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1.
Ecancermedicalscience ; 15: 1246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267802

RESUMO

BACKGROUND: Cancer patients are at higher risk of infection and severity of Coronavirus Disease-19 (COVID-19). Management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging due to the scarce scientific information and treatment guidelines. In this work, we present our Institutional experience with our first 100 patients with oncological malignancies and COVID-19. PATIENTS AND METHODS: We conducted a cross-sectional study of the first 100 patients hospitalised at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru) who were positive for SARS-CoV-2 by reverse transcriptase (RT)-PCR during the period 30 March to 20 June. Clinicopathological variables of the oncological disease as well as risk factors, management and outcomes to COVID-19 were evaluated. RESULTS: The mean age was 43.5 years old (standard deviations: ±24.8) where 57% were male patients. In total, 44%, 37% and 19% were adult patients bearing solid tumours, adults with haematologic malignancies and paediatric patients, respectively. Hypertension was the most frequent comorbidity (23%) followed by chronic lung disease (10%). COVID-19-associated symptoms included cough (65%), fever (57%) and dyspnoea (56%). Twelve percent of patients were asymptomatic. Nosocomial infections were more frequent in paediatric patients (84.2%) than in adult patients (16.0%). Patients with uncontrolled oncological disease were most frequent (72%). Anaemia was present in 67% of patients, 68% had lymphopenia, 62% had ferritin value > 500 mcg/L, 85% had elevated lactate dehydrogenase (LDH), 83% D-dimer > 500 ng/mL and 80% C-Reactive Protein > 8 mg/L. The most common complication was acute respiratory failure (42%). Overall fatality rate was 39% where the main cause of mortality was acute respiratory distress syndrome (64.1%). CONCLUSION: Paediatric patients had better outcomes than adult populations, and a high number of asymptomatic carriers and nosocomial infection, early diagnosis are recommended. Considering oncological treatments 30 days before COVID-19 diagnosis, our data did not reveal an increased mortality.

2.
Front Neurosci ; 8: 47, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24723845

RESUMO

Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified. In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by overexpression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat fetus into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that nicotinamide constitutes a lead for exploring compounds with similar or better pharmacological profiles.

3.
Exp Cell Res ; 319(14): 2196-204, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23756134

RESUMO

All-trans retinoic acid (RA) signals via binding to retinoic acid receptors (RARs α, ß, and γ). RA directly influences expression of Pdx1, a transcription factor essential for pancreatic development and beta-cell (ß-cell) maturation. In this study we follow the differentiation of cultured wild-type (WT) vs. RARß knockout (KO) embryonic stem (ES) cells into pancreatic islet cells. We found that RARß KO ES cells show greatly reduced expression of some important endocrine markers of differentiated islet cells, such as glucagon, islet amyloid polypeptide (Iapp), and insulin 1 (Ins1) relative to WT. We conclude that RARß activity is essential for proper differentiation of ES cells to pancreatic endocrine cells.


Assuntos
Diferenciação Celular/genética , Deleção de Genes , Ilhotas Pancreáticas/citologia , Receptores do Ácido Retinoico/genética , Animais , Linhagem Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Glucagon/genética , Glucagon/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Insulina/genética , Insulina/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores do Ácido Retinoico/metabolismo , Transativadores/genética , Transativadores/metabolismo , Transcrição Gênica , Tretinoína/metabolismo
4.
Neurobiol Dis ; 35(1): 82-90, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19393318

RESUMO

Neutrophil elastase (NE) degrades basal lamina and extracellular matrix molecules, and recruits leukocytes during inflammation; however, a basic understanding of the role of NE in stroke pathology is lacking. We measured an increased number of extravascular NE-positive cells, as well as increased levels of tissue elastase protein and activity, following transient middle cerebral artery occlusion (tMCAo). Both pharmacologic inhibition of NE with ZN200355 (ZN), and genetic deletion of NE, significantly reduced infarct volume, blood-brain barrier disruption, vasogenic edema, and leukocyte-endothelial adherence 24 h after tMCAo. ZN also reduced infarct volume in MMP9-null mice following tMCAo. There were, however, no reductions in infarct volume or vasogenic edema in NE-null mice in two models of permanent middle cerebral artery occlusion. Our findings confirm the involvement of NE in neurovascular stroke pathology, when reperfusion allows neutrophils access to vulnerable brain, with pharmacologic or genetic inhibition of NE being both neuro- and vasculo-protective in this setting.


Assuntos
Infarto Encefálico/etiologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Elastase de Leucócito/deficiência , Elastase de Leucócito/metabolismo , Traumatismo por Reperfusão/patologia , Análise de Variância , Animais , Gasometria , Pressão Sanguínea/genética , Barreira Hematoencefálica/fisiopatologia , Encéfalo/irrigação sanguínea , Edema Encefálico/patologia , Infarto Encefálico/prevenção & controle , Adesão Celular , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Fluxometria por Laser-Doppler/métodos , Elastase de Leucócito/antagonistas & inibidores , Leucócitos/patologia , Masculino , Metaloproteinase 9 da Matriz/deficiência , Camundongos , Camundongos Knockout , Traumatismo por Reperfusão/metabolismo , Sais de Tetrazólio
5.
Rev Panam Salud Publica ; 17(3): 147-53, 2005 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-15826393

RESUMO

OBJECTIVES: To determine the prevalence of antibodies against Trypanosoma cruzi in puerperal women and to assess possible congenital transmission of Chagas' disease in the department of Arequipa, Peru, where the disease is endemic. METHODS: Women who had given birth between December 2001 and July 2002 in three hospitals (two urban and one rural) and four health centers (three rural and one urban) of the department of Arequipa, Peru, were studied. The serological study included screening all the puerperal women in order to detect antibodies against T. cruzi through indirect immunofluorescence (IIF), with confirmatory testing done with enzyme-linked immunosorbent assay (ELISA) testing and the titration of immunoglobulin G (IgG) antibodies by IIF. IIF tests to screen for immunoglobulin M (IgM) antibodies were done with the seropositive women and their newborns, and infection was evaluated through xenodiagnosis (evaluated at 30 and 60 days) and the direct micromethod of Freilij et al. The results were analyzed in terms of the presence of the vector and of cases of Chagas' disease in the places where the puerperal women had been born and where they were living. Two neonatologists clinically evaluated the newborns in order to detect abnormalities and signs of congenital Chagas' disease. RESULTS: The overall prevalence of Chagas' disease in the 3 000 puerperal women studied was 0.73%. Prevalence was highest in two health centers located in rural areas (2.2% in El Pedregal and 4.1% in La Joya) (P=0.018). The disease was associated with previous direct contact with the vector (P<0.05) and with having been born in an area considered endemic (P<0.01). Four (20%) of the 20 seropositive puerperal women were also positive by xenodiagnosis. However, none of the women was aware of her infectious carrier state, and none showed the characteristic symptoms or signs of acute or chronic Chagas' disease. IgM antibodies were not detected in any of the puerperal women. One neonate (whose mother did not have evidence of parasitemia) presented an IgM titer of 1/8, but in later controls neither IgM nor IgG antibodies were detected. Parasites were not detected in the blood of the neonates by either of the two testing methods used. Of the 20 neonates evaluated, one presented microcephaly and hepatosplenomegaly; although the child had specific IgG antibodies against T. cruzi at birth, the antibodies were not present at the age of two months. The growth and development of the other 19 newborns were normal. CONCLUSIONS: The prevalence of Chagas' disease in puerperal women of the department of Arequipa, Peru, is low. No cases of intrauterine congenital transmission were found. We recommend carrying out studies on prenatal detection that evaluate more mothers and in which women who give birth at home also participate.


Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Doenças Endêmicas , Transtornos Puerperais/epidemiologia , Adolescente , Adulto , Doença de Chagas/congênito , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência
6.
Am J Physiol Heart Circ Physiol ; 289(2): H558-68, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15764676

RESUMO

Results of recent studies reveal vascular and neuroprotective effects of matrix metalloproteinase-9 (MMP-9) inhibition and MMP-9 gene deletion in experimental stroke. However, the cellular source of MMP-9 produced in the ischemic brain and the mechanistic basis of MMP-9-mediated brain injury require elucidation. In the present study, we used MMP-9-/- mice and chimeric knockouts lacking either MMP-9 in leukocytes or in resident brain cells to test the hypothesis that MMP-9 released from leukocytes recruited to the brain during postischemic reperfusion contributes to this injury phenotype. We also tested the hypothesis that MMP-9 promotes leukocyte recruitment to the ischemic brain and thus is proinflammatory. The extent of blood-brain barrier (BBB) breakdown, the neurological deficit, and the volume of infarction resulting from transient focal stroke were abrogated to a similar extent in MMP-9-/- mice and in chimeras lacking leukocytic MMP-9 but not in chimeras with MMP-9-containing leukocytes. Zymography and Western blot analysis from these chimeras confirmed that the elevated MMP-9 expression in the brain at 24 h of reperfusion is derived largely from leukocytes. MMP-9-/- mice exhibited a reduction in leukocyte-endothelial adherence and a reduction in the number of neutrophils plugging capillaries and infiltrating the ischemic brain during reperfusion; microvessel immunopositivity for collagen IV was also preserved in these animals. These latter results document proinflammatory actions of MMP-9 in the ischemic brain. Overall, our findings implicate leukocytes, most likely neutrophils, as a key cellular source of MMP-9, which, in turn, promotes leukocyte recruitment, causes BBB breakdown secondary to microvascular basal lamina proteolysis, and ultimately contributes to neuronal injury after transient focal stroke.


Assuntos
Barreira Hematoencefálica , Mediadores da Inflamação/metabolismo , Ataque Isquêmico Transitório/metabolismo , Leucócitos/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Animais , Contagem de Células Sanguíneas , Vasos Sanguíneos/patologia , Western Blotting , Adesão Celular , Infarto Cerebral/patologia , Circulação Cerebrovascular , Colágeno Tipo IV/metabolismo , Endotélio Vascular/patologia , Hemodinâmica , Ataque Isquêmico Transitório/enzimologia , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Doenças do Sistema Nervoso/prevenção & controle , Infiltração de Neutrófilos
10.
Sucre; s.n; 2002. 128 p. ilus, graf.
Tese em Espanhol | LILACS-Express | LIBOCS, LIBOSP | ID: biblio-1326148
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