VERA LUIZA CAPELOZZI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
190 resultados
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- A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome(2022) FERNANDES, Marcos V. S.; ROCHA, Nazareth N.; FELIX, Nathane S.; RODRIGUES, Gisele C.; SILVA, Luisa H. A.; COELHO, Mariana S.; FONSECA, Ana Carolina F.; TEIXEIRA, Ana Carolina G. M.; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; MARINI, John J.; ROCCO, Patricia R. M.Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24 h, Wistar rats (n = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: 1) 3 cmH(2)O for 2 h (control); 2) 3 cmH(2)O for 1 h followed by an abrupt increase to 9 cmH(2)O for 1 h (no adaptation time); 3) 3 cmH(2)O for 30 min followed by a gradual increase to 9 cmH(2)O over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmH(2)O to 9 cmH(2)O over 1 h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared with the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared with other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (P = 0.002) and shorter adaptation time (P = 0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure. NEW & NOTEWORTHY In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.
- A long-term prospective randomized controlled study of non-specific interstitial pneumonia (NSIP) treatment in scleroderma(2011) DOMICIANO, Diogo S.; BONFA, Eloisa; BORGES, Claudia T. L.; KAIRALLA, Ronaldo A.; CAPELOZZI, Vera L.; PARRA, Edwin; CHRISTMANN, Romy BeatrizThe association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP). Objectives: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment. Methods: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO-Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment. Results: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups. Conclusions: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy.
- Expression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary Hyperhidrosis(2013) MOURA JUNIOR, Nabor B. de; DAS-NEVES-PEREIRA, Joao C.; OLIVEIRA, Flavio R. G. de; JATENE, Fabio B.; PARRA, Edwin R.; CAPELOZZI, Vera L.; WOLOSKER, Nelson; CAMPOS, Jose R. M. deBackground. The pathophysiologic characteristics of primary hyperhidrosis are not well understood and seem to be related to a sympathetic nervous system dysfunction. The resection of thoracic sympathetic chain ganglia is the most effective treatment for hyperhidrosis; however sympathetic ganglia function in normal individuals and in patients with hyperhidrosis is unknown. Methods. A cross-sectional study, in which 2 groups of 20 subjects were analyzed: the hyperhidrosis group (HYP), comprised of patients with hyperhidrosis who were eligible for thoracic sympathectomy, and the control group (CON) comprised of brain-dead organ donors without a history of hyperhidrosis. For each subject, the following were performed: resection of the third left sympathetic ganglion, measurement of the ganglion's diameter, and immunohistochemical evaluation by quantification of strong and weak expression areas of primary antibodies against acetylcholine and alpha-7 neuronal nicotinic receptor subunit. Results. The presence of a strong alpha-7 subunit expression area was 4.85% in patients with primary hyperhidrosis and 2.34% in controls (p < 0.001), whereas the presence of a weak expression area was 11.48% in the HYP group and 4.59% in the CON group (p < 0.001). Strong acetylcholine expression was found in 4.95% of the total area in the HYP group and in 1.19% in the CON group (p < 0.001), whereas weak expression was found in 18.55% and 6.77% of the HYP and CON groups, respectively (p < 0.001). Furthermore, diameter of the ganglia was 0.71 cm in the HYP group and 0.53 cm in the CON group (p < 0.001). Conclusions. There is a higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis. Furthermore, the diameter of the thoracic sympathetic chain ganglia is larger in such patients. (Ann Thorac Surg 2013;95:465-71) (c) 2013 by The Society of Thoracic Surgeons
- Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis(2013) PARRA, E. R.; AGUIAR, A. C. Junior; SILVA, L. O.; SOUZA, H. S. P.; ESPINOZA, J. D.; CAPELOZZI, V. L.Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc- NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.
- Early and late acute lung injury and their association with distal organ damage in murine malaria(2013) SOUZA, Mariana C.; SILVA, Johnatas D.; PADUA, Tatiana A.; CAPELOZZI, Vera Luiza; ROCCO, Patricia R. M.; HENRIQUES, Maria das GracasSevere malaria is characterised by cerebral oedema, acute lung injury (ALI) and multiple organ dysfunctions, however, the mechanisms of lung and distal organ damage need to be better clarified. Ninety-six C57BL/6 mice were injected intraperitoneally with 5 x 10(6) Plasmodium berghei ANKA-infected erythrocytes or saline. At day 1, Plasmodium berghei infected mice presented greater number of areas with alveolar collapse, neutrophil infiltration and interstitial oedema associated with lung mechanics impairment, which was more severe at day 1 than day 5. Lung tumour necrosis factor-alpha and chemokine (C-X-C motif) ligand 1 levels were higher at day 5 compared to day 1. Lung damage occurred in parallel with distal organ injury at day 1; nevertheless, lung inflammation and the presence of malarial pigment in distal organs were more evident at days. In conclusion, ALI develops prior to the onset of cerebral malaria symptoms. Later during the course of infection, the established systemic inflammatory response increases distal organ damage.
- Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort(2023) MACHADO-RUGOLO, J.; BALDAVIRA, C. M.; PRIETO, T. G.; OLIVIERI, E. H. R.; FABRO, A. T.; RAINHO, C. A.; CASTELLI, E. C.; RIBOLLA, P. E. M.; AB'SABER, A. M.; TAKAGAKI, T.; NAGAI, M. A.; CAPELOZZI, V. L.TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early -stage resected EGFR-mutated NSCLC.
- Exercise-Induced Increases in Insulin Sensitivity After Bariatric Surgery Are Mediated By Muscle Extracellular Matrix Remodeling (vol 69, pg 1675, 2020)(2021) DANTAS, Wagner S.; ROSCHEL, Hamilton; MURAI, Igor H.; GIL, Saulo; DAVULURI, Gangarao; AXELROD, Christopher L.; GHOSH, Sujoy; NEWMAN, Susan S.; ZHANG, Hui; SHINJO, Samuel K.; NEVES, Willian das; MEREGE-FILHO, Carlos; TEODORO, Walcy R.; CAPELOZZI, Vera L.; PEREIRA, Rosa Maria; BENATTI, Fabiana B.; SA-PINTO, Ana L. de; CLEVA, Roberto de; SANTO, Marco A.; KIRWAN, John P.; GUALANO, Bruno
- Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome(2018) SANTOS, Raquel S.; MAIA, Ligia de A.; OLIVEIRA, Milena V.; SANTOS, Cintia L.; MORAES, Lillian; PINTO, Eliete F.; SAMARY, Cynthia dos S.; MACHADO, Joana A.; CARVALHO, Anna Carolinna; FERNANDES, Marcos Vinicius de S.; MARTINS, Vanessa; CAPELOZZI, Vera L.; MORALES, Marcelo M.; KOCH, Thea; ABREU, Marcelo Gama de; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia R. M.Background: The authors hypothesized that low tidal volume (V-T) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of V-T and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). Methods: Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different V-T (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (Delta P,(2)(L)/E,(L)) x RR (Delta P,(L) = transpulmonary driving pressure; E,(L) = lung elastance), and was three-fold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. Results: Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high V-T compared to low V-T, in both low (low V-T: 11 [9 to 14], high V-T: 18 [15 to 20]) and high (low V-T: 19 [16 to 25], high V-T: 29 [27 to 30]) power groups. At high V-T, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high V-T than in low V-T. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. Conclusions: In experimental mild ARDS, even at low V-T, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low V-T should be combined with low power.
- Morphometric Analysis of Thoracic Ganglion Neurons in Subjects with and without Primary Palmar Hyperhidrosis(2014) OLIVEIRA, Flavio Roberto Garbelini de; MOURA JR., Nabor B.; CAMPOS, Jose Ribas M. de; WOLOSKER, Nelson; PARRA, Edwin R.; CAPELOZZI, Vera L.; PEGO-FERNANDES, PauloBackground: Hyperhidrosis (HH) is a disease whose physiopathology remains poorly understood and that adversely affects quality of life. There is no morphologic study that includes an adequate control group that allows for comparison of the ganglion of HH to those of normal individuals. The purpose of study was to analyze morphologic and morphometric characteristics of the ganglion from patients with HH and normal individuals (organ donators). Methods: This was a transversal study. The sympathetic thoracic ganglia were obtained from 2 groups of patients. Group PH (palmar hyperhidrosis), 40 patients with palmar HH submitted to surgery by video-assisted thoracoscopy, and group C (control group), 14 deceased individuals (control group of organ donators) without any history of HH. The third left sympathetic thoracic ganglion was resected in all patients. Results: We observed higher number of cells in the PH group than in the control group (14.25 + 3.81 vs. 10.65 + 4.93) with P = 0.007; the mean percentage of ganglion cells stained by caspases-3 in the PH group was significantly greater than that of the C group (2.37 + 0.79 vs. 0.77 + 0.28) with P < 0.001; the mean value of area of collagen in the PH group was 0.80 IQ (0.08-1.87), and in the control group it was 2.36 IQ (0.49-5.98) with P = 0.061. Conclusions: Subjects with primary palmar HH have a higher number of ganglion cells within the ganglion and a higher number of cells in apoptosis. Also, the subjects of PH group have less collagen in the sympathetic ganglion when compared with the control group, but not statistically significant.
- Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury in Rats(2019) FELIX, Nathane S.; SAMARY, Cynthia S.; CRUZ, Fernanda F.; ROCHA, Nazareth N.; FERNANDES, Marcos V. S.; MACHADO, Joana A.; BOSE-MADUREIRA, Rebecca L.; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; MARINI, John J.; ROCCO, Patricia R. M.Background: This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (V T) could be attenuated if V T increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal V T were tested. Methods: Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with V T = 6 ml/kg for 2 h (control); V T = 6 ml/kg during hour 1 followed by an abrupt increase to V T = 22 ml/kg during hour 2 (no adaptation time); V T = 6 ml/kg during the first 30 min followed by a gradual V T increase up to 22 ml/kg for 30 min, then constant V T = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual V T increase, from 6 to 22 ml/ kg during hour 1 followed by V T = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H 2 O. Nonventilated animals were used for molecular biology analysis. Results: At 2 h, diffuse alveolar damage score and heterogeneity index were greater in the longer adaptation time group than in the control and shorter adaptation time animals. Gene expression of interleukin-6 favored the shorter (median [interquartile range], 12.4 [9.1-17.8]) adaptation time compared with longer (76.7 [20.8 to 95.4]; P = 0.02) and no adaptation (65.5 [18.1 to 129.4]) time (P = 0.02) strategies. Amphiregulin, metalloproteinase-9, club cell secretory protein-16, and syndecan showed similar behavior. Conclusions: In experimental mild acute respiratory distress syndrome, lung damage in the shorter adaptation time group compared with the no adaptation time group was attenuated in a time-dependent fashion by preemptive adaptation of the alveolar epithelial cells and extracellular matrix. Extending the adaptation period increased cumulative power and did not prevent lung damage, because it may have exposed animals to injurious strain earlier and for a longer time, thereby negating any adaptive benefit.