IRINEU TADEU VELASCO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure(2013) ISSA, Victor S.; ANDRADE, Lucia; AYUB-FERREIRA, Silvia M.; BACAL, Fernando; BRAGANCA, Ana C. de; GUIMARAES, Guilherme V.; MARCONDES-BRAGA, Fabiana G.; CRUZ, Fatima D.; CHIZZOLA, Paulo R.; CONCEICAO-SOUZA, Germano E.; VELASCO, Irineu T.; BOCCHI, Edimar A.Background: Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. Methods: In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100 mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serumcreatinine of 0.3 mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP(2)), urea transporter (UT-A(1)), and sodium/hydrogen exchanger 3 (NHE3). Results: Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. Conclusions: HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.
- Septic shock in older people: a prospective cohort study(2013) SILVA, Fabiano Pinheiro da; ZAMPIERI, Fernando Godinho; BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; GOULART, Alessandra Carvalho; TORGGLER FILHO, Francisco; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarBackground: Septic shock is the first cause of death in Intensive Care Units. Despite experimental data showing increased inflammatory response of aged animals following infection, the current accepted hypothesis claims that aged patients are immunocompromised, when compared to young individuals. Results: Here, we describe a prospective cohort study designed to analyze the immune profile of this population. Conclusion: Older people are as immunocompetent as the young individual, regarding the cytokines, chemokines and growth factors response to devastating infection.
- Decreased Parathyroid Hormone Levels Despite Persistent Hypocalcemia in Patients with Kidney Failure Recovering from Septic Shock(2013) SILVA, Fabiano Pinheiro da; ZAMPIERI, Fernando Godinho; BARBEIRO, Hermes Vieira; TORGGLER FILHO, Francisco; GOULART, Alessandra Carvalho; JORGETTI, Vanda; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo deIntroduction: Hypocalcemia is a common and poorly understood finding in critically ill patients. The current study was designed to assess the association of ionized calcium, vitamin D, phosphorus and Parathyroid hormone levels in a cohort of patients with and without kidney dysfunction admitted for sepsis or non-infectious causes. Methods: Prospective cohort clinical and biochemical study. Results: We confirmed that hypocalcemia and hypovitaminosis D are a common finding in critically ill patients. Parathyroid hormone levels significantly rise in septic shock. In the recovery phase, however, despite persistent hypocalcemia, Parathyroid hormone levels abruptly decrease in patients with kidney dysfunction, but not in patients with normal renal function. Conclusions: The systemic inflammatory response syndrome probably leads to inappropriately high Parathyroid hormone levels during septic shock. In the recovery phase, Parathyroid hormone levels decrease, but calcium levels remain low, displaying evidence that the parathyroid is not responding as expected. Since Parathyroid hormone receptors and calcium-sensing receptors have been described in immune cells and other cell types, we propose that these effects may have a plethora of other deleterious effects, with important implications to the pathogenesis of septic shock.
- Effects of terlipressin and naloxone compared with epinephrine in a rat model of asphyxia-induced cardiac arrest(2013) MARTINS, Herlon S.; KOIKE, Marcia K.; VELASCO, Irineu T.OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 mu g/kg (TP50; n = 7), 100 mu g/kg (TP100; n = 7) and 150 mu g/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine.
- Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock(2013) BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; ZAMPIERI, Fernando Godinho; MACHADO, Marcel Cerqueira Cesar; TORGGLER FILHO, Francisco; CUNHA, Debora Maria Gomes; GOULART, Alessandra Carvalho; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo de; SILVA, Fabiano Pinheiro daHost defense peptides are ancient weapons of the innate immunity. The human cathelicidin LL-37 protects the epithelial barrier against infection and is constitutively secreted in the bloodstream by immune cells. Current knowledge claims that LL-37 is up regulated upon infection. LL-37 can protect against bacterial infections and possesses many immunomodulatory properties. Here, we show that the human host defense peptide LL-37 is down regulated during septic shock. Furthermore, we show that these effects are not related to vitamin D serum levels, a potent inducer of LL-37 gene expression, pointing out the complex regulation of cathelicidins during septic shock.
- HLA-A*31 como marcador de suscetibilidade genetica em sepse(2013) SILVA, Fabiano Pinheiro da; PREUHS FILHO, Germano; FINGER, Eduardo; BARBEIRO, Hermes Vieira; ZAMPIERI, Fernando Godinho; GOULART, Alessandra Carvalho; TORGGLER FILHO, Francisco; PANAJOTOPOULOS, Nicolas; VELASCO, Irineu Tadeu; KALIL, Jorge; SOUZA, Heraldo Possolo de; CRUZ NETO, Luiz Monteiro da; RODRIGUES, HelcioObjective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis.
- Neutrophils LL-37 migrate to the nucleus during overwhelming infection(2013) SILVA, Fabiano Pinheiro da; MEDEIROS, Maria Cristina Rodrigues; SANTOS, Angela Batista Gomes dos; FERREIRA, Marcelo Alves; GARIPPO, Ana Lucia; CHAMMAS, Roger; CALDINI, Elia; VELASCO, Irineu Tadeu; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarLL-37 is the only cathelicidin produced by human cells. It is secreted by a variety of cell types, including monocyte/macrophages, neutrophils, mast cells, keratinocytes and epithelial cells, acting on the extracellular milieu by directly killing bacteria or boosting innate immunity. Here, we show that LL-37 translocates to the nucleus following overwhelming infection, putting in evidence that its role may be even broader, with new potential important implications to cell biology. Future studies are necessary to address if LL-37 is able to induce or affect transcription, since it can lead to a novel cell signaling pathway that probably will contribute to the understanding of complex diseases.
bookPart Resposta inflamatória sistêmica e caquexia no paciente oncológico(2013) SILVA, Fabiano Pinheiro da; VELASCO, Irineu Tadeu- Neuropeptides in sepsis: From brain pathology to systemic inflammation(2013) SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira Cesar; VELASCO, Irineu TadeuSeptic encephalopathy is frequently diagnosed in critically ill patients and in up to 70% of patients with severe systemic infection [19]. The syndrome is defined by diffuse cerebral dysfunction or structural abnormalities attributed to the effects of systemic infection, rather than a direct central nervous system cause. The clinical characteristics can range from mild delirium to deep coma, but patients are often medically sedated making the diagnosis difficult. Any manifestation, however, is specific and markers of disease are lacking [43]. Sepsis survivors present long term cognitive impairment, including alterations of memory, attention and concentration [10,54]. Here, we propose that neuropeptides may play a key role in septic encephalopathy, leading to a vicious circle characterized by brain disease and systemic inflammation.
- Hypertonic Saline Solution Drives Neutrophil from Bystander Organ to Infectious Site in Polymicrobial Sepsis: A Cecal Ligation and Puncture Model(2013) THEOBALDO, Mariana Cardillo; LLIMONA, Flavia; PETRONI, Ricardo Costa; RIOS, Ester Correia Sarmento; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaThe effects of hypertonic saline solution (HSS) have been shown in several animal models of ischemia and shock. Literature has shown potential benefits of HSS modulating inflammatory response after sepsis in an animal model. We studied the HSS effects in sepsis through cecal ligation and puncture (CLP) in Balb-C mice. Groups studied: 1-CLP without treatment (CLP-C); 2-CLP treated with normal saline solution NaCl 0.9% - 34 ml/Kg (CLP-S); 3-CLP treated with HSS NaCl 7.5% - 4 ml/Kg (CLPH); and 4-group (Basal) without no CLP or treatment. Volume infusion was always applied 30 min after CLP. Lung and peritoneal lavage were harvested after 6h and 24h of CLP to analyze cytokines amount, oxide nitric, lipid peroxidation and neutrophil infiltration. Neutrophil infiltration, ICAM-1, CXCR-2, and CXCL-1 in lung were reduced by HSS (CLP-H) compared to CLP-C or CLP-S. Neutrophil in peritoneal lavage was increased in 24h with HSS (CLP-H) compared to CLP and CLP-S. Peritoneal CXCR-2 was increased in CLP-C and CLP-S but presented a lower increase with HSS (CLP-H) after 6 hours. GRK-2 presented difference among the groups at 24 h, showing a profile similar to neutrophil infiltration. Pro-inflammatory cytokines (TNF-alpha and IL-6) were reduced by HSS treatment; CLP-S increased TNF-alpha IL-10 was increased in lung tissue by the HSS treatment. The oxidative stress (TBARS and nitric oxide biochemistry markers) was reduced with HSS. Animal survival was 33.3% in CLP-C group, 46.6% in CLP-S group and 60% in the CLP-H group after the sixth day. The HSS protects the animal against sepsis. Our results suggest that the volume replacement modulate pro and anti-inflammatory mediators of an inflammatory response, but HSS presented a more effective and potent effect.