FRANCISCO GARCIA SORIANO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
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- The contributions of dipeptidyl peptidase IV to inflammation in heart failure(2016) SALLES, Thiago de Almeida; ZOGBI, Camila; LIMA, Thais Martins de; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; BARBEIRO, Hermes Vieira; ANTONIO, Ednei Luiz; SANTOS, Leonardo dos; PEREIRA, Alexandre da Costa; TUCCI, Paulo Jose Ferreira; FARIA, Daniele de Paula; SORIANO, Francisco Garcia; GIRARDI, Adriana Castello CostaCirculating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-alpha, IL-1 beta, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.
- The Role of Acetylcholine in the Inflammatory Response in Animals Surviving Sepsis Induced by Cecal Ligation and Puncture(2016) JEREMIAS, I. C.; VICTORINO, V. J.; BARBEIRO, H. V.; KUBO, S. A.; PRADO, C. M.; LIMA, T. M.; SORIANO, F. G.The cholinergic anti-inflammatory pathway controls the inflammatory response and nonreflexive consciousness through bidirectional communication between the brain and immune system. Moreover, brain acetylcholinesterase activity may have a role in regulating the vagus nerve in this pathway. Thus, we analyzed the role of acetylcholine (ACh) in the inflammatory response 15 days after induction of sepsis by cecal ligation and puncture (CLP). Balb/c mice were pretreated with or without donepezil (5 mg/kg/day, orally) 7 days before CLP, and mice homozygous for vesicular ACh transporter (VAChT) knockdown (KD) were subjected to CLP. All animals were sacrificed 15 days after CLP, and the plasma, spleen, and hippocampus were collected. Characterization of splenic lymphocytes and cytokine levels in the plasma, spleen, and hippocampus was determined. Our results showed a splenomegaly in group CLP. The numbers of cytotoxic T cells, helper T cells, regulatory T cells, B cells, and Th17 cells differed between mice subjected to CLP and to sham operation in both untreated and donepezil-treated groups. In VAChT-KD mice, CLP resulted in decreased cytotoxic and helper T cells and increased in Th17 cells compared with the sham. Additionally, in VAChT-KD mice, the levels of pro-inflammatory cytokines, such as IL-1 beta, IL-6, and TNF-alpha, were increased following CLP. Thus, we concluded that ACh affected the inflammatory response at 15 days after CLP since stimulation of cholinergic transmission increased the proliferation of lymphocytes, including regulatory T cells, in association with a lower inflammatory profile and VAChT-KD decreased the number of lymphocytes and increased inflammation.
- The role of nitric oxide in the epigenetic regulation of THP-1 induced by lipopolysaccharide(2016) RIOS, Ester Correia Sarmento; LIMA, Thais Martins de; MORETTI, Ana Iochabel Soares; SORIANO, Francisco GarciaAims: Changes in the gene expression are one of the molecular events involved in the Systemic of Inflammatory Response Syndrome during sepsis. The preconditioning with low doses of lipopolysaccharide (LPS) reduces the expression of pro-inflammatory genes leading to less tissue damage and better outcome. This hyporesponsive state called tolerance is associated to alterations in chromatin structure and nitric oxide (NO) production. In the current study, we demonstrated that tolerance induced by LPS was found to be NO-dependent and related to epigenetic changes. Main methods: THP-1 cells were cultivated in RPMI medium(Control), submitted to tolerance (500 ng/mL of LPS 24 h before challenge with 1000 ng/mL of LPS during 24 h Tolerant group) and challenge (1000 ng/mL of LPS during 24 h Directly challenged group). The analyses performed were: cytokines production, histone acetyl transferases/histone deacetylases (HAT/HDAC) activity, nitrosylation of HDAC-2 and -3, expression of acetylated histones H3 and H4. HDAC and Nitric Oxide Synthases (NOS) activities were inhibited with 30 mM trichostatin (TSA) and 100 mu M LNAME, respectively. Key findings: Administration of low doses of LPS repressed the production of IL-6 and IL-10, however this effect was abolished with the inhibition of NOS activity and by TSA in the case of IL-10. Tolerance modulates the activity of HAT and, consequently, the acetylation of histones H3 and H4. Inhibition of NO decreases acetylation of Histones. The HDACs 2 and 3 were nitrosylated after the tolerance induction. Significance: The tolerance to LPS regulates the cytokine production by modulating chromatin structure and this event is NO dependent.
- Quality indicators for enteral and parenteral nutrition therapy: application in critically ill patients ""at nutritional risk""(2016) OLIVEIRA-FILHO, Ronaldo Sousa; RIBEIRO, Lia Mara Kauchi; CARUSO, Lucia; LIMA, Patricia Azevedo de; DAMASCENO, Nagila Raquel Teixeira; SORIANO, Francisco GarciaIntroduction: Quality Indicators for Nutritional Therapy (QINT) allow a practical assessment of nutritional therapy (NT) quality. Objective: To apply and monitor QINT for critically ill patients at nutritional risk. Methods: Cross sectional study including critically ill patients > 18 years old, at nutritional risk, on exclusive enteral (ENT) or parenteral nutritional therapy (PNT) for > 72 hours. After three consecutive years, 9 QINT were applied and monitored. Statistical analysis was performed with SPSS version 17.0. Results: A total of 145 patients were included, 93 patients were receiving ENT, among then 65% were male and the mean age was 55.7 years (+/- 17.4); 52 patients were receiving PNT, 67% were male and the mean age was 58.1 years (+/- 17.4). All patients (ENT and PM) were nutritionally screened at admission and their energy and protein needs were individually estimated. Only ENT was early initiated, more than 70% of the prescribed ENT volume was infused and there was a reduced withdrawal of enteral feeding tube. The frequency of diarrhea episodes and digestive fasting were not adequate in ENT patients. The proper supply of energy was contemplated only for PNT patients and there was an expressive rate of oral intake recovery in ENT patients. Conclusion: After three years of research, the percentage of QINT adequacy varied between 55%-77% for ENT and 60%-80% for PNT. The results were only made possible by the efforts of a multidisciplinary team and the continuous re-evaluation of the procedures in order to maintain the nutritional assistance for patients at nutritional risk.
- Sepsis Induces Telomere Shortening: a Potential Mechanism Responsible for Delayed Pathophysiological Events in Sepsis Survivors?(2016) OLIVEIRA, Naara Mendes; RIOS, Ester C. S.; LIMA, Thais Martins de; VICTORINO, Vanessa Jacob; BARBEIRO, Hermes; SILVA, Fabiano Pinheiro da; SZABO, Csaba; SORIANO, Francisco GarciaSepsis survivors suffer from additional morbidities, including higher risk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 mu l of normal saline intraperitoneally (i.p.) and the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i.p. After 48 h, animals were euthanized to collect blood, spleen and kidney. The human component of our study utilized blood samples obtained from patients in the trauma department and samples collected 7 d later in those patients who developed sepsis. Telomere length was measured by quantitative polymerase chain reaction. Since oxidative stress is a known inducer of telomere shortening, thiobarbituric acid-reactive substances and superoxide dismutase activity were analyzed to evaluate oxidative stress burden. Induction of endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients who progressed to sepsis also exhibited a statistically significant reduction of telomere length. Endotoxemia in mice also induced an early-onset increase in oxidative stress markers but was not associated with a downregulation of telomerase protein expression. We conclude that endotoxemia and sepsis induce telomere shortening in various tissues and hypothesize that this may contribute to the pathogenesis of the delayed pathophysiological events in sepsis survivors.
- Hydrogen sulfide modulates chromatin remodeling and inflammatory mediator production in response to endotoxin, but does not play a role in the development of endotoxin tolerance(2016) RIOS, Ester C. S.; SORIANO, Francisco G.; OLAH, Gabor; GEROE, Domokos; SZCZESNY, Bartosz; SZABO, CsabaBackground: Pretreatment with low doses of LPS (lipopolysaccharide, bacterial endotoxin) reduces the pro-inflammatory response to a subsequent higher LPS dose, a phenomenon known as endotoxin tolerance. Moreover, hydrogen sulfide (H2S), an endogenous gaseous mediator (gasotransmitter) can exert anti-inflammatory effects. Here we investigated the potential role of H2S in the development of LPS tolerance. THP1 differentiated macrophages were pretreated with the H2S donor NaHS (1 mM) or the H2S biosynthesis inhibitor aminooxyacetic acid (AOAA, 1 mM). Methods: To induce tolerance, cells were treated with a low concentration of LPS (0.5 mu g/ml) for 4 or 24 h, and then treated with a high concentration of LPS (1 mu g/ml) for 4 h or 24 h. In in vivo studies, male wild-type and CSE-/- mice were randomized to the following groups: Control (vehicle); Endotoxemic saline for 3 days before the induction of endotoxemia with 10 mg/kg LPS) mg/kg; Tolerant (LPS at 1 mg/kg for 3 days, followed LPS at 10 mg/kg). Animals were sacrificed after 4 or 12 h; plasma IL-6 and TNF-alpha levels were measured. Changes in histone H3 and H4 acetylation were analyzed by Western blotting. Results: LPS tolerance decreased pro-inflammatory cytokine production. AOAA did not affect the effect of tolerance on reducing cytokine production. Treatment of the cells with the H2S donor reduced cytokine production. Induction of the tolerance increased the acetylation of H3; AOAA reduced histone acetylation. H2S donation increased histone acetylation. Tolerance did not affect the responses to H2S with respect to histone acetylation. Conclusions: In conclusion, both LPS tolerance and H2S donation decrease LPS-induced cytokine production in vitro and modulate histone acetylation. However, endogenous, CSE-derived H2S does not appear to play a significant role in the development of LPS tolerance.
- Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury(2016) ALMEIDA, Francine Maria; OLIVEIRA-JUNIOR, Manoel Carneiro; SOUZA, Renato Aparecido; PETRONI, Ricardo Costa; SOTO, Sonia Fatima; SORIANO, Francisco Garcia; CARVALHO, Paulo Tarso Camillo de; ALBERTINI, Regiane; DAMACENO-RODRIGUES, Nilsa Regina; LOPES, Fernanda Degobbi Tenorio Quirino Santos; CASTRO-FARIA-NETO, Hugo Caire; MARTINS, Milton Arruda; DOLHNIKOFF, Marisa; PAZETTI, Rogerio; VIEIRA, Rodolfo PaulaBACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage This study evaluated the effects of Cr supplementation in a model of lung PR. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response. RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleulcin-1 beta (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and antioxidant properties of Cr and modulation of TLRs.
- INCREASED EXPRESSION OF ACTIVATED LY6G+CD11B+CD62L-NEUTROPHILS IN BALB/C MICE WITH PRISTANE INDUCED LUPUS-LIKE DISEASE(2016) UGRIUMOV, N.; GOLDENSTEIN-SCHAINBERG, C.; CARRASCO, S.; MENDES, I. Begalli; LIMA, T. M.; PEIXOTO, T. Vasconcelos; MELLO, S. B. Verissimo de; SORIANO, F. G.
- Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response(2016) FONSECA, Monique T.; RODRIGUES, Abner C.; CEZAR, Luana C.; FUJITA, Andre; SORIANO, Francisco G.; STEINER, Alexandre A.Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0 degrees C for longer than 2 h, with at least one reading of 35.5 degrees C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0 degrees C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation.
- The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice(2016) JEREMIAS, I. C.; VICTORINO, V. J.; MACHADO, J. L.; BARROSO, W. A.; ARIGA, S. K.; LIMA, T. M.; SORIANO, F. G.Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100 beta were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlexA (R) technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100 beta levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1 beta, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100 beta, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of inflammation. Taken together, our data indicate that the severity of sepsis impacts the brain in absence of a change in the spleen lymphocyte profile.