo ao relaxamento a ACh observado nos animais apoE-/- foi revertido (79,4±3,9; pD2: 8,2±0,4) quando comparado ao controle (Rmáx: 76,0±3.7; pD2: 7,9±0,2). A melhora da função vascular induzida pelo NDBP foi abolida após incubação conjunta com HDX (Rmáx: 59,9±7,1 e pD2: 6,6±0,3). O relaxamento induzido pelo NDBP em vasos de animais apoE-/- sem endotélio (Rmáx: 93±4,1; pD2:5,8±0,3) foi abolido após pré-incubação com HDX (Rmáx: 0,5±0,6; pD2: 6,8±0,9). No intuito de avaliar se o NDBP possui atividade antioxidante, o tempol (mimético da SOD) foi pré-incubado com ou sem NDBP. O tempol pré-incubado com NDBP não tem seu efeito potencializado (Rmáx: 65,1±7,3) quando comparado ao tempol sem NDBP (Rmáx: 67,4±9,5). Os animais apoE-/- tratados cronicamente com NDBP (40mg/kg/in), apresentaram reversão no quadro de disfunção endotelial, demonstrado por melhora na resposta de relaxamento a ACh quando comparado aos animais apoE-/- não tratados (Rmáx: 87,4±3,1; pD2: 7,8±0,1 vs. Rmáx: 62,7±5,5; pD2: 6,7±0,2 respectivamente), equiparando aos animais controle (Rmáx:76,7±5,4; pD2: 7,9±0,3). Também apresentaram aumento na produção basal de NO demonstrado pelo aumento no delta de contração quando comparado ao apoE-/- não tratado (Δ: 0,39±0,2 vs. Δ: 0,30±0,01 respectivamente). Desta maneira, é possível concluir que o NDBP apresenta efeitos benéficos na aterosclerose experimental, sendo capaz de reverter o quadro de disfunção endotelial através do aumento da biodisponibilidade de NO e de seu efeito antioxidante.
  • ELLEN SONNALY VILAR RAMALHO
  • Avaliação da variabilidade da frequência cardíaca em sedentários submetidos ao treinamento resistido e aeróbico
  • Fecha: 30-ago-2019
  • Hora: 10:00
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  • A prática regular do exercício físico resistido (ER) vem sendo utilizada como estratégia de redução ao risco de doenças cardiovasculares, sendo recomendada tanto para indivíduos saudáveis quanto para pacientes portadores de doenças cardiovasculares. Os ER associados à alteração da composição corporal melhoram a condição física e diminuem a incidência de sobrepeso, promovendo uma série de respostas fisiológicas resultantes de adaptações autonômicas e hemodinâmicas que influenciam na função do sistema cardiovascular. A variabilidade da frequência cardíaca (VFC), utilizando o método do domínio da frequência, é uma ferramenta útil para avaliar o balanço autonômico cardíaco. Neste estudo longitudinal, em homens (n = 47) e mulheres (n = 51) normotensos, sedentários expostos ao exercício aeróbico (EA), foram investigados os parâmetros antropométricos [peso, índice de massa corporal (IMC) e percentual de gordura, glicemia, pressão arterial e frequência cardíaca. Ao final dos treinamentos, foram realizados os testes ortostático (TO) e a manobra de Valsalva (MA) para avaliação da VFC, utlizando o software nerve express. Os resultados mostraram que os ER e EA promovem redução dos parâmetros antropométricos no grupo feminino, bem como redução do percentual de gordura em ambos os gêneros. Os ER e EA promoveram bradicardia de repouso e redução da PAM basal em ambos os gêneros. Interessantemente, a redução da PAM após ER foi maior no grupo feminino em relação ao masculino. Na avaliação do sistema nervoso autônomo pela VFC os resultados mostraram que o ER promoveu um aumento significativo no HF do grupo feminino, sem alterações no grupo EA. Na comparação entre os exercícios no grupo feminino, os resultados mostraram que o ER promoveu um aumento significatvo no HF em relação ao EA. Quanto a análise espectral da VFC na MV combinado com respiração profunda, os ER e EA não promoveram alterações significativas nos componentes HF, LF ou da relação LF/HF (ms2). Nossos resultados sugerem que o ER, além das alterações antropométricas, promove importantes alterações autonômicas que influenciam o funcionamento cardiovascular e o metabólico. Os resultados sugerem que o ER pode ser indicado para estilo de vida saudável, bem como para a prevenção de doenças cardiometabólicas, sobretudo em indivíduos com históricos familiares.
  • RAYANNE MAIRA FELIX RIBEIRO ALVES
  • Efeito do Carvacrol em Ratos com Hipertensão Pulmonar Induzida por Monocrotalina
  • Fecha: 26-ago-2019
  • Hora: 14:00
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  • acarreta na elevação da pressão arterial pulmonar (PAP), insuficiência ventricular direita e morte. O carvacrol (CRV) é um monoterpeno fenólico presente em algumas plantas aromáticas e apresenta propriedades importantes como a atividade vasorelaxante, anti-inflamatória, antibacteriana e antitumoral. Diante disto, o objetivo do trabalho foi avaliar os efeitos do carvacrol no tratamento de ratos com HP induzida pela monocrotalina. Para o desenvolvimento deste estudo, ratos Wistar receberam injeção subcutânea com salina 0,9% (grupo controle - CTL) ou monocrotalina (60 mg/Kg) para indução da HP. Os animais foram divididos nos seguintes grupos: CTL; MCT; MCT+CRV 50mg/Kg; MCT+CRV 100mg/Kg; e MCT+SILD (sildenafila 50mg/Kg). Após 24 horas, os ratos foram tratados diariamente por administração oral durante 28 dias. Os seguintes parâmetros foram avaliados: pressão arterial pulmonar (PAP), razão entre o peso do ventrículo direito sobre o peso do ventrículo esquerdo e septo (índice de Fulton), reatividade vascular, remodelamento vascular pulmonar e produção de ânions superóxido. A aferição da PAP mostrou que o grupo MCT (37 ± 3 mmHg; n= 4) apresentou aumento na pressão sistólica ventricular direita quando comparado ao grupo CTL (20 ± 2 mmHg; n= 4). Os grupos MCT+CRV 50mg/Kg (24 ± 1 mmHg; n= 4) e MCT+SILD (21 ± 4 mmHg; n= 4) atenuaram significativamente a pressão. Quanto ao índice da hipertrofia ventricular direita o grupo MCT (0,38± 0,02 g; n= 4) mostrou um aumento quando comparado ao grupo CTL (0,23 ± 0,04 g; n= 4). Os grupos MCT+CRV 50mg/Kg (0,26 ± 0,02g; n= 4) e MCT+CRV 100mg/Kg (0,26 ± 0,05g; n= 4) reduziram significativamente a hipertrofia ventricular direita. A análise de reatividade vascular mostrou que as contrações frente fenilefrina (FEN), assim como, vasodilatação frente acetilcolina (ACh) ou nitroprussiato de sódio (NPS) foram significativamente reduzidas (Emáx = 66 ± 5%; n= 6, Emáx = 44 ± 8%; n= 6, ou Emáx = 78 ± 3%; n= 8, respectivamente) no grupo MCT quando comparado ao grupo CTL. Por outro lado, o tratamento com CRV (MCT+CRV 50 mg/kg ou MCT+CRV 100 mg/kg) melhoraram significativamente as contrações frente FEN (Emáx = 98 ± 9%; n= 6, ou Emáx= 88 ± 8%; n= 6, respectivamente) ou vasodilatação frente ACh (Emáx= 75 ± 8%; n= 7, ou Emáx = 130 ± 13%; n= 5, respectivamente). Contudo, alterações significativas não foram observadas ao NPS, com exceção do grupo MCT+CRV 50mg/kg (Emáx = 90 ± 2%; n= 8), que demonstrou melhora a vasodilatação frente NPS. As análises histológicas da parede da artéria pulmonar demonstraram que o grupo MCT (310 ± 5,2 %; n= 5) apresentou espessamento da parede do vaso, com aumento significativo de células musculares lisas quando comparados ao grupo CTL (100 ± 5,2 %; n= 5). Os grupos MCT+CRV 100mg/Kg (147 ± 10,5 %; n= 5) e MCT+SILD (94 ± 10,5 %; n= 5) atenuaram a proliferação de células musculares lisas. Quanto à análise de estresse oxidativo nos tecidos das artérias pulmonares, foi observado que o grupo MCT (216 ± 22%; n= 5) apresentou elevada porcentagem de fluorescência, quando comparados ao grupo CTL (100 ± 6%; n= 5). Os grupos MCT+CRV 50mg/Kg (119 ± 8%; n= 5); MCT+CRV 100mg/Kg (68 ± 6%; n= 5) e MCT+SILD (96 ± 7%; n= 5) atenuaram este estresse oxidativo. Estes resultados demonstram que o modelo escolhido para indução da HP, a monocrotalina, é eficaz ao levar as alterações estruturais e funcionais da artéria pulmonar, gerando alterações fisiológicas semelhantes ao que ocorre em humanos, ademais, o carvacrol mostrou ser uma substância promissora para o tratamento da HP visto que, atenua a pressão arterial pulmonar, hipertrofia ventricular direita, remodelamento vascular pulmonar, melhora a disfunção endotelial, e reduz o estresse oxidativo.
2018
Descripción
  • DEYSE CRISTINA MADRUGA CARVALHO
  • Atividade anti-inflamatória da marinobufagina em modelos in vivo e in vitro
  • Fecha: 30-abr-2018
  • Hora: 10:00
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  • Os esteroides cardiotonicos sao compostos naturais capazes de inibir a Na+/K+-ATPase. Esses esteroides, tais como, a marinobufagina e a ouabaina, foram identificados como substancias endogenas presentes no plasma de mamiferos. Nosso grupo vem evidenciando o papel modulador da ouabaina na resposta imunologica, pela descricao e caracterizacao de seu efeito anti-inflamatorio. No entanto, ainda nao ha relatos na literatura sobre a marinobufagina nesse aspecto. Dessa forma, o objetivo deste trabalho foi analisar, in vivo e in vitro, o papel da marinobufagina na inflamacao. Inicialmente, camundongos Swiss foram tratados via intraperitoneal (i.p.) com a marinobufagina na dose 0,56 mg/kg, a mesma utilizada nos experimentos com a ouabaina (LEITE et al., 2015), durante tres dias consecutivos. Uma hora apos o ultimo dia de tratamento, os animais foram estimulados com zimosan (2 mg/mL) via intraperitoneal, de modo a induzir uma inflamacao no peritonio. Apos 4 h, o fluido peritoneal foi coletado e utilizado para a contagem das celulas por microscopia optica e para a quantificacao das citocinas pro-inflamatorias (IL-1β, IL-6 e TNF-α) pelo ensaio imunoenzimatico (ELISA). O zimosan, como esperado, induziu aumento da migracao celular e dos niveis das citocinas pro-inflamatorias no peritonio. Por sua vez, o tratamento com a marinobufagina foi capaz de reduzir o numero total de celulas para a cavidade peritoneal, pela reducao na migracao das celulas polimorfonucleares. Alem disso, esse esteroide foi capaz de reduzir os niveis das citocinas IL-1β e IL-6. Esse efeito parece ser independente do TNF-α, visto que os seus niveis nao foram alterados. Adicionalmente, foi avaliado o efeito da marinobufagina in vitro, pela cultura de macrofagos peritoneais com o estimulo do zimosan (2 mg/mL) ou lipopolissacarideo (LPS) (1 μg/mL). Na cultura de macrofagos com o estimulo do zimosan, observou-se que as diferentes concentracoes da marinobufagina (10, 100, 1.000 e 10.000 nM) nao interferiram na viabilidade dos macrofagos peritoneais e apenas a menor concentracao foi capaz de reduzir os niveis das citocinas pro-inflamatorias IL-1 β, IL-6 e TNF-α. Na cultura de macrofagos com o estimulo do LPS, foi observado que todas as concentracoes da marinobufagina foram capazes de reduzir a producao do oxido nitrico (NO) nessas celulas. Dessa forma, a partir da analise dos resultados, pode-se sugerir que ha evidencias de que a marinobufagina possui papel anti-inflamatorio in vivo e in vitro. Portanto, esse trabalho e pioneiro em caracterizar o papel imunologico do esteroide cardiotonico marinobufagina.
  • REPHANY FONSECA PEIXOTO
  • Investigação da Imunomodulação por Subpopulações de Linfócitos na Leishmaniose Visceral Humana
  • Fecha: 25-abr-2018
  • Hora: 14:00
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  • As leishmanioses se caracterizam como um complexo de doencas infecto-parasitarias, causadas por protozoarios do genero Leishmania. Essas doencas estao presentes em 98 paises, nos quais cerca de 350 milhoes de pessoas encontram-se sob risco de infeccao. A leishmaniose visceral (LV) e a forma clinica mais grave da doenca e induz respostas imunes mediadas por distintas subpopulacoes celulares, incluindo celulas T natural killer invariantes (iNKT-CD3+6B11+), celulas T reguladoras (Tregs - CD4 + CD25 high FOXP3 +), as quais podem ser classificadas em Treg natural (CD4 + CD25 high FOXP3 + CD45RA +) e Treg de memoria (CD4 + CD25 high FOXP3 + CD45RA-). Entretanto, os mecanismos de acao dessas subpopulacoes, envolvidos na modulacao imunologica da leishmaniose visceral humana, ainda nao foram bem elucidados. Assim, nosso objetivo foi caracterizar os mecanismos das celulas iNKT, celulas T reguladoras natural (nTreg) e de memoria (mTreg) na doenca e avaliar as principais citocinas produzidas por elas. Para atingir esse objetivo, na primeira parte desse trabalho coletou-se sangue total de pacientes LV (n=11) e individuos nao infectados (n=7), e as subpopulacoes nTreg e mTreg foram avaliadas, com e sem estimulacao especifica do antigeno soluvel de Leishmania (SLA). A analise das celulas iNKT tambem foram realizadas, com e sem estimulacao especifica do antigeno total de Leishmania (TLA) em amostras de sangue total nos grupos de pacientes LV (n=12), em controles nao endemico (CNE – n = 6) e no grupo controle negativo endemico (CNegE – n = 6). Todas as analises foram realizadas atraves de citometria de fluxo. Em relacao as celulas Tregs, os resultados demonstraram que: 1) Um numero elevado de celulas Tregs de memoria foi observado quando comparado ao numero total de celulas Tregs naturais em todos os grupos avaliados; 2) Uma reducao significativa na expressao de CD39/CD73 em celulas Treg de memoria foi observada nos grupos LV independentemente de estimulo; 3) Uma diminuicao na expressao de CTLA-4 foi observada em celulas Treg de memoria no grupo LV na ausencia de estimulo, quando comparada ao grupo controle. Entretanto, o SLA induziu aumento de expressao de CTLA-4, nos pacientes com LV; 4) Alteracoes significativas na producao de IFN-γ nao foram observadas em nenhum dos grupos avaliados e 5) Baixos niveis de IL-10 foram observados em celulas Treg de memoria nos grupos LV independentemente de estimulo. Ja nas celulas iNKT observamos que, 6) o numero total ex vivo de celulas no grupo de pacientes LV nao se alterou significativamente em relacao aos grupos CNE e CNegE; 7) Em relacao ao perfil de ativacao recente dessas celulas, os pacientes LV nao apresentaram alteracoes significativas na expressao de CD69, em comparacao aos grupos controle tanto ex vivo como apos a cultura in vitro (meio e TLA); 8) Apos o estimulo com TLA de L. infantum as celulas iNKT reduziram a producao de IFN-γ. No entanto, a maior producao de IFN-γ foi observada em celulas iNKT no grupo CNE; 9) Em relacao a producao de IL-17, alteracoes significativas nao foram observadas, antes ou apos a estimulacao com o TLA, em todos os grupos avaliados; 10) Uma elevacao na producao de IL-10, foi observada no grupo CNE quando comparado ao CNegE e pacientes com LV de forma independente a estimulacao. Dessa forma, sugere-se que apesar da manutencao da regulacao por celulas nTreg, o perfil pro-inflamatorio esta favorecido pela reducao de mecanismos regulatorios de celulas mTreg e modulacao positiva de mecanismos de celulas iNKT.
  • ARACELE TOSCANO ROCHA
  • Disfunção autonômica cardíaca em crianças e adolescentes obesos após manobra de valsalva
  • Fecha: 05-mar-2018
  • Hora: 09:00
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  • A obesidade infantil e um grande problema de saude publica. A associacao entre obesidade e disfuncao autonomica cardiaca, entre adultos, ja e consensual, e na faixa etaria pediatrica ainda e motivo de varias investigacoes. Nosso estudo objetivou avaliar a modulacao autonomica cardiaca em criancas e adolescentes obesos, na faixa etaria de 6 a 14 anos de idade, de ambos os sexos, sem outras comorbidades associadas, por meio do estudo da variabilidade da frequencia cardiaca e determinar os niveis de insulina e perfil lipidico nesse grupo. Foram estudadas 59 criancas, sendo 44 (74,6%) classificadas como pre-puberes e 15 (25,4%) classificadas como puberes. As criancas foram agrupadas de acordo o indice de massa corporal (IMC), onde 23 (39%) criancas foram classificadas como eutroficas, 16 (27,1%) criancas classificadas como obesas e 20 (33,9%) com obesidade grave. Todas foram submetidas a avaliacao antropometrica, clinica e laboratorial, bem como a analise da variabilidade da frequencia cardiaca (VFC) por meio do software Nerve Express®, estudando-se as variaveis no dominio do tempo (SDNN) e no dominio da frequencia (TP, LF, HF, LF/HF), dividido em 2 etapas, o teste ortostatico, seguido da manobra de Valsalva combinada com respiracao profunda. Foi realizada uma analise estatistica descritiva dos dados. Para os testes de hipotese foram utilizados o ANOVA e o teste de correlacao de Pearson, sendo o nivel de significancia adotado de p<0,05. Na avaliacao laboratorial, obteve-se valores elevados de insulina no grupo de pacientes obesos graves quando comparados ao eutrofico (p= 0,019). Os niveis de triglicerideos foram maiores nas criancas obesas e obesas graves em relacao as eutroficas (p= 0,001). Os valores de colesterol total foram semelhantes entre os grupos, porem a fracao HDL foi significantemente menor nos obesos (p= 0,009). Durante a realizacao do teste ortostatico, nao houve diferencas nos indices de VFC entre os grupos eutrofico e obeso/obeso grave, tanto na posicao supino, como na bipede. Na analise da VFC durante a realizacao da manobra de Valsalva combinada com a respiracao profunda, encontramos uma reducao da atividade parassimpatica, representada pela diminuicao do componente HFun no grupo de obesos, principalmente no de obesos graves (p=0,010), e um aumento de atividade simpatica, observado atraves de valores maiores de LFun (p= 0,010) e da razao LF/HF (p= 0,001) no grupo obesos/obesos graves quando comparados aos eutroficos. Apos estes resultados, pode-se sugerir um comprometimento da funcao autonomica cardiaca em criancas e adolescentes obesos, principalmente nos obesos graves, bem como niveis de insulina e triglicerideos mais significativos no grupo de obesos. Estes achados constituem fatores de risco que, de forma independente, podem contribuir para o aumento do risco cardiovascular neste grupo.
2017
Descripción
  • CRISTIANE RODRIGUES DE ALMEIDA SILVA ALVES
  • Agonista tendencioso para o receptor AT1 exerce efeitos benéficos sobre parâmetros cardiovasculares de ratos espontaneamente hipertensos.
  • Fecha: 01-nov-2017
  • Hora: 09:00
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  • A hipertensao arterial (HA) e uma desordem que resulta do prejuizo nos mecanismos de controle da pressao arterial, dentre os quais destacam-se o barorreflexo e o Sistema Renina Angiotensina Aldosterona (SRAA). As acoes da Angiotensina II no receptor do tipo AT1 (AT1R) sao determinantes para a elevacao da pressao arterial via ativacao da fosfolipase C (PLC). Devido a esse fato, antagonistas do AT1R tem sido boas opcoes para o tratamento da HA, porem com efeitos colaterais indesejados. O TRV027 e um agonista tendencioso para o receptor AT1, ou seja, e capaz de se ligar ao AT1R sem ativar a PLC, mas sim algumas MAPKs e a β-arrestina, promovendo como resultado a ativacao de vias cardioprotetoras. Estudos apontam o TRV027 como uma droga em potencial para o tratamento da insuficiencia cardiaca, porem nada tem sido relatado sobre esse composto na hipertensao. O objetivo do presente trabalho foi investigar os efeitos do TRV027 sobre a pressao arterial, a sensibilidade do barorreflexo e o estresse oxidativo plasmatico e tecidual em ratos normotensos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Os ratos WKY e SHR foram divididos em quatro grupos: WKY Controle (WKY-C), WKY tratado com o TRV027 (WKY-T), SHR Controle (SHR-C) e SHR tratado com o TRV027 (SHR-T). O tratamento com o TRV027 foi realizado por via intracerebroventricular utilizando minibombas osmoticas acopladas a uma canula guia implantadas em direcao ao ventriculo lateral dos animais, por meio das quais o composto foi injetado durante 14 dias (20 ng/kg/dia). No 13º dia do tratamento, foram implantados cateteres na veia e arteria femorais dos animais para administracao de drogas e avaliacao dos parametros cardiovasculares, respectivamente. Em seguida, os animais foram sacrificados e foi feita a coleta de sangue, rins e figado para avaliacao do estresse oxidativo pelo metodo do acido tiobarbiturico. Todos os protocolos foram aprovados pelo CEUA-UFPB (parecer nº 109/2015). O tratamento com TRV027 nao apresentou efeitos significativos na pressao arterial dos animais normotensos (WKY-C: 119 ± 3 vs. WKY+TRV: 108± 3 mmHg), mas foi eficiente em reduzir a pressao arterial nos animais SHR+TRV quando comparados ao grupo SHR-C (160 ± 3 vs.181 ± 3 mmHg, respectivamente, p<0,05), nao foi observada diferenca significativa na frequencia cardiaca entre os grupos avaliados. O tratamento melhorou o tonus vagal tanto nos animais WKY (ΔFC = 72 ± 4 vs. 110 ± 5 bpm, p<0,05) quanto nos animais SHR (ΔFC = 54 ± 4 vs. 83 ± 1 bpm, p< 0,05), assim como reduziu o barorreflexo espontaneo nestes ultimos (SHR-C: 0,5 ± 0,1 vs. SHR+TRV: 1,8 ± 0,3, p<0,05). O TRV027 tambem foi capaz de reduzir os niveis plasmaticos e renais de MDA nos animais SHR+TRV quando comparados ao grupo SHR-C (Soro: 0,37 ± 0,05 vs. 2,58 ± 0,08nmol/ml; Rins: 8,18 ± 0,03 vs. 11,7 ± 0,05 nmol/mg do orgao). Os resultados obtidos demonstram que o TRV027, atuando no Sistema Nervoso Central, e capaz de reduzir a PA de ratos espontaneamente hipertensos, melhorar a atividade vagal, restaurar a sensibilidade do barorreflexo e reduzir o estresse oxidativo presente nesses animais. Esses dados reforcam o envolvimento do AT1R no processo hipertensivo bem como apontam para o potencial benefico do agonista tendencioso TRV027 contra a hipertensao e eventos a ela relacionados.
  • ESTEVAM LUIZ DE SOUZA JUNIOR
  • Avaliação da variabilidade cardíaca durante acompanhamento de indivíduos que fazem uso de esteróides anabólicos de maneira recreativa
  • Fecha: 24-ago-2017
  • Hora: 09:00
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  • O uso indiscriminado de esteroides anabolicos de maneira recreativa por praticantes de atividades fisicas pode constituir-se de um grave problema para a saude. No presente trabalho investigamos as possiveis alteracoes hormonais, bioquimicas e na variabilidade da frequencia cardiaca de pacientes que se apresentaram na clinica para acompanhamento alegando estarem se submetendo a diferentes protocolos de uso de esteroides. Com base na cauistica, os pacientes foram divididos em 4 grupos: grupo I: pacientes que usaram apenas testosterona; grupo II: pacientes usando testosterona e deca durabolim; grupo 3 pacientes utilizando testosterona + deca durabolim + oxandrolona e grupo IV: pacientes que nao usavam esteroides, os quais serviram como controle. Nao forma observadas alteracoes na variabilidade da frequencia cardiaca dos pacientes ao longo das 6 semanas de acompanhamento. Os valores de HDL se mostraram reduzidos nos grupos que usaram esteroides, independente da combinacao. Os marcadores de funcao hepatica TGO e TGP se apresentaram aumentados no grupo III, o qual os pacientes estavam sob a influencia de 3 drogas anabolicas. Observou-se tambem um bloqueio do eixo hipotalamo-hipofise destes pacientes nos 3 grupos sob uso de esteroides, evidenciado pela reducao significativa dos niveis de LH e FSH, provavelmente causando comprometimento gonadal nestes pacientes. Nossos achados sugerem que o uso recreativo de esteroides anabolicos induz ao bloqueio do eixo hipotalamo hiposide, causando comprometimento gonadal e que a combinacao de tres esteroides pode ocasionar comprometimento hepatico. Entretanto, nao forma observadas alteracoes na variabilidade da frequencia cardiaca destes pacientes.
  • TAÍSA FRANÇA DE MEDEIROS ASSIS
  • Avaliação do estresse oxidativo no órgão subfornical e no bulbo ventrolateral rostral de animais knockout para apolipoproteína E
  • Fecha: 13-jun-2017
  • Hora: 09:00
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  • A aterosclerose e uma doenca multifatorial, considerada como um dos principais fatores de risco que levam ao desenvolvimento de doenca cardiovascular. E caracterizada por disfuncao endotelial e autonomica devido a presenca de inflamacao e estresse oxidativo sistemico. O objetivo deste trabalho foi avaliar a presenca de EROs no orgao subfornical (SFO) e no bulbo ventrolateral rostral (RVLM) de animais knockout para apolipoproteina E (apoE-/-), alimentados com dieta padrao e a possivel relacao da presenca de citocinas inflamatorias perifericas com a geracao de estresse oxidativo central. Para isso foi realizada a coleta do soro de camundongos C57BL/6, camundongos isogenicos, e apoE-/-, camundongos, tambem isogenicos, geneticamente modificados para a delecao do gene que codifica a apolipoproteina E. O soro foi utilizado para a dosagem do colesterol, da peroxidacao lipidica na forma de malonialdeido (MDA) e das citocinas inflamatorias (IL-1β, TNF-α e IL-10). Alem disso, foram coletadas as aortas de ambos os grupos para a avaliacao “en face” da deposicao lipidica. Ainda foi realizada a coleta de amostras do SFO e do RVLM dos dois grupos para a realizacao da dosagem de especies reativas de oxigenio pela tecnica do di-hidroetidio (DHE) e para a quantificacao de citocinas inflamatorias (IL-1β, TNF-α e IL-10) no SFO. Observamos um aumento significativo dos niveis de colesterol total nos animais apoE-/- em relacao aos animais controle (237,4±17,7 mg/dL n=6 vs 90,7±6,4 mg/dL n=6, p<0,05), ambos alimentados com dieta padrao e com idade de 13 meses. Observamos tambem uma maior deposicao lipidica nos animais apoE-/- quando comparados com os controles (27,7±4,8% n=3 vs 5,3± 0,6% n=4, p<0,05, respectivamente). Houve aumento nos niveis sericos de malondialdeido nos camundongos apoE-/- quando comparados com o controle (1,8±0,2 nmol/mL, n=15 vs 1,1±0,2 nmol/mL, n=12, p<0,05). Com relacao a avaliacao inflamatoria sistemica, observamos aumento nos niveis de IL-1β nos animais apoE-/- quando comparados aos controles (17,7±2,9 pg/mL, n=11 vs 5,8±0,5 pg/mL, n=11, p<0,05), bem como o TNF-α que tambem se apresentou elevado nos animais ateroscleroticos (4,6±0,8 pg/mL, n=8 vs 2,1±0,6 pg/mL, n=8, p<0,05). No entanto, nao constatamos diferenca significativa nos niveis de IL-10 quando comparamos ambos os grupos (apoE-/-:201,6±16,0 pg/mL,n=6 vs C57BL/6:190,1±11,1 pg/mL,n=6). Quanto a avaliacao do estresse oxidativo no SFO e no RVLM foi observado aumento nos niveis de O2•- em ambas as areas dos camundongos apoE-/- quando comparados com o controle (SFO: 36,4±2,1 FR/u.a, n=4 vs 19,4±2,1 FR/u.a, n=4, p<0,05; RVLM: 31,7±2,7 FR/u.a, n=4 vs 16,0±1,0 FR/u.a, n=5, p<0,05). Por fim avaliamos os niveis de citocinas inflamatorias no SFO e observamos uma diminuicao nos niveis tanto das citocinas pro-inflamatorias (TNF-α como da IL-1β), como da IL-10 (anti-inflamatoria) nos camundongos apoE-/- quando comparados com o controle: IL-1β (4,4±0,3 pg/mL n=5, vs 9,1±0,8 pg/mL n=5, p<0,05), TNF-α (3,0±0,7pg/mL, n=7 vs 6,4±0,9 pg/mL n=7, p<0,05), IL-10 (214,0±1,9 pg/mL n=3, vs 354,2±19,3 pg/mL n=3, p<0,05). Portanto, concluimos que os animas apoE-/- alimentados com dieta padrao apresentam niveis elevados de EROs no SFO e RVLM, que em conjunto, sao importantes regioes responsaveis pelo controle cardiovascular. Podemos ainda sugerir que as citocinas inflamatorias perifericas participam da inducao do estresse oxidativo central a partir da sua acao no SFO.
  • MÁRCIA DANTAS DOS SANTOS
  • Influência do fotoperíodo sobre o relógio molecular e o eixo somatotrópico de alevinos da tilápia-do-Nilo (Oreochromis niloticus)
  • Fecha: 31-may-2017
  • Hora: 09:00
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  • A maioria dos organismos vivos possui um ciclo habitual do qual desenvolve todas suas atividades. Estas sao geradas internamente pelo relogio molecular e sincronizadas pelos fatores abioticos a um periodo em torno de 24 horas. Para os peixes, o fotoperiodo e um dos sincronizadores ambientais que apresenta uma grande influencia sobre o relogio molecular, coordenando fatores ambientais com sua a fisiologia. Um dos sistemas que parece estar sob a influencia do relogio molecular endogeno e o sistema endocrino, precisamente, o eixo somatotropico. Para investigar a relacao entre o relogio e o sistema endocrino, objetivamos analisar a expressao de um gene do relogio molecular, o clock1a, e o gene do eixo somatotropico, gh, de alevinos de tilapia-do-Nilo (Oreochromis niloticus) quando expostos aos fotoperiodos de 12h:12h e 24h:0h claro:escuro (7 animais a cada 6h; e verificar a influencia do fotoperiodo sobre o comprimento, massa, crescimento corporal e fator de condicao. Os alevinos foram mantidos no fotoperiodo por 7 dias e a biometria foi realizada nos XX dias. Ao final da exposicao, os animais foram sacrificados e o cerebro foi extraido para quantificacao da expressao genica. Em relacao ao comprimento nao observamos diferencas em funcao do fotoperiodo, exceto, nos tempos 22 e 37 (dia), cujas medias foram de 4,95±0,36, 4,75±0,41 e 6,65±0,66, 6,39±0,68 para o claro:claro (C:C) e claro:escuro (C:E), respectivamente. No tocante a massa corporal, teve-se diferenca, apenas, no tempo de 7 dias, com 1,08±0,23 C:C e 0,98±0,23 C:E, respectivamente. No que se refere ao crescimento, nao foram observadas diferencas significativas entre os tratamentos, exceto entre o dia 7 e 37 que apresentaram um crescimento diferenciado em que condicao de fotoperiodo. Com relacao ao fator de condicao, os dados nao revelaram diferencas significativas entre os tratamentos. Os genes analisados nao apresentaram padrao circadiano de expressao, mas o gene clock1a, apresentou grandes diferencas nos seus niveis diarios, isto e, entre os pontos de amostragem para as duas condicoes de fotoperiodo. Tambem foram observadas oscilacoes de expressao maiores para o fotoperiodo C:E para o gene clock1a. O gh, por sua vez, nao apresentou um ritmo biologico como tambem ausencia de diferencas entre os tempos nas condicoes. Por fim, foi testada a possibilidade de uma correlacao entre os genes supracitados nas suas respectivas condicoes de fotoperiodo. Contudo, os escores resultantes foram altamente distantes de qualquer correlacao. Em sintese, a exposicao aos fotoperiodos nao interferiram de maneira significativa no comprimento, crescimento, massa corporal e fator condicao de alevinos de tilapia-do-Nilo. Porem, observou-se que os peixes podem sofrer influencia do fotoperiodo num estagio de vida especifico.
2016
Descripción
  • RENATA DA SILVEIRA RODRIGUES PAIVA
  • CARACTERIZAÇÃO DO PERFIL DE MONÓCITOS: COMPARAÇÃO DA FENOTIPAGEM ENTRE ADULTOS E CRIANÇAS SADIAS E EM CRIANÇAS PORTADORAS DE DERMATITE ATÓPICA
  • Fecha: 15-dic-2016
  • Hora: 09:00
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  • Os monocitos/macrofagos representam componente fundamental da resposta imune. Com base na expressao do co-receptor de LPS CD14 e na expressao do CD16, receptor FCγIII, os monocitos/macrofagos sao classificados em 3 subtipos: M1, ou monocitos classicos, que sao CD14+CD16-; Mi, ou monocitos intermediarios, que sao CD14hiD16+; e monocitos M2, nao-classicos, ou CD14lowCD16+. Nosso grupo realizou analise comparativa entre os subtipos monocitarios atraves do estudo da frequencia e da media de intensidade de fluorescencia (MFI) de moleculas de superficie (HLA-DR, CCR5, CD80, CD86, PD1L) e producao de citocinas (IL6, TNFα, IL10) em adultos e criancas utilizando a citometria de fluxo. A pesquisa foi executada em duas etapas. Primeiro comparamos os subtipos de monocitos entre adultos e criancas saudaveis e em seguida, entre criancas sadias e criancas portadoras de dermatite atopica (DA). A DA e uma doenca inflamatoria cutanea cronica, de etiologia multifatorial. O papel dos monocitos/macrofagos na ativacao, manutencao e modulacao do processo inflamatorio foi objeto da nossa investigacao. Os resultados desse estudo mostraram que: (1) a frequencia relativa dos subtipos de monocitos foi similar em adultos, criancas saudaveis e criancas portadoras de DA, com predominio de monocitos classicos; (2) monocitos M1, Mi e M2 de criancas atopicas apresentaram maior MFI de HLA-DR que os mesmos subtipos em criancas sadias e essas demonstraram maior MFI que adultos sadios; (3) adultos, criancas saudaveis e criancas doentes apresentaram maior expressao e MFI de CCR5 em Mi e M2 que em M1; (4) a expressao e MFI do CD80 foi maior em monocitos Mi e M2 tanto em criancas como em adultos saudaveis e a MFI de CD86 foi mais expressiva em Mi desses dois grupos. Ja a MFI das moleculas de CD80 e CD86 em M1 de criancas portadoras de DA foi maior que em criancas saudaveis; (5) a expressao de PD1L nos subtipos de monocitos foi semelhante em adultos e criancas, entretanto, houve maior MFI dessa molecula em M1 de criancas que em adultos saudaveis. Alem disso, criancas atopicas apresentaram maior MFI desta molecula em M1 que criancas saudaveis; (6) Mi e M2 de adultos e criancas saudaveis apresentaram maior atividade inflamatoria que M1 ao se avaliar a expressao e MFI de IL-6 e TNF-α, ao contrario do que se observou em criancas com DA, que apresentaram maior frequencia e MFI de IL-6 e TNF-α em M1 e Mi que as criancas saudaveis; (7) Mi e M2 demonstraram maior producao de IL10 que M1 em adultos e criancas saudaveis. Nossos resultados mostraram, portanto que a frequencia relativa de monocitos e constante nos tres grupos populacionais estudados, mas a frequencia e MFI de moleculas de superficie e citocinas apresentam particularidades significativas. Em resumo, criancas atopicas apresentam maior capacidade de apresentacao antigenica que criancas saudaveis e essas, que adultos saudaveis. Os subtipos de monocitos mais envolvidos na resposta inflamatoria em adultos e criancas sadias sao monocitos Mi e M2, enquanto monocitos M1 de criancas atopicas sao mais inflamatorios quando comparados ao mesmo subtipo em criancas saudaveis. Essas descobertas revelam alteracoes na resposta imunologica de criancas portadoras de dermatite atopica de extrema importancia para a compreensao da fisiopatologia da doenca.
  • ATALIA FERREIRA DE LIMA
  • Participação da glia hipotalâmica na modulação das respostas neuroendócrinas, comportamentais e cardio-respiratórias induzidas pela Angiotensina II no ventrículo lateral de ratos não anestesiados.
  • Fecha: 05-dic-2016
  • Hora: 08:20
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  • A Angiotensina II (ANGII) intracerebroventricular (icv) induz respostas neuroendocrinas, comportamentais e cardiovasculares. Sabendo que receptores AT1 e AT2 para ANG-II estao localizados em neuronios e celulas da glia dos orgaos circumventriculares, nossa hipotese e que as respostas neuroendocrinas, comportamentais e cardiorespiratorias induzidas pela ANG-II central sao mediadas, em parte, pela glia hipotalamica. O objetivo do presente estudo foi avaliar a participacao da glia hipotalamica na liberacao de Vasopressina (AVP) e Ocitocina (OT) plasmaticas, ingestao de agua e salina hipertonica (1,5%) e nas respostas cardiorespiratorias induzidas pela microinjecao de ANG-II no ventriculo lateral (VL) de ratos nao anestesiados. Utilizamos ratos Wistar [(260-280g) Ceua/Cbiotec nº133/2015]. Realizamos microinjecoes de Fluorocitrato [FCt (50 ou 100mM)], um inibidor da atividade da glia, de ANG II (0,05M ou 0,1M) ou de salina esteril (0,9%/500nl) no VL de ratos nao anestesiados. O plasma foi coletado para analise da concentracao AVP e OT plasmaticas, pela tecnica de radioimunoensaio. A analise da ingestao de agua e salina (1,5%) foi feita apos a adaptacao dos animais a gaiola metabolica. Em outro grupo de animais, a arteria femoral foi cateterizada para os registros da pressao arterial (PA, mmHg) e frequencia cardiaca (FC, bpm) basais. Para o registro da frequencia respiratoria (cpm) os animais foram colocados em uma camera pletismografica. Os resultados mostraram que a ANG II no VL promoveu um aumento na concentracao de AVP [2,3 ± 0,4 vs. 1,3 ± 0,1 pg / ml, p=0,039 (n=6)] e OT plasmaticas [3,7 ± 0,8 vs. 1,4 ± 0,2 pg / ml, p=0,025 (n=6)] comparada ao controle salina (0,9%). O FCt microinjetado no VL promoveu uma aumento na liberacao de OT plasmatica (2,6 ± 0,4 vs. 1,4 ± 0,2 pg / ml, p=0,024 (n=6)], mas nao alterou a concentracao plasmatica de AVP (0,99 ± 0,1 vs. 1,3 ± 0,1 pg/ ml, p=0,78 (n=6)]. A previa microinjecao de FCt atenuou a resposta a ANG II de aumento na concentracao de AVP (1,30 ± 0,16 vs 2,3 ± 0,4 pg / ml, p=0,05 (n=6)], mas nao de OT plasmatica (2,9 ± 0,4 vs. 3,9 ± 0,8 pg / ml, p=0,31 (n=5-6)]. A ANG II no VL promoveu aumento na ingestao cumulativa de agua (5,3 ± 1,6 vs. 1,2 ± 0,4 ml / 4 hrs, p=0,02 (n=4-6)] e de salina (1.5% NaCl) [16 ± 1 vs. 2,5 ± 0,7 ml / 4 hrs, p=0,0001 (n=5-6)]. O FCt nao promoveu alteracoes na ingestao cumulativa de agua [1,3 ± 0,3 vs. 1,2 ± 0,4 ml / 4 hrs,p=0,79 (n=5-6)], mas reduziu a ingestao cumulativa de salina (1.5% NaCl)[0,8 ± 0,3 vs. 2,5 ± 0,7ml / 4 hrs, p=0,04 (n=6)]. A previa microinjecao de FCt inibiu a resposta de apetite ao sodio [2,7 ± 0,3 vs. 16 ± 1 ml / 4 hrs, p=0,0001 (n=5-7)], mas nao alterou a ingestao de agua induzida pela ANG II no VL [8 ± 2,4 vs. 5,3 ± 1,6 ml / 4 hrs, p=0,44 (n=4-7)]. A ANG II no VL promoveu um aumento na PAM basal dos ratos [137,8 ± 4,9 vs. 115,1 ± 3,6 mmHg, p=0,002 (n=7)]. A resposta pressora promovida pela ANG II foi significativamente reduzida pela previa microinjecao do FCt no VL apos 5 minutos [Δ12,6 ± 2,1 vs. Δ22,6 ± 1,9 mmHg, p=0,004 (n=7)]. Nao foram observadas alteracoes promovidas pela ANG II [311,7 ± 37,9 vs. 352,4 ± 15 bpm, p=0,106 (n=7)] ou FCt [310,4 ± 16,7 vs. 341,3 ± 14 bpm, p=0,182 (n=7)] na FC basal (bpm) dos animais. A microinjecao de ANG II nao promoveu alteracao significativas na frequencia respiratoria basal {FR [109,6 ± 5,9 vs. 105,9 ± 4,6 cpm, p=0,63 (n=6)]}, no volume corrente {VT [8,6 ± 0,7 vs. 7,8 ± 0,7 mL.Kg-1, p=0,43 (n=6)]} ou no volume expirado no primeiro minuto {VE [950,7 ± 98,2 vs. 873,5 ± 86,7 mL.Kg-1.min-1, p=0,57 (n=6)]}. A microinjecao de FCt promoveu uma diminuicao significativa na frequencia respiratoria basal {FR [80,5 ± 3,8 vs. 102,2 ± 5,8 cpm, p=0,002 (n=6)]}, sem alteracoes significativas no VT [9,7 ± 0,6 vs. 7,8 ± 0,7 mL.Kg-1, p=0,66 (n=6)] e no VE basais [827,2 ± 57,3 vs. 873,5 ± 86,7 mL.Kg-1.min-1, p=0,66 (n=6)]. Nossos resultados sugerem que as celulas da glia hipotalamicas: a) participam da modulacao tonica da liberacao de OT plasmatica e da ingestao de sodio; b) modulam a resposta angiotensinergica central para a liberacao de vasopressina plasmatica, inducao da ingestao de sodio e de resposta pressora. c) alem disso, participam da modulacao da frequencia respiratoria basal em ratos nao anestesiados.
  • CLENIA DE OLIVEIRA CAVALCANTI
  • AVALIAÇÃO PRÉ-CLÍNICA DO EFEITO DO CITRATO DE SILDENAFIL SOBRE O CONTROLE CENTRAL DA PRESSÃO ARTERIAL NA HIPERTENSÃO
  • Fecha: 24-oct-2016
  • Hora: 09:00
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  • A hipertensao arterial sistemica (HAS) esta relacionada a diversos eventos cardiovasculares e desponta como uma das principais causas de obito atualmente. Na fisiopatologia da HAS ocorrem disfuncoes no sistema nervoso autonomo que resultam em prejuizo aos mecanismos neuronais de controle central da pressao, em especial ao barorreflexo. Parte deste dano e mediada pelo aumento do estresse oxidativo. Abordagens terapeuticas que reduzam o estresse oxidativo podem se mostrar eficazes no combate a esta doenca. O sildenafil e uma droga que atua inibindo a acao da fosfodiesterase 5 (PDE5) e tem sido observado que promove uma diminuicao do estresse oxidativo. A inibicao da PDE5 se mostrou eficiente na melhora da funcao vascular e reducao da pressao arterial em modelos experimentais. Contudo, seus efeitos sobre o controle barorreflexo da pressao arterial na vigencia de hipertensao resistente ainda nao foram estudados. O estudo atual teve como objetivo avaliar se o tratamento com sildenafil e capaz de influenciar o controle barorreflexo da pressao arterial. Foram utilizados ratos Wistar, submetidos a cirurgia sham ou indutora de hipertensao renovascular (2R1C). Apos 5 semanas, os animais receberam veiculo (agua) ou citrato de sildenafil (45mg/Kg/dia) durante 7 dias, perfazendo 4 grupos: sham + veiculo, sham + sildenafil, 2R1C + veiculo, 2R1C + sildenafil. Ao fim do tratamento os animais foram canulados para medidas hemodinamicas. Foram avaliados: pressao arterial media, frequencia cardiaca, barorreflexo espontaneo e induzido, tonus autonomico cardiaco e estresse oxidativo sistemico. (CEUA-UFPB protocolo n. 042/2015). O tratamento com sildenafil foi eficiente em reduzir a pressao arterial nos animais 2R1C (139 ± 5 vs.175 ± 6 mmHg, p < 0,01), sem efeitos significativos nos animais normotensos (121 ± 7 vs.118± 3 mmHg). Os animais 2R1C apresentaram reducao do ganho do barorreflexo induzido (-1,93±0,12) e espontaneo (-1,90±0,22), quando comparados aos sham (-3,63±0,31; -3,95 ± 0,46). Estes parametros foram normalizados nos animais hipertensos pelo tratamento com sildenafil (-3,18±0,23; -3,51 ± 0,29). Os bloqueios com atropina e propranolol revelaram alteracoes no balanco autonomico cardiaco na vigencia de hipertensao, normalizadas, pelo tratamento, o tonus simpatico (-24,5 ± 3 bpm, p <0,01) e o tonus vagal (110 ± 9 bpm, p <0,01). O sildenafil tambem foi capaz de reduzir o estresse oxidativo sistemico nos ratos 2R1C, quando comparado com os animais 2R1C + salina (1,04±0,07 vs. 1,67±0,08). O tratamento com sildenafil melhorou o controle barorreflexo da pressao arterial, por meio da correcao do desbalanco autonomico e reducao do estresse oxidativo.
  • ALYNNE CARVALHO GALVÃO
  • A INIBIÇÃO CENTRAL DO TNF-α REDUZ A PRESSÃO ARTERIAL VIA INIBIÇÃO DO TÔNUS SIMPÁTICO EM RATOS COM HIPERTENSÃO RENOVASCULAR.
  • Fecha: 20-jun-2016
  • Hora: 14:00
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  • Ao longo dos anos, evidencias sugerem uma relacao entre a angiotensina II e citocinas pro-inflamatorias, como o TNF-α, na patogenese de doencas cardiovasculares, tais como a hipertensao arterial. Recentemente, o foco de novos estudos tem sido compreender os mecanismos centrais envolvidos na manutencao de eventos que desencadeiam o aumento da atividade simpatica durante a hipertensao. O objetivo deste estudo foi avaliar os efeitos da inibicao central do TNF-α sobre a pressao arterial, o tonus simpatico, a sensibilidade do barorreflexo e o estresse oxidativo no RVLM de ratos com hipertensao renovascular (2R1C). Um clipe de prata (diametro interno = 0,2mm) foi implantado na arteria renal direita para inducao da hipertensao (por seis semanas). Os animais foram divididos em tres grupos, Sham, 2R1C e 2R1C+PTX. Este ultimo grupo recebeu infusao central (no ventriculo lateral) de pentoxifilina (30 nmol/uL/h), um inibidor do TNF-α, por minibombas osmoticas durante 14 dias, quatro semanas apos a implantacao do clipe de prata. Cateteres foram implantados na aorta abdominal e veia cava caudal de animais de todos os grupos para o registro dos parametros cardiovasculares e administracao de drogas, respectivamente. Fenilefrina (8 μg/kg, i.v.) e nitroprussiato de sodio (25 μg/kg, i.v.) foram administrados para avaliacao da sensibilidade do barorreflexo, o qual tambem foi avaliado por meio do metodo de sequencias para barorreflexo espontaneo (Cardioseries v.2.4). Uma avaliacao indireta da modulacao autonomica da resistencia vascular foi realizada com analise espectral do componente simpatico de baixa frequencia (LF) da pressao arterial sistolica (PAS) (CardioSeries v.2.4), enquanto o tonus simpatico vascular foi avaliado mediante o bloqueio ganglionar por hexametonio (30 mg/kg, i.v). A medida do acumulo de superoxido no RVLM dos animais foi feita pela tecnica do diidroetidio (DHE), e expressa pela fluorescencia relativa (unidades arbitrarias). O grupo 2R1C apresentou aumento na pressao arterial media (PAM) em comparacao ao grupo Sham (171 ± 11 vs. 113 ± 5 mmHg; n= 8; p < 0.05). Os animais hipertensos apresentaram diminuicao na sensibilidade do barorreflexo em relacao aos animais normotensos na analise pelo metodo de Oxford (-1,30 ± 0,10 vs. -2,59 ± 0,17 bpm.mmHg−1 ; n = 8; p < 0.05) e pelo metodo de sequencias (0.58 ± 0,08 vs. 1.48 ± 0,04 ms/mmHg; n = 8; p<0.05). Quanto a avaliacao da atividade vasomotora simpatica por analise espectral, os animais 2R1C apresentaram aumento do componente LF em relacao ao grupo Sham (9,16 ± 0,52 vs. 3,32 ± 0,38 mmHg2 ; n = 8; p<0.05). O aumento tambem foi observado em animais 2R1C comparados aos normotensos em relacao a variacao da PAM apos bloqueio com hexametonio (-60 ± 5 vs. -33 ± 2 ΔmmHg; n = 8; p < 0.05) e ao acumulo de superoxido no RVLM (18 ± 2 vs. 4 ± 1; n = 8; p < 0.05). Quando comparado ao grupo 2R1C que nao recebeu infusao de pentoxifilina (n=8), a inibicao central do TNF-α por 14 dias em animais com hipertensao renovascular (n=6) reduziu a pressao arterial media (171 ± 11 vs. 131 ± 2 mmHg; p <0.05) e o acumulo de superoxido no RVLM (18 ± 2 vs. 8 ± 1; p < 0.05). Alem disso, animais do grupo 2R1C+PTX apresentaram melhora na sensibilidade do barorreflexo e reducao do tonus simpatico quando comparado ao grupo 2R1C (-34 ± 3 vs. -60 ± 5 ΔmmHg, n=8; p< 0.05). Adicionalmente, a analise espectral do LF (PAS) mostrou que a inibicao central do TNF-α reduziu esse componente no grupo 2R1C+PTX em relacao ao grupo 2R1C (4,90 ± 0,66 vs. 9.16 ± 0,52 mmHg2 ; p < 0.05). Baseado em nossos resultados, sugerimos o envolvimento do TNF-α na manutencao da atividade vasomotora simpatica e no estresse oxidativo na regiao do RVLM no modelo de hipertensao renovascular (2R1C).
  • JOSÉ GUILHERME FERREIRA MARQUES GALVÃO
  • PAPEL DA OUABAÍNA NA INFLAMAÇÃO ALÉRGICA PULMONAR: ASPECTOS FENOTÍPICOS E FUNCIONAIS.
  • Fecha: 16-jun-2016
  • Hora: 09:00
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  • A ouabaina (OUA), um potente inibidor da Na+/K+ ATPase, foi identificada como uma substancia endogena presente no plasma humano. Nos ultimos anos, foi evidenciado que a OUA e capaz de interferir em diversos aspectos do sistema imunologico e em diferentes modelos de inflamacao, porem o seu efeito na inflamacao alergica pulmonar nao tinha sido investigado previamente. Processos inflamatorios alergicos das vias aereas inferiores sao caracterizados por migracao celular e hiperresponsividade bronquica, em decorrencia da sensibilizacao por antigenos proteicos como a ovalbumina (OVA). Objetivo: Avaliar o efeito da ouabaina no modelo de inflamacao alergica pulmonar induzida por OVA. Metodos: Camundongos BALB/c femeas (n = 6) foram sensibilizados e desafiados com OVA e pre-tratados via intraperitoneal (i.p.) com OUA (0,56 mg/kg) dois dias antes das sensibilizacoes e uma hora antes destas, ou com dexametasona (2 mg/kg) subcutanea 1 hora antes de cada desafio. Parametros da inflamacao alergica, como migracao celular e producao de citocinas no fluido do lavado broncoalveolar (BALF), producao de muco e remodelamento histopatologico pulmonar quantificacao de IgE serica, foram analisados posteriormente. Resultados: A ouabaina reduziu em 60% o numero total de celulas presentes no BALF como um reflexo da inibicao de leucocitos polimorfonucleares e linfocitos T CD3+, bem como a producao de citocinas do fenotipo Th2, IL-4 e IL-13. Ademais, a ouabaina reduziu os parametros inflamatorios histopatologicos, como hiperplasia das celulas caliciformes com consequente diminuicao de muco, alem de reduzir o titulo de OVA-IgE especifica. Conclusao: Estes dados sugerem que a OUA apresenta efeito anti-inflamatoria no modelo de inflamacao alergica pulmonar, modulando parametros do fenotipo Th2.