HERALDO POSSOLO DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Anti-Atherogenic Effects of a Phenol-Rich Fraction from Brazilian Red Wine (Vitis labrusca L.) in Hypercholesterolemic Low-Density Lipoprotein Receptor Knockout Mice(2012) HORT, Mariana Appel; SCHULDT, Elke Zuleika; BET, Angela Cristina; DALBO, Silvia; SIQUEIRA, Jarbas Mota; IANSSEN, Carla; ABATEPAULO, Fatima; SOUZA, Heraldo Possolo de; VELEIRINHO, Beatriz; MARASCHIN, Marcelo; RIBEIRO-DO-VALLE, Rosa MariaModerate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr-/- mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.
- Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin(2012) PESARO, Antonio Eduardo P.; SERRANO JR., Carlos V.; FERNANDES, Juliano L.; CAVALCANTI, Alexandre B.; CAMPOS, Alexandre H.; MARTINS, Herlon S.; MARANHAO, Raul C.; LEMOS, James A. de; SOUZA, Heraldo P.; NICOLAU, Jose C.Background: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. Objective: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10 mg/simvastatin 20 mg (E10/S20) with simvastatin 80 mg (S80). Methods and results: CAD patients (n = 83, 63 +/- 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 +/- 13% vs. 28 +/- 30%, p = 0.46), apo-B (18 +/- 17% vs. 22 +/- 15%, p = 0.22) and oxidized LDL (15 +/- 33% vs. 18 +/- 47%, p = 0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 +/- 43% vs. 8 +/- 33%, p = 0.02). Conclusions: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4x less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.
conferenceObject Late remodeling of extracellular matrix after acute inflammatory injury or chronic distension(2012) PRIST, Iryna Hirata; SALLES, Alessandra Grassi; SALGADO, Thais M. de Lima; SOUZA, Heraldo Possolo DeExtracellular matrix remodeling is a crucial step in the healing process after inflammatory or infectious insult. We studied the role of matrix metalloproteinases in models of disease secondary to an acute inflammatory injury (burned skin) or chronic aggression (skin from obese patients submitted to gastroplasty). Skin samples were extracted using a 4 mm punch from abdomen of patients in late post-operative of bariatric surgery, recovered from third degree burns or control subjects. RNA was extracted by TRIzol and evaluated by quantitative PCR. MMPs activity was determined by zymography. In skin from burned patients, MMPs 2 and 9 expression was not different from control subjects. Obese patients present a higher MMP2 expression, compared to controls (2.4±0.56 x 1.0±0.1, respectively, p<0.05), however MMP9 mRNA was not detectable in these patients, even when conventional PCR was used. Interestingly, in spite of higher mRNA amounts, MMP2 activity was reduced in burned patients compared to controls (1.3±0.1 x 2.6±0.5 A.U., respectively, p<0.05), while MMP9 activity had a large variability, preventing any conclusion. We conclude that an acute inflammatory stimulus leads to late decreased MMP2 activity, what can explain the extensive fibrosis observed in these patients. In a more prolonged injury, due to chronic skin distension caused by obesity, MMP9 expression is affected leading to flabby skin deposits.- Nitric Oxide Activates p21(ras) by S-Nitrosylation during Loss of Integrin-Mediated Cell-Matrix Contact Leading to Increased Superoxide Level and Cell Survival(2012) MELO, Fabiana Henriques; MOLOGNONI, Fernanda; MORETTI, Ana; SOUZA, Heraldo Possolo de; JASIULIONIS, Miriam Galvonas
- Circulating fatty acid binding protein as a marker of intestinal failure in septic patients(2012) MACHADO, Marcel Cerqueira Cesar; BARBEIRO, Hermes Vieira; SILVA, Fabiano Pinheiro da; SOUZA, Heraldo Possolo de
conferenceObject Effect of low level laser therapy on acute lung injury(2012) CURY, Vivian; LIMA-SALGADO, Thais; PINHEIRO, Natalia; PRADO, Carla Maximo; ASSIS, Livia; MORETTI, Ana Iochabel; SOUZA, Heraldo PossoloLow level laser therapy (LLLT) is prescribed as adjuvant therapy for inflammatory diseases. Hence, we examined whether LLLT may ameliorate acute lung injury (ALI) induced by intratracheal LPS instillation. C57 black mice (n=10 per group) were treated with intratracheal LPS (5mg/kg) or PBS. Six hours after instillation, two groups (PBS and LPS) were irradiated with laser at 660 nm, power output 30mW, fluency 10J/cm2. We observed a marked decrease in the number of cells recovered by bronchoalveolar lavage in LPS + LLLT animals compared to LPS alone (2.0±0.8 x 4.4±1.3, respectively p<0.05). LLLT also decreased the number of inflammatory cells infiltrated in lung interstitium (49.6±3.15 x 71.8±3.92), p<0.05). There was also a decrease in the expression of F4/80 (macrophage surface marker) and MCP-1 (monocyte chemoattractant protein-1), detected by quantitative PCR, in animals submitted to LPS + LLLT, when compared to animals that received only LPS. A marked decrease in cytokines secretion (IL1β, TNFα, IL6, IL10) was also observed in LPS+LLLT group. No difference was observed in animals that received PBS, regardless of LLLT. Therefore, LLLT decreases pulmonary inflammatory cell infiltration, cytokines and chemokines secretion in an experimental model of ALI, supporting the notion that laser therapy attenuates inflammatory intensity, what can contribute to accelerate ALI resolution.conferenceObject Expression of peroxisome proliferator activated receptor gamma coactivator 1 (PGC-1) on the immune response to bacteria(2012) NERO, Luis Guilherme Del; MARTA, Guilherme; LIMA-SALGADO, Thais; KUBO, Sueli; LLIMONA, Flavia; VELASCO, Irineu Tadeu; SOUZA, HeraldoIntroduction/Objective: Inflammatory response during sepsis requires energy expenditure from immune cells. Since the transcription coactivator PGC-1 controls cell energy homeostasis, we aimed to determine whether PGC-1 may modulate the immune response in an experimental model of sepsis. Methods: Live bacteria were injected intraperitoneally in Balb/C mice and PGC-1β expression was evaluated by quantitative PCR in peritoneal macrophages. Further, mice (20 animals in each group) were submitted to cecal ligation and puncture (CLP). Group 1 received intraperitoneal injections of antisense oligonucleotide (ASO) against PGC-1β (3,0 nmol) three days before and three days after CLP. Group 2 was given no specific treatment. The animals were followed for 72 hours and mortality was evaluated every 12 hours. Results: Increased PGC-1β expression was observed in macrophages from animals exposed to bacteria compared to controls (2.7±0.5 vs. 1.0±0.2, respectively, p<0.05). We further evaluated whether PGC-1β absence would interfere with the response to acute bacterial aggression in vivo. Mice from Group 1, where PGC-1β expression was blocked, showed an 80% mortality after 72 hours, while animals from Group 2 had a mortality rate of 63% (p=0,7714). Conclusions: PGC-1β is up-regulated during bacterial infection, however, abolishing PGC-1β expression did not affect mortality of septic mice.- Reposição volêmica com soluções salinas em pancreatite e perfil hepático de proteínas apoptóticas e de choque térmico(2012) RIOS, Ester Correia Sarmento; MORETTI, Ana Iochabel Soares; SOUZA, Heraldo Possolo de; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaOBJECTIVE: Liver failure can occur as a consequence of the systemic inflammation after acute pancreatitis. We assessed the effect of volume repositioning with hypertonic saline solution or normal saline on hepatic cytokine production and the expression of heat-shock proteins and apoptotic proteins after acute pancreatitis. METHODS: Wistar rats were divided in four groups: C - control animals that were not subjected to insult or treatment; NT - animals that were subjected to acute pancreatitis and received no treatment; normal saline - animals that were subjected to acute pancreatitis and received normal saline (NaCl 0.9%); and HS - animals that were subjected to acute pancreatitis and received hypertonic saline solution (NaCl 7.5%). Acute pancreatitis was induced by retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct. At 4, 12 and 24 h following acute pancreatitis induction, TNF-alpha, IL-1-beta, IL-6 and IL-10, caspase-2 and -7, Apaf-1, AIF and HSP60 and 90 were analyzed in the liver. RESULTS: Casp2 decreased in the normal saline and hypertonic saline groups (p<0.05 versus. C) at 12 h. Apaf-1, AIF and HSP90 remained unchanged. At 4 h, Casp7 increased in the NT group (p<0.01 versus C), although it remained at the baseline levels in the reperfused groups. HSP60 increased in all of the groups at 4 h (p< 0.001 vs. C). However, the hypertonic saline group showed lower expression of HSP60 than the normal saline group (p<0.05). Hypertonic saline solution maintained the production of cytokines at normal levels. Volume reperfusion with normal or hypertonic saline significantly modulated the expression of Casp7. CONCLUSION: Volume replacement with hypertonic or normal saline was effective in reducing caspase 7. However, only hypertonic solution was capable of regulating cytokine production and HSP60 expression at all time points.
- Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion(2012) ASSIS, Livia; MORETTI, Ana I. S.; ABRAHAO, Thalita B.; CURY, Vivian; SOUZA, Heraldo P.; HAMBLIN, Michael R.; PARIZOTTO, Nivaldo A.Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n?=?20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808?nm, tip area of 0.00785?cm2, power 30?mW, application time 47?seconds, fluence 180?J/cm2; 3.8?mW/cm2; and total energy 1.4?J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-k beta and COX-2 and by TNF-a and IL-1 beta concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. Lasers Surg. Med. 44: 726735, 2012. (c) 2012 Wiley Periodicals, Inc.
- Nitric oxide modulates metalloproteinase-2, collagen deposition and adhesion rate after polypropylene mesh implantation in the intra-abdominal wall(2012) MORETTI, Ana I. S.; PINTO, Francisco J. P. Souza; CURY, Vivian; JURADO, Marcia C.; MARCONDES, Wagner; VELASCO, Irineu T.; SOUZA, Heraldo P.Prosthetic meshes are commonly used to correct abdominal wall defects. However, the inflammatory reaction induced by these devices in the peritoneum is not completely understood. We hypothesized that nitric oxide (NO), produced by nitric oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall in wild-type and NOS2-deficient (NOS2(-/-)) mice. After 15 days tissues around the mesh implant were collected, and inflammatory markers (the cytokine interleukin 1 beta (IL-1 beta) and NO) and tissue remodeling (collagen and metalloproteinases (MMP) 2 and 9) were analyzed. The lack of NOS2-derived NO induced a higher incidence of visceral adhesions at the mesh implantation site compared with wild-type mice that underwent the same procedure (P < 0.05). Additionally, higher levels of IL-1 beta were present in the mesh-implanted NOS2(-/-) animals compared with control and wild-type mice. Mesh implantation induced collagen I and III deposition, but in smaller amounts in NOS2(-/-) mice. MMP-9 activity after the surgical procedure was similarly increased in both groups. Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but was significantly increased in NOS2(-/-) mice (P < 0.01), due to decreased S-nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is crucial for an adequate response to and integration of polypropylene mesh implants in the peritoneum. NO deficiency results in a prolonged inflammatory reaction to the mesh implant, and reduced collagen deposition may contribute to an increased incidence of visceral adhesions.