Leandra N Z Ramalho

University of São Paulo, São Paulo, Estado de Sao Paulo, Brazil

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Publications (70)107.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction. Few studies have evaluated the factors involved in the spontaneous HBsAg seroclearance in patients with chronic hepatitis B (HBV) followed up on a long-term basis from areas with a low prevalence of HBV infection. We aimed to determine the rate of spontaneous HBsAg seroclearance and the factors related to it in patients with chronic HBV infection followed up at the Hepatitis Outpatient Clinic of HCFMRP from 1992-2008. Materials and methods. A total of 548 patients with chronic HBV infection (366 with chronic hepatitis B and 182 inactive carriers) were followed for 15 years and 9 months with an annual measurement of HBV-DNA, ALT, AST and GGT (average of 4 annual determinations) and serology (HBsAg, HBeAg, Anti-HBeAg and Anti-HBsAg). Results. Spontaneous HBsAg seroclearance occurred in 40 patients (7.3%) with a mean age of 46.0 ± 14.4 years, corresponding to an annual rate of 0.7%.The factors related to spontaneous HBsAg seroclearance were inactive carrier status (67.5 vs. 32.5%, p = 0.000191) and age of more than 40 years (p = 0.0007). There was no difference in the rate of spontaneous HBsAg seroclearance when comparing males and females (p = 0.383). Patients with spontaneous HBsAg seroclearance did not progress to more severe forms of the disease during follow-up. Conclusion. Spontaneous HBsAg seroclearance has a favorable long-term prognosis in patients with chronic HBV infection. HBsAg seroclearance occurred at rates compatible with low prevalence areas and was associated with low serum HBV-DNA levels and an age older than 40 years.
    Annals of hepatology. 11/2014; 13(6):762-70.
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    ABSTRACT: C-type natriuretic peptide (CNP) and nitric oxide (NO) are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3) contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.
    PLoS ONE 01/2014; 9(5):e95446. · 3.53 Impact Factor
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    ABSTRACT: The purpose from this study was to investigate the consequences of sensory neurocompensation to carotid balloon injury in diabetic rats on angiotensin II-induced contraction and basal blood flow in contralateral carotid. Concentration-response curves for angiotensin II and blood flow were obtained in contralateral carotid from non-treated or capsaicin-treated streptozotocin-induced diabetic rats that underwent to carotid balloon injury. Diabetes increased angiotensin II-induced contraction and impaired the blood flow in non-operated rat carotid. In diabetic rats, balloon injury led to neointima formation, which reduced the blood flow in ipsilateral carotid. Carotid balloon injury in diabetic rats reduced angiotensin II-induced contraction and restored the blood flow in contralateral carotid when compared to diabetic non-operated rat carotid. Capsaicin inhibited the effects evoked by carotid balloon injury on diabetic rat contralateral carotid. Endothelium removal, PEG-catalase (hydrogen peroxide scavenger) or L-NPA (neuronal nitric oxide synthase, nNOS, inhibitor) increased angiotensin II-induced contraction in contralateral carotid from diabetic operated rats to the levels observed in diabetic non-operated rat carotid. Our findings suggest that carotid balloon injury in diabetic rats elicits a neurocompensation that attenuates the diabetic hyperreactivity to angiotensin II in contralateral carotid by a sensory nerves-dependent mechanism mediated by hydrogen peroxide derived from endothelial nNOS. This sensory mechanism also restored the blood flow in this vessel, compensating the impaired blood flow in diabetic rat ipsilateral carotid. Thus, our major conclusions are that Diabetes confers a vasoprotective significance to the neurocompensation to carotid balloon injury in preventing further damage at carotid cerebral irrigation after angioplasty in diabetic subjects.
    European journal of pharmacology 03/2013; · 2.59 Impact Factor
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    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 09/2012; · 1.08 Impact Factor
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    Journal of pediatric gastroenterology and nutrition 02/2012; · 2.18 Impact Factor
  • Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 10/2011; 103(10):551-553. · 1.65 Impact Factor
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    Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 10/2011; 103(10):551-3. · 1.65 Impact Factor
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    ABSTRACT: The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality. Acute lung injury is the hallmark of the disease, but multiple organ system dysfunction can develop and lead to death. Therefore, we sought to investigate whether there was postmortem evidence of H1N1 presence and virus-induced organ injury in autopsy specimens. Five cases in which patients died of influenza A (H1N1) virus infection were studied. The lungs of all patients showed macroscopic and microscopic findings already described for H1N1 (consolidation, edema, hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1 viruses were present in alveolar cells in immunochemical studies. Acute tubular necrosis was present in all cases, but there was no evidence of direct virus-induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide strong evidence that H1N1 presence is not restricted to the lungs.
    American Journal of Clinical Pathology 09/2011; 136(3):416-23. · 2.88 Impact Factor
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    ABSTRACT: We report a 2-year-old child with extrahepatic portal venous obstruction, hepatoportal sclerosis and pulmonary thromboembolism whose sole hypercoagulability factor was the presence of anti-phospholipid antibodies.
    Journal of Tropical Pediatrics 06/2011; 57(3):222-4. · 1.01 Impact Factor
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    ABSTRACT: In this work, Raman spectra in the 900–1,800cm−1 wavenumber region of in vivo and ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured. In the case of the in vivo tissues, the Raman spectra were collected for both transcutaneous (with skin) and skin-removed tissues. To identify the spectral differences between normal and cancer breast tissue, the paired t-test was carried out for each wavenumber using the whole spectral range from both groups. Quadratic discriminate analysis based on principal component analysis (PCA) was also used to determine and evaluate differences in the Raman spectra for the various samples as a basis for diagnostic purposes. The differences in the Raman spectra of the samples were due to biochemical changes at the molecular, cellular and tissue levels. The sensitivity and specificity of the classification scheme based on the differences in the Raman spectra obtained by PCA were evaluated using the receiver operating characteristic (ROC) curve. The in vivo transcutaneous normal and abnormal tissues were correctly classified based on their measured Raman spectra with a discriminant proportion of 73%, while the in vivo skin-removed normal and abnormal tissues were correctly classified again based on their measured Raman spectra with a discriminant proportion of 86%. This result reveals a strong influence due to the skin of the breast, which decreased the specificity by 11%. Finally, the results from ex vivo measurements gave the highest specificity and sensitivity: 96 and 97%, respectively, as well as a largest percentage for correct discrimination: 94%. Now that the important bands have been experimentally determined in this and other works, what remains is for first principles molecular-level simulations to determine whether the changes are simply due to conformational changes, due to aggregation, due to changes in the environment, or complex interactions of all of the above. KeywordsBreast cancer–Raman spectroscopy–Receiver operator characteristic curve–Principal component analysis–Quadratic discriminant analysis–Cancer detection–Cancer diagnostic–Optical biopsy
    Theoretical Chemistry Accounts 01/2011; 130(4):1239-1247. · 2.14 Impact Factor
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    ABSTRACT: Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. CONCLUSION THE: H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits.
    European journal of gastroenterology & hepatology 10/2010; 22(10):1204-10. · 1.66 Impact Factor
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    ABSTRACT: Autoimmune hepatitis is an inflammatory chronic disease of the liver, which frequently results in cirrhosis. The present study aimed to verify the relationship between plasma cells and stellate cells in autoimmune hepatitis. Thirty-three pre-treatment, 11 post-treatment, and 10 normal liver biopsies were reviewed. Sirius Red staining (for semi-quantitative analysis of hepatic fibrosis) and immunohistochemistry were carried out: double staining for smooth muscle α-actin and plasma cell marker (for detection and localization of activated hepatic stellate cells and plasma cells, respectively); and single staining for glial fibrillary acid protein (for detection of hepatic stellate cells). We found an increase in the stellate cell population, mainly with an activated phenotype in autoimmune hepatitis, compared to the control group (liver specimens with no histological evidence of liver disease, obtained from patients undergoing hepatic resection for benign liver mass). A positive significant correlation was observed between stellate cells and scores of fibrosis (measured by Sirius Red) and the number of plasma cells. Additionally, there was a co-localization of plasma cells and activated stellate cells. We also observed a reduction in the number of plasma cells, hepatic stellate cells, and fibrosis in patients who had successfully been treated and had a second liver biopsy post-treatment. Our findings support that the number of plasma cells can be a surrogate marker for the severity of liver disease, reflecting the number of hepatic stellate cells and the amount of fibrosis. It remains to be seen if this is a result of a direct interaction between the plasma cells and hepatic stellate cells or the response to the same stimulus that affects both cellular types.
    Pathology - Research and Practice 10/2010; 206(12):800-4. · 1.21 Impact Factor
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    Geoevents, Geological Heritage, and the Role of IGCP (Marcos A. Lamolda et al., Eds.), Caravaca de La Cruz; 09/2010
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    VIII Congresso Nacional de Geologia, Braga; 07/2010
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    ABSTRACT: Breast cancer is the most frequent cancer type in women Worldwide. Sensitivity and specificity of clinical breast examinations have been estimated from clinical trials to be approximately 54 % and 94 %, respectively. Further, approximately 95 % of all positive breast cancer screenings turn out to be false-positive. The optimal method for early detection should be both highly sensitive to ensure that all cancers are detected, and also highly specific to avoid the humanistic and economic costs associated with false-positive results. In vivo optical spectroscopy techniques, Raman in particular, have been pointed out as promising tools to improve the accuracy of screening mammography. The aim of the present study was to apply FT-Raman spectroscopy to discriminate normal and adenocarcinoma breast tissues of Sprague-Dawley female rats. The study was performed on 32 rats divided in the control (N=5) and experimental (N=27) groups. Histological analysis indicated that mammary hyperplasia, cribriform, papillary and solid adenocarcinomas were found in the experimental group subjects. The spectral collection was made using a commercial FT-Raman Spectrometer (Bruker RFS100) equipped with fiber-optic probe (RamProbe) and the spectral region between 900 and 1800 cm -1 was analyzed. Principal Components Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. As concluding remarks it is show that normal and adenocarcinoma tissues discriminations was possible (correct proportion for Transcutaneous collection mode was 80.80% and for "Open Sky" mode was 91.70%); however, a conclusive diagnosis among the four lesion subtypes was not possible.
    Proc SPIE 02/2010;
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Leandra N Z Ramalho, Carmen C S Martin, Talita Zerbini
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    ABSTRACT: Benign tumors of the esophagus are rare but can lead be fatal when aspirated into the upper airway. Here, we describe a sudden death due to aspiration of a fibrovascular polyp supported by a review of 11 cases from the literature.
    The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 12/2009; 31(1):103-5. · 0.71 Impact Factor
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    ABSTRACT: We aimed to investigate whether hyperhomocysteinemia (HHcy) interferes on carotid vascular reactivity, and how morphological and functional aspects are related. With this purpose male Wistar rats received a solution of dl-homocysteine-thiolactone (1g/kg body weight/day) in the drinking water for 4, 15 and 30 days. Lipid profile, carotid artery-morphology and -responsiveness to acetylcholine, phenylephrine and endothelin-1 were analyzed. Similar increase on homocysteine plasmatic levels occurred in rats treated for 4, 15 and 30 days. High levels of serum cholesterol and triglycerides were observed after HHcy 30 days. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy induced a time-dependent reduction on acetylcholine-induced-relaxation at 4, 15 and 30 days. HHcy enhanced the contractile response of endothelium-intact, but not denuded carotid rings to phenylephrine and endothelin-1, despite the treatment time. Morphometric analysis showed that intimal/medial area ratio was enhanced only at 30 days of HHcy, despite its reduced cell density. The major new finding of the present study is that it establishes a time-course relationship for the events involved on vascular effects associated with HHcy. We demonstrated that alterations on vascular responsiveness precede alterations on arterial structure. Based on such findings it is possible to suggest that vascular dysfunction occurs in early stages while alterations on vessel morphology take place in latest stages of HHcy.
    Vascular Pharmacology 09/2009; 51(4):291-8. · 3.21 Impact Factor
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    ABSTRACT: To investigate the relationship between NF-kappaB activation and hepatic stellate cell (HSC) apoptosis in hepatosplenic schistosomiasis, hepatic biopsies from patients with Schistosoma mansoni-induced periportal fibrosis, hepatitis C virus-induced cirrhosis, and normal liver were submitted to alpha-smooth muscle actin (alpha-SMA) and NF-kappaB p65 immunohistochemistry, as well as to NF-kappaB Southwestern histochemistry and TUNEL assay. The numbers of alpha-SMA-positive cells and NF-kappaB- and NF-kappaB p65-positive HSC nuclei were reduced in schistosomal fibrosis relative to liver cirrhosis. In addition, increased HSC NF-kappaB p65 and TUNEL labeling was observed in schistosomiasis when compared to cirrhosis.These results suggest a possible relationship between the slight activation of the NF-kappaB complex and the increase of apoptotic HSC number in schistosome-induced fibrosis, taking place to a reduced HSC number in schistosomiasis in relation to liver cirrhosis. Therefore, the NF-kappaB pathway may constitute an important down-regulatory mechanism in the pathogenesis of human schistosomiasis mansoni, although further studies are needed to refine the understanding of this process.
    Acta tropica 09/2009; 113(1):66-71. · 2.79 Impact Factor

Publication Stats

492 Citations
107.74 Total Impact Points

Institutions

  • 1993–2011
    • University of São Paulo
      • • Faculdade de Medicina de Ribeirão Preto (FMRP)
      • • Departamento de Patologia (FM) (São Paulo)
      • • Hospital das Clínicas (FMUSP)
      • • Faculty of Medicine (FM)
      São Paulo, Estado de Sao Paulo, Brazil
  • 1994–2010
    • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
      San Paulo, São Paulo, Brazil