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
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conferenceObject URINARY BIOMARKER NGAL IN PATIENTS WITH HEPATORENAL SYNDROME: ACCURACY STUDY IN PREDICTION OF NO RESPONSE TO THERAPY WITH ALBUMIN AND TERLIPRESSIN(2016) XIMENES, R. O.; HELOU, C.; DINIZ, M.; BARBEIRO, D.; SOUZA, H.; D'ALBUQUERQUE, L. A.; CARRILHO, F.; FARIAS, A.- Effects of diazoxide in experimental acute necrotizing pancreatitis(2017) ANDRADE, Roberta de Oliveira; KUNITAKE, Tiago; KOIKE, Marcia Kiyomi; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloOBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n= 38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p = 0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p = 0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
- Ânion gap corrigido para albumina, fosfato e lactato é um bom preditor de íon gap forte em pacientes enfermos graves: estudo de coorte em nicho(2013) ZAMPIERI, Fernando Godinho; PARK, Marcelo; RANZANI, Otavio Tavares; MACIEL, Alexandre Toledo; SOUZA, Heraldo Possolo de; CRUZ NETO, Luiz Monteiro da; SILVA, Fabiano Pinheiro daOBJECTIVE: Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality. METHODS: We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2mEq/L (low BE group - lBE) and the other in patients with base-excess >-2mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality. RESULTS: There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r2=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r2=0.94) and in the hBE group (r2=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression. CONCLUSION: Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality.
- Applicability of the GLIM criteria for the diagnosis of malnutrition in older adults in the emergency ward: A pilot validation study(2021) FERNANDEZ, Shirley Steffany Munoz; GARCEZ, Flavia Barreto; ALENCAR, Julio Cesar Garcia de; CEDERHOLM, Tommy; APRAHAMIAN, Ivan; MORLEY, John Edward; SOUZA, Heraldo Possolo de; SILVA, Thiago Junqueira Avelino da; RIBEIRO, Sandra Maria LimaBackground & aims: Acutely ill older adults are at higher risk of malnutrition. This study aimed to explore the applicability and accuracy of the GLIM criteria to diagnose malnutrition in acutely ill older adults in the emergency ward (EW). Methods: We performed a retrospective secondary analysis, of an ongoing cohort study, in 165 participants over 65 years of age admitted to the EW of a Brazilian university hospital. Nutrition assessment included anthropometry, the Simplified Nutritional Assessment Questionnaire (SNAQ), the Malnutrition Screening Tool (MST), and the Mini-Nutritional Assessment (MNA). We diagnosed malnutrition using GLIM criteria, defined by the parallel presence of at least one phenotypic [nonvolitional weight loss (WL), low BMI, low muscle mass (MM)] and one etiologic criterion [reduced food intake or assimilation (RFI), disease burden/inflammation]. We used the receiver operating characteristic (ROC) curves and Cox and logistic regression for data analyses. Results: GLIM criteria, following the MNA-SF screening, classified 50.3% of participants as malnourished, 29.1% of them in a severe stage. Validation of the diagnosis using MNA-FF as a reference showed good accuracy (AUC = 0.84), and moderate sensitivity (76%) and specificity (75.1%). All phenotypic criteria combined with RFI showed the best metrics. Malnutrition showed a trend for an increased risk of transference to intensive care unit (OR = 2.08, 95% CI 0.99, 4.35), and severe malnutrition for in-hospital mortality (HR = 4.23, 95% CI 1.2, 14.9). Conclusion: GLIM criteria, following MNA-SF screening, appear to be a feasible approach to diagnose malnutrition in acutely ill older adults in the EW. Nonvolitional WL combined with RFI or acute inflammation were the best components identified and are easily accessible, allowing their potential use in clinical practice.
- Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion(2013) ASSIS, Livia; MORETTI, Ana Iochabel Soares; ABRAHAO, Thalita Balsamo; SOUZA, Heraldo Possolo de; HAMBLIN, Michael R.; PARIZOTTO, Nivaldo AntonioMuscle regeneration is a complex phenomenon, involving replacement of damaged fibers by new muscle fibers. During this process, there is a tendency to form scar tissue or fibrosis by deposition of collagen that could be detrimental to muscle function. New therapies that could regulate fibrosis and favor muscle regeneration would be important for physical therapy. Low-level laser therapy (LLLT) has been studied for clinical treatment of skeletal muscle injuries and disorders, even though the molecular and cellular mechanisms have not yet been clarified. The aim of this study was to evaluate the effects of LLLT on molecular markers involved in muscle fibrosis and regeneration after cryolesion of the tibialis anterior (TA) muscle in rats. Sixty Wistar rats were randomly divided into three groups: control, injured TA muscle without LLLT, injured TA muscle treated with LLLT. The injured region was irradiated daily for four consecutive days, starting immediately after the lesion using an AlGaAs laser (808 nm, 30 mW, 180 J/cm(2); 3.8 W/cm(2), 1.4 J). The animals were sacrificed on the fourth day after injury. LLLT significantly reduced the lesion percentage area in the injured muscle (p < 0.05), increased mRNA levels of the transcription factors MyoD and myogenin (p < 0.01) and the pro-angiogenic vascular endothelial growth factor (p < 0.01). Moreover, LLLT decreased the expression of the profibrotic transforming growth factor TGF-beta mRNA (p < 0.01) and reduced type I collagen deposition (p < 0.01). These results suggest that LLLT could be an effective therapeutic approach for promoting skeletal muscle regeneration while preventing tissue fibrosis after muscle injury.
conferenceObject Intestinal Barrier Dysfunction in Ageing Animals With Acute Pancreatitis: Increased Intestinal Inflammation?(2015) MACHADO, Marcel C.; SILVA, Fabiano Pinheiro da; CUNHA, Debora G.; BARBEIRO, Denise F.; COELHO, Ana Maria M.; SOUZA, Heraldo P.- High-fat diet inhibits PGC-1 alpha suppressive effect on NF kappa B signaling in hepatocytes(2018) BARROSO, Wermerson Assuncao; VICTORINO, Vanessa Jacob; JEREMIAS, Isabela Casagrande; PETRONI, Ricardo Costa; ARIGA, Suely Kunimi Kubo; SALLES, Thiago A.; BARBEIRO, Denise Frediani; LIMA, Thais Martins de; SOUZA, Heraldo Possolo deThe peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1 alpha exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1 alpha expression in mice. In this study, we investigated the role of PGC-1 alpha in the inflammatory changes observed in steatohepatitis induced by high-fat diet. C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-alpha, and IL-1 beta quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NF kappa B nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1 alpha on inflammatory mediators' production by hepatocytes. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1 alpha expression, and marked increase in p65 NF kappa B nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1 alpha expression. The knockdown of PGC-1 alpha content caused an increase in IL-6 expression and release via enhanced I kappa B alpha phosphorylation and subsequent increase of p65 NF kappa B nuclear translocation. High-fat diet induces liver inflammation by inhibiting PGC-1 alpha expression and its suppressive effect in NF kappa B pathway.
conferenceObject TLR4 deficiency increases peroxisomal beta-oxidation in LDL knockout mice livers(2014) FERREIRA, D. F.; SOUZA, H. P. D.; PRIST, I. H.; FIAMONCINI, J.; ARIGA, S. K.; LIMA, T. M. D.- Sodium Taurocholate Induced Severe Acute Pancreatitis in C57BL/6 Mice(2021) SERRA, Mariana B.; KOIKE, Marcia K.; BARBEIRO, Denise F.; MACHADO, Marcel C. C.; SOUZA, Heraldo P. deBiliary acute pancreatitis induction by sodium taurocholate infusion has been widely used by the scientific community due to the representation of the human clinical condition and reproduction of inflammatory events corresponding to the onset of clinical biliary pancreatitis. The severity of pancreatic damage can be assessed by measuring the concentration, speed, and volume of the infused bile acid. This study provides an updated checklist of the materials and methods used in the protocol reproduction and shows the main results from this acute pancreatitis (AP) model. Most of the previous publications have limited themselves to reproducing this model in rats. We have applied this method in mice, which provides additional advantages (i.e., the availability of an arsenal of reagents and antibodies for these animals along with the possibility of working with genetically modified strains of mice) that may be relevant to the study. For acute pancreatitis induction in mice, we present a systematic protocol, with a defined dose of 2.5% sodium taurocholate at an infusion speed 10 mu L/min for 3 min in C57BL/6 mice that reaches its maximal level of severity within 12 h of induction and highlight results with outcomes that validate the method. With practice and technique, the total estimated time, from the induction of anesthesia to the completion of the infusion, is 25 min per animal.
- Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1 alpha and MMP-2(2013) CURY, Vivian; MORETTI, Ana Iochabel Soares; ASSIS, Livia; BOSSINI, Paulo; CRUSCA, Jaqueline de Souza; BENATTI NETO, Carlos; FANGEL, Renan; SOUZA, Heraldo Possolo de; HAMBLIN, Michael R.; PARIZOTTO, Nivaldo AntonioIt is known that low level laser therapy is able to improve skin flap viability by increasing angiogenesis. However, the mechanism for new blood vessel formation is not completely understood. Here, we investigated the effects of 660 nm and 780 nm lasers at fluences of 30 and 40 J/cm(2) on three important mediators activated during angiogenesis. Sixty male Wistar rats were used and randomly divided into five groups with twelve animals each. Groups were distributed as follows: skin flap surgery non-irradiated group as a control; skin flap surgery irradiated with 660 nm laser at a fluence of 30 or 40 J/cm(2) and skin flap surgery irradiated with 780 nm laser at a fluence of 30 or 40 J/cm(2). The random skin flap was performed measuring 10 x 4 cm, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was performed on 24 points covering the flap and surrounding skin immediately after the surgery and for 7 consecutive days thereafter. Tissues were collected, and the number of vessels, angiogenesis markers (vascular endothelial growth factor, VEGF and hypoxia inducible factor, HIF-1 alpha) and a tissue remodeling marker (matrix metalloproteinase, MMP-2) were analyzed. LLLT increased an angiogenesis, HIF-1 alpha and VEGF expression and decrease MMP-2 activity. These phenomena were dependent on the fluences, and wavelengths used. In this study we showed that LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1 alpha expression in a dose dependent manner.