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Hospital Universitário Antônio Pedro

Hospital / health systemNiterói, Brazil

Research output, citation impact, and the most-cited recent papers from Hospital Universitário Antônio Pedro (Brazil). Aggregated across the NobleBlocks index of 300M+ scholarly works.

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1.7K
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35.2K
h-index
72
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1.0K
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Hospital Universitário Antônio Pedro

Top-cited papers from Hospital Universitário Antônio Pedro

Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity
Fernando A. Bozza, Oswaldo G. Cruz, Sonia MO Zagne, Elzinandes Leal de Azeredo +4 more
2008· BMC Infectious Diseases363doi:10.1186/1471-2334-8-86

BACKGROUND: Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity. METHODS: Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis. RESULTS: IL-1beta, IFN-gamma, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1beta levels were observed in patients with mild dengue. MIP-1beta was also associated with CD56+NK cell circulating rates. IL-1beta, IL-8, TNF-alpha and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1beta and IFN-gamma were independently associated with both dengue severity and disease outcome. CONCLUSION: Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-beta is indicated for the first time as a good prognostic marker in contrast to IFN-gamma that was associated with disease severity.

A NEW TECHNIQUE FOR REDUCTION MAMMAPLASTY
Liacyr Ribeiro
1975· Plastic & Reconstructive Surgery298doi:10.1097/00006534-197555030-00010

Rio de Janeiro, Brazil From the Hospital Universitãrio Antõnio Pedro, Faculdade de Medicina, Universidade Federal Fluminense. Presented at the Annual Meeting of the Brazilian Society of Plastic Surgery on May 9, 1974, in Belo Horizonte, Brazil.

Gas physics, disk fragmentation, and bulge formation in young galaxies
A. Immeli, M. Samland, O. Gerhard, P. Westera
2003· Astronomy and Astrophysics259doi:10.1051/0004-6361:20034282

We investigate the evolution of star-forming gas-rich disks, using a 3D chemodynamical model including a dark halo, stars, and a two-phase interstellar medium with feedback processes from the stars. We show that galaxy evolution proceeds along very different routes depending on whether it is the gas disk or the stellar disk which first becomes unstable, as measured by the respective Q-parameters. This in turn depends on the uncertain efficiency of energy dissipation of the cold cloud component from which stars form. When the cold gas cools efficiently and drives the instability, the galactic disk fragments and forms a number of massive clumps of stars and gas. The clumps spiral to the center of the galaxy in a few dynamical times and merge there to form a central bulge component in a strong starburst. When the kinetic energy of the cold clouds is dissipated at a lower rate, stars form from the gas in a more quiescent mode, and an instability only sets in at later times, when the surface density of the stellar disk has grown sufficiently high. The system then forms a stellar bar, which channels gas into the center, evolves, and forms a bulge whose stars are the result of a more extended star formation history. We investigate the stability of the gas-stellar disks in both regimes, as well as the star formation rates and element enrichment. We study the morphology of the evolving disks, calculating spatially resolved colours from the distribution of stars in age and metallicity, including dust absorption. We then discuss morphological observations such as clumpy structures and chain galaxies at high redshift as possible signatures of fragmenting, gas-rich disks. Finally, we investigate abundance ratio distributions as a means to distinguish the different scenarios of bulge formation.

A NEW TECHNIQUE FOR REDUCTION MAMMAPLASTY
Liacyr Ribeiro
1975· Plastic & Reconstructive Surgery242doi:10.1097/00006534-197503000-00010

We present a new technique of reduction mammaplasty which we have employed in 20 cases. We believe it has specific advantages, as outlined.

COVID-19: clinical and laboratory manifestations in novel coronavirus infection
Analúcia Rampazzo Xavier, Jonadab dos Santos Silva, João Paulo Chevrand Latini de Almeida, Johnatan Felipe Ferreira da Conceição +2 more
2020· Jornal Brasileiro de Patologia e Medicina Laboratorial195doi:10.5935/1676-2444.20200049

ABSTRACT COVID-19 is a highly contagious disease caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2). In 2020, due to the outbreak, it was considered by the World Health Organization (WHO) as a pandemic. The infection caused by the novel coronavirus has high mortality in a small portion of the infected population, especially in elderly, immunosuppressed, diabetic, cardiac, and hypertensive individuals. Many infected are asymptomatic (and may be carriers) or present mild or moderate flu-like symptoms. The most severe clinical picture of COVID-19 is characterized by an inflammatory cytokine storm, with hematological changes and coagulation dysfunction, which can lead to tissue damage and death. Nonspecific laboratory biomarkers may be either increased or decreased as the course of the disease progresses and are often useful in predicting complications of the disease, such as the use of D-dimer and platelet/lymphocyte ratio. Specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) by real-time polymerase chain reaction (RT-PCR) of nasal and oropharyngeal swab samples; it is more effective when performed in the first days after symptom onset. Serological tests are useful in detecting the immune response, since both class M (IgM) and class G (IgG) immunoglobulin antibodies can be detected seven days after the onset of clinical symptoms, and may extend for more than 25 days, although not exempting the individual from remaining infectious, depending on their viral load and clinical presentation. The rational use of specific laboratory markers must respect the disease chronology, and the correct interpretation may provide subsidies for a better management of affected patients, as well as identifying asymptomatic carriers or those with mild symptoms.

Risk Factors for Death in Patients With Candidemia
Márcio Nucci, Arnaldo Lopes Colombo, Fernanda Silveira, Rosana Richtmann +3 more
1998· Infection Control and Hospital Epidemiology167doi:10.1086/647743

OBJECTIVE: To analyze possible risk factors for death among patients with nosocomial candidemia. To identify risk factors for death in patients with candidemia, we analyzed demographic, clinical, and microbiological data. SETTING: Six tertiary hospitals in Brazil. PATIENTS: A cohort of 145 patients with candidemia. DESIGN: 26 possible risk factors for death, including age, underlying disease, signs of deep-seated infection, neutropenia, number of positive blood cultures, removal of a central venous catheter, etiologic agent of the candidemia, susceptibility pattern of the isolate to amphotericin B, and antifungal treatment were evaluated by univariate stepwise logistic regression analysis. RESULTS: Non-albicans species accounted for 63.4% of the candidemias. Risk factors for death in univariate analysis were older age, catheter retention, poor performance status, candidemia due to species other than Candida parapsilosis, hypotension, candidemia due to species other than Candida parapsilosis, and no antifungal treatment. In multivariate analysis, older age and nonremoval of a central venous catheter were the only factors associated with an increased risk for death. CONCLUSIONS: These data suggest that patients with candidemia and a central venous catheter should have the catheter removed.

Gas Physics, Disk Fragmentation, and Bulge Formation in Young Galaxies
Andreas Immeli, M. Samland, Ortwin Gerhard, P. Westera
2003· Springer Link (Chiba Institute of Technology)152doi:10.1051/0004-6361:20034282/pdf

We investigate the evolution of star-forming gas-rich disks, using a 3D chemodynamical model including a dark halo, stars, and a two-phase interstellar medium with feedback processes from the stars. We show that galaxy evolution proceeds along very different routes depending on whether it is the gas disk or the stellar disk which first becomes unstable, as measured by the respective Q-parameters. This in turn depends on the uncertain efficiency of energy dissipation of the cold cloud component from which stars form. When the cold gas cools efficiently and drives the instability, the galactic disk fragments and forms a number of massive clumps of stars and gas. The clumps spiral to the center of the galaxy in a few dynamical times and merge there to form a central bulge component in a strong starburst. When the kinetic energy of the cold clouds is dissipated at a lower rate, stars form from the gas in a more quiescent mode, and an instability only sets in at later times, when the surface density of the stellar disk has grown sufficiently high. The system then forms a stellar bar, which channels gas into the center, evolves, and forms a bulge whose stars are the result of a more extended star formation history. We investigate the stability of the gas-stellar disks in both regimes, as well as the star formation rates and element enrichment. We study the morphology of the evolving disks, calculating spatially resolved colours from the distribution of stars in age and metallicity, including dust absorption. We then discuss morphological observations such as clumpy structures and chain galaxies at high redshift as possible signatures of fragmenting, gas-rich disks. Finally, we investigate abundance ratio distributions as a means to distinguish the different scenarios for bulge formation.

NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease
Elzinandes Leal de Azeredo, Luzia Maria de Oliveira Pinto, Sônia Maria Oliveira Zagne, Denise Cerqueira +2 more
2005· Clinical & Experimental Immunology137doi:10.1111/j.1365-2249.2006.02996.x

During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.

Important prognostic factors for survival in patients with malignant pleural effusion
Mauro Zamboni, Cyro Teixeira da Silva, Rodrigo Baretta, Edson Toscano Cunha +1 more
2015· BMC Pulmonary Medicine136doi:10.1186/s12890-015-0025-z

BACKGROUND: The approach to palliative treatment of malignant pleural effusion (MPE) should be individualized because these patients generally have poor survival. Our study aimed to develop a model to identify prognostic factors or survival time in patients diagnosed with MPE. METHODS: This is a retrospective, descriptive, observational study to identify prognostic factors related to MPE in patients with a confirmed cancer diagnosis. Cox regression analysis was used to determine significant potential prognostic factors with respect to survival time. Survival time was defined as the time from pathological diagnosis to death. RESULTS: One hundred and sixty-five patients were included; 77 were men (47%) and 88 were women (53%). The median age was 60 years, and all of the patients were pathologically proven to have MPE. Non-small-cell lung cancer (36.0%), breast carcinoma (26%), and lymphoma (13.0%) were the most frequently diagnosed tumors. The median overall survival of patients from the initial diagnosis was 5 months (range: 1.0-96.0 months). Kaplan-Meier univariate analysis showed that survival was significantly related to the following prognostic factors: ECOG PS (hazard ratio [HR] 10.0, 95% confidence interval [95% CI] 5.96 to 18.50, p < 0.0001), primary cancer site (HR 1.99, 95% CI 1.23 to 3.22, p < 0.01), positive pleural cytology (HR 1.25, 95% CI 0.88 to 1.78, p = 0.04), and positive histology (HR 1.33, 95% CI 0.97 to 1.81, p = 0.04). Other potential independent diagnostic factors that were examined did not affect survival. Cox regression analysis showed that only the ECOG PS was highly predictive of survival (HR 73.58, 95% CI 23.44 to 230.95, p < 0.0001). CONCLUSIONS: ECOG PS is an independent predictor of survival in patients with MPE at initial diagnosis. This prognostic factor can help physicians select patients for appropriate palliative treatment of this syndrome.

Subgalactic Clumps at High Redshift: A Fragmentation Origin?
Andreas Immeli, Markus Samland, Pieter Westera, Ortwin Gerhard
2004· The Astrophysical Journal132doi:10.1086/422179

We investigate the origin of the clumpy structures observed at high redshift, like the chain galaxies. We use a three dimensional chemodynamical simulation describing the dynamics of stars and a two-phase interstellar medium, as well as feedback processes from the stars. For high efficiency of energy dissipation in the cold cloud medium, the initially gaseous disk fragments and develops several massive clumps of gas and stars. We follow the evolution of the individual clumps and determine their masses, metallicities and velocities. A few dynamical times after fragmentation of the disk, the clumps merge to build a massive bulge. Calculating HST- and UBVRIJHKLM-colors, including absorption by interstellar dust, we determine the morphologies and colors of this model in HST images. Several peculiar morphological structures seen in the HDF can be well-explained by a fragmented galactic disk model, including chain galaxies and objects consisting of several nearby knots.

Diffusion Tensor Imaging Findings in School‐Aged Autistic Children
Adriana Rocha Brito, Marcio Moacyr Vasconcelos, Romeu Côrtes Domingues, Luiz Celso Hygino da Cruz +3 more
2009· Journal of Neuroimaging115doi:10.1111/j.1552-6569.2009.00366.x

OBJECTIVE: To analyze and compare cerebral white matter tracts through diffusion tensor imaging in autistic and normal children. METHODS: This is a case-control study on a sample of eight male, right-handed children diagnosed with autism according to Diagnostic and Statistical Manual of Mental Disorders-4th Edition criteria, and eight healthy age- and sex-matched controls. Imaging studies were performed on a 1.5-T scanner (Symphony Maestro Class, Siemens, Erlangen, Germany). Fractional anisotropy was calculated for the frontopontine and corticospinal tracts, frontal subcortical white matter, anterior cingulate, corpus callosum, striatum, internal capsule, optic radiation, superior and inferior longitudinal fascicles, and cerebellum. Analysis of significance was based on analysis of variance test for the mean fractional anisotropy values. RESULTS: Median age of cases was 9.53 +/- 1.83 years, and of controls, 9.57 +/- 1.36 years. Diffusion tensor imaging findings included significant reduction of fractional anisotropy in the anterior corpus callosum (P= .008), right corticospinal tract (P= .044), posterior limb of right and left internal capsules (P= .003 and .049, respectively), left superior cerebellar peduncle (P= .031), and right and left middle cerebellar peduncles (P= .043 and .039, respectively) in autistic children. CONCLUSIONS: The diffusion tensor imaging findings in children with autistic disorder suggest impairment of white matter microstructure, possibly associated with reduced connectivity in corpus callosum, internal capsule, and superior and middle cerebellar peduncles.

Carbapenem-hydrolysing  -lactamase KPC-2 in Klebsiella pneumoniae isolated in Rio de Janeiro, Brazil
Gisele Peirano, Liliane Miyuki Seki, V. L. Val Passos, Margarida Pinto +2 more
2008· Journal of Antimicrobial Chemotherapy108doi:10.1093/jac/dkn484

OBJECTIVES: The aim of this study was to characterize the KPC-type carbapenem-hydrolysing beta-lactamase, extended-spectrum beta-lactamases (ESBLs) and class 1 integrons among nosocomial Klebsiella pneumoniae isolated in Rio de Janeiro, Brazil. METHODS: MICs were determined and isolates were screened for ESBLs, metallo-beta-lactamases (MBLs) and class A carbapenemase-producing phenotypes. The main beta-lactamases resistance genes (bla(TEM), bla(SHV), bla(CTX-M), bla(KPC), bla(IMP) and bla(VIM)) and class 1 integrons were detected by PCR followed by DNA sequencing. The genetic relatedness of isolates was determined by PFGE. RESULTS: All K. pneumoniae isolates were positive for ESBL and class A carbapenemase production and negative for MBL production. All isolates were resistant to all beta-lactam antibiotics, ciprofloxacin and gentamicin, being susceptible only to tigecycline and polymyxin B. The bla(KPC-2), bla(CTX-M-1), bla(CTX-M-2), bla(CTX-M-8) and bla(SHV-11) genes were detected. PFGE analysis revealed two clonal types among KPC-producing isolates, both identified in the same hospital. CONCLUSIONS: Our findings should alert medical authorities to implement stringent methods for the detection and spread control of emerging KPC-2 carbapenemases in the hospital setting in Brazil.

Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection
Patrícia CF Neves-Souza, Elzinandes Leal de Azeredo, Sonia MO Zagne, Rogério Valls-de-Souza +4 more
2005· BMC Infectious Diseases106doi:10.1186/1471-2334-5-64

UNLABELLED: Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV) replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-alpha, which has also been detected in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities. METHODS: The expression of DENV antigens and inducible nitric oxide synthase (iNOS) in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis. RESULTS: INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days), significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells. CONCLUSION: This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production.

Differential regulation of toll‐like receptor‐2, toll‐like receptor‐4, CD16 and human leucocyte antigen‐DR on peripheral blood monocytes during mild and severe dengue fever
Elzinandes Leal de Azeredo, Patrícia CF Neves-Souza, Allan R. Alvarenga, Sônia R. N. I. Reis +4 more
2010· Immunology105doi:10.1111/j.1365-2567.2009.03224.x

Dengue fever (DF), a public health problem in tropical countries, may present severe clinical manifestations as result of increased vascular permeability and coagulation disorders. Dengue virus (DENV), detected in peripheral monocytes during acute disease and in in vitro infection, leads to cytokine production, indicating that virus-target cell interactions are relevant to pathogenesis. Here we investigated the in vitro and in vivo activation of human peripheral monocytes after DENV infection. The numbers of CD14(+) monocytes expressing the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) were significantly increased during acute DF. A reduced number of CD14(+) human leucocyte antigen (HLA)-DR(+) monocytes was observed in patients with severe dengue when compared to those with mild dengue and controls; CD14(+) monocytes expressing toll-like receptor (TLR)2 and TLR4 were increased in peripheral blood from dengue patients with mild disease, but in vitro DENV-2 infection up-regulated only TLR2. Increased numbers of CD14(+) CD16(+) activated monocytes were found after in vitro and in vivo DENV-2 infection. The CD14(high) CD16(+) monocyte subset was significantly expanded in mild dengue, but not in severe dengue. Increased plasma levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-18 in dengue patients were inversely associated with CD14(high) CD16(+), indicating that these cells might be involved in controlling exacerbated inflammatory responses, probably by IL-10 production. We showed here, for the first time, phenotypic changes on peripheral monocytes that were characteristic of cell activation. A sequential monocyte-activation model is proposed in which DENV infection triggers TLR2/4 expression and inflammatory cytokine production, leading eventually to haemorrhagic manifestations, thrombocytopenia, coagulation disorders, plasmatic leakage and shock development, but may also produce factors that act in order to control both intense immunoactivation and virus replication.

A multiparametric assay to compare the cytotoxicity of endodontic sealers with primary human osteoblasts
Míriam Zaccaro Scelza, Adriana Linhares, Licínio Esmeraldo da Silva, José Mauro Granjeiro +1 more
2011· International Endodontic Journal96doi:10.1111/j.1365-2591.2011.01941.x

AIM: To compare the cytotoxicity of four endodontic sealers (Sealapex, Pulp Canal Sealer EWT, Real Seal and MTA Fillapex) either 1 or 7 days after mixing, when assessed through a multiparametric analysis employing human primary cells closely related to periapical tissues. METHODOLOGY: Extracts of each sealer were prepared following 24-h exposure to culture media, at either 24 h or 7 days after mixing. Primary human osteoblasts were exposed to extracts for 24 h, at 37 °C with 5% CO(2) , and cell viability was evaluated by a multiparametric assay assessing sequentially, on the same cells, mitochondrial activity (XTT), membrane integrity (neutral red test) and total cell density (crystal violet dye exclusion test). Results from each test and experimental time were compared by 2-way analysis of variance (anova). RESULTS: All endodontic sealers had strong cytotoxicity 24 h after mixing, according to all parameters evaluated. At a longer setting period (7 days), viability for Sealapex was significantly increased (P < 0.05) and Pulp Canal Sealer achieved levels of cytocompatibility similar to the control group. The anova indicated a general correlation between the cytotoxicity of the materials and the time after mixing, with some level of dependence on the cell viability assay employed. CONCLUSIONS: All materials had high cytotoxic levels for human primary cells, mostly on a time-dependent basis, as shown by three different cell viability tests.

Cytocompatibility of the ready‐to‐use bioceramic putty repair cement iRoot BP Plus with primary human osteoblasts
Gustavo De‐Deus, Antônio Canabarro, Gutemberg Gomes Alves, Juliana Marins +2 more
2012· International Endodontic Journal95doi:10.1111/j.1365-2591.2011.02003.x

AIM: To verify the in vitro cytocompatibility of iRoot BP Plus (iRoot) and to compare it with White ProRoot MTA (MTA). METHODOLOGY: Thirty-six human maxillary incisor root canals were prepared using a step-back flaring technique. The apical 3 mm was resected perpendicular to the long axis at the roots, and root-end cavities were prepared with the aid of an ultrasonic device plus a diamond retrotip with continuous irrigation using water, producing standardized preparations. After that, the root-end cavities were filled with iRoot or MTA, and each root was exposed to cell culture media for 24 or 48 h. Human osteoblast cells were exposed to the extracts thus obtained, and a multiparametric cell viability assay was performed, evaluating mitochondrial activity, membrane integrity and cell density. The results were analysed by one-way analysis of variance, complemented with the Duncan post-test (P < 0.05). RESULTS: Cells exposed to MTA revealed a cytocompatibility pattern similar to the untreated cells (negative control), at both experimental times (P > 0.05). iRoot, however, promoted a significantly poorer viability than MTA and the control, after 48 h of exposure (P < 0.001). Nevertheless, iRoot did not induce critical cytotoxic effects because cell viability remained higher than 70% of the control group in most tests performed. CONCLUSION: iRoot and MTA were biocompatible and did not induce critical cytotoxic effects.

Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?
Juliana F. Saldanha, Viviane de Oliveira Leal, Peter Stenvinkel, José Carlos Carraro-Eduardo +1 more
2013· Oxidative Medicine and Cellular Longevity92doi:10.1155/2013/963217

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promote transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

Sepsis-Associated Outcomes in Critically Ill Patients with Malignancies
Viviane BL Torres, Luciano C. P. Azevedo, Ulysses V. A. Silva, Pedro Caruso +4 more
2015· Annals of the American Thoracic Society91doi:10.1513/annalsats.201501-046oc

RATIONALE: Sepsis is a major cause of mortality among critically ill patients with cancer. Information about clinical outcomes and factors associated with increased risk of death in these patients is necessary to help physicians recognize those patients who are most likely to benefit from ICU therapy and identify possible targets for intervention. OBJECTIVES: In this study, we evaluated cancer patients with sepsis chosen from a multicenter prospective study to characterize their clinical characteristics and to identify independent risk factors associated with hospital mortality. METHODS: Subgroup analysis of a multicenter prospective cohort study conducted in 28 Brazilian intensive care units (ICUs) to evaluate adult cancer patients with severe sepsis and septic shock. We used logistic regression to identify variables associated with hospital mortality. MEASUREMENTS AND MAIN RESULTS: Of the 717 patients admitted to the participating ICUs, 268 (37%) had severe sepsis (n = 142, 53%) or septic shock (n = 126, 47%). These patients comprised the population of the present study. The mean score on the third version of the Simplified Acute Physiology Score was 62.9 ± 17.7 points, and the median Sequential Organ Failure Assessment score was 9 (7-12) points. The most frequent sites of infection were the lungs (48%), intraabdominal region (25%), bloodstream as primary infection (19%), and urinary tract (17%). Half of the patients had microbiologically proven infections, and Gram-negative bacteria were the most common pathogens causing sepsis (31%). ICU and hospital mortality rates were 42% and 56%, respectively. In multivariable analysis, the number of acute organ dysfunctions (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87), hematological malignancies (OR, 2.57; 95% CI, 1.05-6.27), performance status 2-4 (OR, 2.53; 95% CI, 1.44-4.43), and polymicrobial infections (OR, 3.74; 95% CI, 1.52-9.21) were associated with hospital mortality. CONCLUSIONS: Sepsis is a common cause of critical illness in patients with cancer and remains associated with high mortality. Variables related to underlying malignancy, sepsis severity, and characteristics of infection are associated with a grim prognosis.

Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension
Márcio Galindo Kiuchi, George Luiz Marques Maia, Maria Angela Magalhães de Queiroz Carreira, Tetsuaki Kiuchi +4 more
2013· European Heart Journal87doi:10.1093/eurheartj/eht200

AIMS: Evaluation of the safety and efficacy of renal denervation with a standard irrigated cardiac ablation catheter (SICAC) in chronic kidney disease (CKD) patients with refractory hypertension. METHODS AND RESULTS: Twenty-four patients were included and treated with a SICAC. Denervation was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n = 16), 3 (n = 4), and 4 (n = 4). Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure (mean ± SD) were 186 ± 19 mmHg/108 ± 13 mmHg in the office, and 151 ± 18 mmHg/92 ± 11 mmHg by 24 h ambulatory blood pressure monitoring (ABPM). Office blood pressure values at 180th day after the procedure were 135 ± 13 mmHg/88 ± 7 mmHg (P < 0.0001, for both comparisons). The mean ABPM decreased to 132 ± 15 mmHg/85 ± 11 mmHg at the 180th day after the procedure (P < 0.0001 for systolic and P = 0.0015 for diastolic). Estimated glomerular filtration (mean ± SD) increased from baseline (64.4 ± 23.9 mL/min/1.73 m(2)) to the 180th day (85.4 ± 34.9 mL/min/1.73 m(2), P < 0.0001) of follow-up. The median urine albumin:creatinine ratio decreased from baseline (48.5, IQR: 35.8-157.2 mg/g) to the 180th day after ablation (ACR = 15.7, IQR: 10.3-34.2 mg/g, P = 0.0017). No major complications were seen. CONCLUSION: The procedure using SICAC seemed to be feasible, effective, and safe resulting in a better control of BP, a short-term increase in estimated glomerular filtration rate, and reduced albuminuria. Although encouraging, our data are preliminary and need to be validated in the long term.

Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development
Thomas C. Chen, Clóvis Orlando da Fonseca, Axel H. Schönthal
2018· International Journal of Molecular Sciences83doi:10.3390/ijms19123905

Intracranial malignancies, such as primary brain cancers and brain-localized metastases derived from peripheral cancers, are particularly difficult to treat with therapeutic agents, because the blood-brain barrier (BBB) effectively minimizes brain entry of the vast majority of agents arriving from the systemic circulation. Intranasal administration of cancer drugs has the potential to reach the brain via direct nose-to-brain transport, thereby circumventing the obstacle posed by the BBB. However, in the field of cancer therapy, there is a paucity of studies reporting positive results with this type of approach. A remarkable exception is the natural compound perillyl alcohol (POH). Its potent anticancer activity was convincingly established in preclinical studies, but it nonetheless failed in subsequent clinical trials, where it was given orally and displayed hard-to-tolerate gastrointestinal side effects. Intriguingly, when switched to intranasal delivery, POH yielded highly promising activity in recurrent glioma patients and was well tolerated. As of 2018, POH is the only intranasally delivered compound in the field of cancer therapy (outside of cancer pain) that has advanced to active clinical trials. In the following, we will introduce this compound, summarize its molecular mechanisms of action, and present the latest data on its clinical evaluation as an intranasally administered agent for glioma.