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1.
Exp Cell Res ; 433(2): 113852, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37951335

RESUMEN

In the study of tumorigenesis, the involvement of molecules within the extracellular matrix (ECM) is crucial. ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin motifs), a group of secreted proteases known for their role in ECM remodeling, were primarily considered to be extracellular proteases. However, our research specifically detected ADAMTS-1, a member of this family, predominantly within the nucleus of mammary cells. Our main objective was to understand the mechanism of ADAMTS-1 translocation to the nucleus and its functional significance in this cellular compartment. Our investigation uncovered that nuclear ADAMTS-1 was present in cells exhibiting an epithelial phenotype, while cells of mesenchymal origin contained the protease in the cytoplasm. Moreover, disruption of ADAMTS-1 secretion, induced by Monensin treatment, resulted in its accumulation in the cytoplasm. Notably, our research indicated that alterations in the secretory pathways could influence the protease's compartmentalization. Additionally, experiments with conditioned medium from cells containing nuclear ADAMTS-1 demonstrated its internalization into the nucleus by HT-1080 cells and fibroblasts. Furthermore, heightened levels of ADAMTS-1 within the ECM reduced the migratory potential of mesenchymal cells. This highlights the potential significance of nuclear ADAMTS-1 as a critical component within the tumor microenvironment due to its functional activity in this specific cellular compartment.


Asunto(s)
Proteína ADAMTS1 , Movimiento Celular , Núcleo Celular , Matriz Extracelular , Trombospondinas , Humanos , Proteína ADAMTS1/genética , Proteína ADAMTS1/metabolismo , Carcinogénesis/metabolismo , Endopeptidasas/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Trombospondinas/metabolismo , Microambiente Tumoral , Núcleo Celular/metabolismo
2.
Rev Soc Bras Med Trop ; 56: e0238-2023, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37531520

RESUMEN

BACKGROUND: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. METHODS: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. RESULTS: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. CONCLUSIONS: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Brasil , Sensibilidad y Especificidad , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Genotipo , Costos y Análisis de Costo , Antituberculosos/uso terapéutico
3.
Diagnostics (Basel) ; 13(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37189545

RESUMEN

Zika virus (ZIKV) diagnosis is currently performed through an invasive, painful, and costly procedure using molecular biology. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for ZIKV diagnosis is of great relevance. It is critical to prepare a global strategy for the next ZIKV outbreak given its devastating consequences, particularly in pregnant women. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has been used to discriminate systemic diseases using saliva; however, the salivary diagnostic application in viral diseases is unknown. To test this hypothesis, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with ZIKV (50 µL,105 FFU, n = 7) or vehicle (50 µL, n = 8). Saliva samples were collected on day three (due to the peak of viremia) and the spleen was also harvested. Changes in the salivary spectral profile were analyzed by Student's t test (p < 0.05), multivariate analysis, and the diagnostic capacity by ROC curve. ZIKV infection was confirmed by real-time PCR of the spleen sample. The infrared spectroscopy coupled with univariate analysis suggested the vibrational mode at 1547 cm-1 as a potential candidate to discriminate ZIKV and control salivary samples. Three PCs explained 93.2% of the cumulative variance in PCA analysis and the spectrochemical analysis with LDA achieved an accuracy of 93.3%, with a specificity of 87.5% and sensitivity of 100%. The LDA-SVM analysis showed 100% discrimination between both classes. Our results suggest that ATR-FTIR applied to saliva might have high accuracy in ZIKV diagnosis with potential as a non-invasive and cost-effective diagnostic tool.

4.
Rev. Soc. Bras. Med. Trop ; 56: e0238, 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1449347

RESUMEN

ABSTRACT Background: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. Methods: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. Results: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. Conclusions: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.

5.
Int J Dent ; 2022: 5235376, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338393

RESUMEN

Background: Ameloblastoma is a benign but locally invasive odontogenic epithelial tumor, associated with a high recurrence rate after treatment. The action of enzymes of the metalloproteinase family is important to the degraded extracellular matrix, contributing to invasion. Thus, this study aimed to investigate the gene and protein expression of ADAMTS-1 and versican in ameloblastoma. Materials and Methods: Twenty cases of ameloblastoma (n = 20) and ten dental follicles (DF) (n = 10) were used as a source for immunochemistry and quantitative RT-PCR for determining the protein and mRNA expressions of the concerned genes, respectively. Moreover, western blot and indirect immunofluorescence analysis were performed in AME cells. Results: ADAMTS-1 and versican were overexpressed in DF than ameloblastoma by RT-PCR. However, in the immunolocalization analysis, ADAMTS-1 was expressed in ameloblastoma more than in DF and versican immunostaining obtained a similar pattern between ameloblastoma and DF. Indirect immunofluorescence detected the ADAMTS-1 and versican expression in cell lines derived from ameloblastoma. Western blot from cell lysate and conditioned medium detected ADAMTS-1 bands representing full-length and different processed forms. Monensin treatment confined ADAMTS-1 in the cell cytoplasm. Versican fragments also were detected in different compartments, intracellular and conditioned medium, allowing the versican process by ADAMTS-1. Conclusion: This study showed a distinct expression of ADAMTS-1 and versican in ameloblastoma and DF, with ADAMTS-1 protein higher expression observed in ameloblastoma and possibly cleaved versican. These findings suggested that ADAMTS-1 may participate in tumor invasion, especially for the degradation of substrates (versican) in the ECM.

6.
Int J Mycobacteriol ; 10(2): 136-141, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34558464

RESUMEN

Background: In last years, few attention has given to the patient's prediagnostic costs when evaluating the introduction of new technologies for tuberculosis (TB) and in this context, this study evaluated patient's costs and cost-effectiveness incurred with TB diagnosis comparing BactecTMMGITTM960 system (MGIT) to the Löwestein-Jensen (LJ) culture in a health center and in a university hospital, in Rio de Janeiro City, Brazil. Methods: Patient's mean costs were evaluated during the diagnosis process and cost-effectiveness based on mean time in days for the adoption of appropriate clinical anti-TB treatment in two health units comparing culture by means LJ and MGIT. Results: The mean cost of LJ and MGIT in the health center was U. S. dollars (US$) 26.6 and US$ 45.13, respectively, and in university hospital was US$ 206.87 and US$ 285.48, respectively. Comparing the two approaches for TB diagnosis incurred by the patients, the incremental cost-effectiveness of MGIT compared to LJ was US$ 0.88 and US$ 4.03 per patient, respectively, to reduce the average time to adopt appropriate treatment. Conclusions: The culture method directly impacts patient costs while waiting for the correct diagnosis and contributing to aggravating costs with patients with TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Técnicas Bacteriológicas , Brasil , Análisis Costo-Beneficio , Humanos , Salud Pública , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico
7.
Rev Soc Bras Med Trop ; 54: e07552020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33605382

RESUMEN

INTRODUCTION: The intensification of research and innovation with the creation of networks of rapid and effective molecular tests as strategies for the end of tuberculosis are essential to avoid late diagnosis and for the eradication of the disease. We aimed to evaluate the cost-effectiveness of Xpert®MTB/RIF (Xpert) in the diagnosis of drug-resistant tuberculosis in reference units, in scenarios with and without subsidies, and the respective cost adjustment for today. METHODS: The analyses were performed considering as criterion of effectiveness, negative culture or clinical improvement in the sixth month of follow-up. The comparison was performed using two diagnostic strategies for the drug susceptibility test (DST), BactecTMMGITTM960 System, versus Xpert. The cost effectiveness and incremental cost-effectiveness ratio (ICER) were calculated and dollar-corrected for American inflation (US$ 1.00 = R$ 5,29). RESULTS: Subsidized Xpert had the lowest cost of US$ 33.48 (R$67,52) and the highest incremental average efficiency (13.57), thus being a dominated analysis. After the inflation was calculated, the mean cost was DST-MGIT=US$ 74.85 (R$ 396,73) and Xpert = US$ 37.33 (R$197,86) with subsidies. CONCLUSIONS: The Xpert in the diagnosis of TB-DR in these reference units was cost-effective with subsidies. In the absence of a subsidy, Xpert in TB-DR is not characterized as cost effective. This factor reveals the vulnerability of countries dependent on international organizations' subsidy policies.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Análisis Costo-Beneficio , Humanos , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico
8.
Cell Signal ; 77: 109827, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33161094

RESUMEN

ADAMTSs (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) are secreted proteases dependent on Zn2+/Ca2+, involved in physiological and pathological processes and are part of the extracellular matrix (ECM). Here, we investigated if ADAMTS-1 is required for invasion and migration of cells and the possible mechanism involved. In order to test ADAMTS-1's role in ovarian cancer cells (CHO, NIH-OVCAR-3 and ES2) and NIH-3 T3 fibroblasts, we modified the levels of ADAMTS-1 and compared those to parental. Cells exposed to ADAMTS-1-enriched medium exhibited a decline in cell migration and invasion when compared to controls with or without a functional metalloproteinase domain. The opposite was observed in cells when ADAMTS-1 was deleted via the CRISPR/Cas9 approach. The decline in ADAMTS-1 levels enhanced the phosphorylated form of Src and FAK. We also evaluated the activities of cellular Rho GTPases from cell lysates using the GLISA® kit. The Cdc42-GTP signal was significantly increased in the CRISPR ADAMTS-1 ES-2 cells. By a Förster resonance energy transfer (FRET) biosensor for Cdc42 activity in ES-2 cells we demonstrated that Cdc42 activity was strongly polarized at the leading edge of migrating cells with ADAMTS-1 deletion, compared to the wild type cells. As conclusion, ADAMTS-1 inhibits proliferation, polarization and migration.


Asunto(s)
Proteína ADAMTS1/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Proteína ADAMTS1/deficiencia , Proteína ADAMTS1/genética , Sistemas CRISPR-Cas/genética , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Femenino , Quinasa 1 de Adhesión Focal/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Fosforilación , ARN Guía de Kinetoplastida/metabolismo , Transducción de Señal , Familia-src Quinasas/metabolismo
9.
Rev. Soc. Bras. Med. Trop ; 54: e07552020, 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1155600

RESUMEN

Abstract INTRODUCTION: The intensification of research and innovation with the creation of networks of rapid and effective molecular tests as strategies for the end of tuberculosis are essential to avoid late diagnosis and for the eradication of the disease. We aimed to evaluate the cost-effectiveness of Xpert®MTB/RIF (Xpert) in the diagnosis of drug-resistant tuberculosis in reference units, in scenarios with and without subsidies, and the respective cost adjustment for today. METHODS: The analyses were performed considering as criterion of effectiveness, negative culture or clinical improvement in the sixth month of follow-up. The comparison was performed using two diagnostic strategies for the drug susceptibility test (DST), BactecTMMGITTM960 System, versus Xpert. The cost effectiveness and incremental cost-effectiveness ratio (ICER) were calculated and dollar-corrected for American inflation (US$ 1.00 = R$ 5,29). RESULTS: Subsidized Xpert had the lowest cost of US$ 33.48 (R$67,52) and the highest incremental average efficiency (13.57), thus being a dominated analysis. After the inflation was calculated, the mean cost was DST-MGIT=US$ 74.85 (R$ 396,73) and Xpert = US$ 37.33 (R$197,86) with subsidies. CONCLUSIONS: The Xpert in the diagnosis of TB-DR in these reference units was cost-effective with subsidies. In the absence of a subsidy, Xpert in TB-DR is not characterized as cost effective. This factor reveals the vulnerability of countries dependent on international organizations' subsidy policies.


Asunto(s)
Humanos , Tuberculosis/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Análisis Costo-Beneficio
10.
Steroids ; 161: 108680, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32562708

RESUMEN

The progression of cancer depends on the interaction between the cells and their microenvironment. Progesterone is a steroid and progestogen sex hormone produced by the corpus luteum, which is a transitory endocrine gland in female mammals and prepares the endometrium for implantation. Also, progesterone is involved in antitumorigenic process in different types of cancer. Our goal is to investigate the role of progesterone in cell invasion and migration. Ovarian cells were treated with different concentrations of progesterone. 500 nM or 1 µM progesterone decreased the migration of the cells in 24 h or less without affecting the viability. Immunoblot showed that treatment with 1 µM progesterone decreased the phosphorylated forms of Src and FAK, and the cells were less polarized. Our results suggest that progesterone interferes with migration and invasion of ovarian cells. Inhibitory experiments inferred the progesterone receptor playing a role in migration and invasion. Decreased phosphorylation of molecules involved in these processes was also found.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Neoplasias Ováricas/patología , Progesterona/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Femenino , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Humanos , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , Familia-src Quinasas/metabolismo
11.
Int J Mycobacteriol ; 9(1): 24-28, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32474484

RESUMEN

Background: Drug-resistant tuberculosis (TB) is an ongoing health threat, and the greatest challenge to adequate control of TB in many countries lies in the lack of proper laboratory drug-susceptibility test. The aim of this study was to evaluate the activity-based costs (ABC) of Kit SIRE Nitratase® (Kit SIRE) and compare its values with the conventional drug-susceptibility test. Methods: The ABC was calculated for three different approaches: Kit SIRE (clinical samples and cultures), proportion methods in Lowenstein Jensen (PM-LJ), and the Bactec™ MGIT™ 960 system based on Mycobacterial Research Laboratory's routine. Results: The ABC of Kit SIRE from cultures was US$ 148.54, while from clinical samples was US$ 136.12. In the case of conventional tests, the ABC of Bactec™ MGIT™ 960 was US$ 227.63 and of the PM-LJ was US$ 132.64. The Kit SIRE has a lower ABC when clinical samples are used instead of cultures. Compared to conventional tests, the ABC is similar to the PM-LJ and lower the Bactec™ MGIT™ 960. Conclusion: The Kit SIRE should be used as a screening method in clinical specimens and in culture for laboratories that do not have Bactec™ MGIT™ 960. Therefore, it can be incorporated into the routine of laboratories in countries with low resources and a high burden of TB and drug-resistant TB.


Asunto(s)
Antituberculosos/farmacología , Técnicas de Laboratorio Clínico/instrumentación , Mycobacterium tuberculosis/efectos de los fármacos , Juego de Reactivos para Diagnóstico/economía , Brasil , Técnicas de Laboratorio Clínico/economía , Recursos en Salud/economía , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana/economía , Centros de Atención Terciaria , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
12.
J Cell Physiol ; 235(1): 587-598, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31254281

RESUMEN

Laminin peptides influence cancer biology. We investigated the role of a laminin-derived peptide C16 regulating invadopodia molecules in human prostate cancer cells (DU145). C16 augmented invadopodia activity of DU145 cells, and stimulated expression Tks4, Tks5, cortactin, and membrane-type matrix metalloproteinase 1. Reactive oxygen species generation is also related to invadopodia formation. This prompted us to address whether C16 would induce reactive oxygen species generation in DU145 cells. Quantitative fluorescence and flow cytometry showed that the peptide C16 increased reactive oxygen species in DU145 cells. Furthermore, significant colocalization between Tks5 and reactive oxygen species was observed in C16-treated cells. Results suggested that the peptide C16 increased Tks5 and reactive oxygen species in prostate cancer cells. The role of C16 increasing Tks and reactive oxygen species are novel findings on invadopodia activity.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Laminina/farmacología , Podosomas/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Laminina/metabolismo , Masculino , Invasividad Neoplásica/patología , Neoplasias de la Próstata/metabolismo , Proteolisis/efectos de los fármacos
13.
Sci Rep ; 9(1): 17703, 2019 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-31776405

RESUMEN

Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel.


Asunto(s)
Antivirales/farmacología , Replicación Viral , Virus Zika/efectos de los fármacos , ortoaminobenzoatos/farmacología , Aminas/química , Animales , Antivirales/síntesis química , Sitios de Unión , Chlorocebus aethiops , Unión Proteica , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Células Vero , Proteínas Virales/química , Proteínas Virales/metabolismo , Virus Zika/fisiología , ortoaminobenzoatos/síntesis química
14.
Comun. ciênc. saúde ; 29(supl. 1): 34-38, ago. 2018. ilus
Artículo en Portugués | LILACS | ID: biblio-972695

RESUMEN

O manejo perioperatório qualificado, seguro e racional é hoje uma dasprincipais medidas de impactos em saúde. O objetivo deste relato deexperiência é apresentar a estruturação e o atual estágio de práticas deum modelo multiprofissional de manejo perioperatório em um hospitalpúblico do Distrito Federal (DF). Trata-se de uma iniciativa pioneiradentro da rede do Sistema Único de Saúde do DF, onde, por meio deestratégias racionais de gestão do processo de trabalho e da clínica,tem-se alcançado resultados promissores, quer em níveis de processosinstitucionais ou de manejo perioperatório qualificado e mais segurode pacientes candidatos e/ou submetidos à intervenção cirúrgica noserviço.


Asunto(s)
Humanos , Estructura de los Servicios , Grupo de Atención al Paciente , Atención Perioperativa , Servicios de Salud
15.
Viruses ; 10(5)2018 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-29758005

RESUMEN

The Zika fever is an arboviral disease resulting from the infection with Zika virus (ZIKV). The virus is transmitted to humans by the bite of Aedes mosquitos, mainly Aedes aegypti and Aedes albopictus. ZIKV has been detected for decades in African and Asian regions and, since 2007, has spread to other continents; among them, infections are most reported in the Americas. This can be explained by the presence of vectors in highly populated and tropical regions where people are susceptible to contamination. ZIKV has been considered by the World Health Organization a serious public health problem because of the increasing number of cases of congenital malformation and neurological disorders related to its infection, such as microcephaly, Guillain⁻Barré syndrome, meningoencephalitis, and myelitis. There is no vaccine or specific antiviral against ZIKV. The infection is best prevented by avoiding mosquito bite, and the treatment of infected patients is palliative. In this context, the search for efficient antivirals is necessary but remains challenging. Here, we aim to review the molecules that have been described to interfere with ZIKV life cycle and discuss their potential use in ZIKV therapy.


Asunto(s)
Antivirales/farmacología , Investigación Biomédica/tendencias , Infección por el Virus Zika/tratamiento farmacológico , Virus Zika/efectos de los fármacos , Aedes/virología , Américas , Animales , Brotes de Enfermedades , Humanos , Microcefalia/virología , Mosquitos Vectores/virología , Salud Pública , Saliva/virología
16.
PLoS One ; 12(11): e0187857, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29141010

RESUMEN

Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle.


Asunto(s)
Antivirales/aislamiento & purificación , Venenos de Crotálidos/química , Hepacivirus/efectos de los fármacos , Animales , Antivirales/química , Antivirales/farmacología , Línea Celular , Crotalus , Crotoxina/química , Crotoxina/farmacología , Cristalografía por Rayos X , Hepacivirus/fisiología , Humanos , Fusión de Membrana/efectos de los fármacos , Estructura Molecular , Fosfolipasas A2/química , Fosfolipasas A2/farmacología , Replicación Viral/efectos de los fármacos
17.
J. bras. patol. med. lab ; 53(2): 92-99, Jan.-Apr. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-841238

RESUMEN

ABSTRACT Introduction: Infections caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV) are a major public health problem. Objectives: The study aimed to detect HBsAg, anti-HBc, anti-HBs and anti-HCV among health professionals and users of the Brazilian Unified Health System [Sistema Único de Saúde (SUS)] in the city of Resende, Rio de Janeiro, and to describe the sociodemographic profile and background of exposure. Methods: A total of 585 samples were collected between May and June 2014, obtained from the Brazilian Notifiable Diseases Surveillance System [Sistema de Informação de Agravos de Notificação (SINAN)] data, which were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV. Results: The predominant age group observed was 30-44 years (n = 277; 47.3%), 54.87% (n = 321) were female and 271 (46.32%) self declared skin colour/ethnicity white. The married participants were 262 (44.78%), 42.22% graduated from high school (n = 247) and 174 were health professionals (29.74%). Four participants were anti-HCV reagents and 18 were anti-HBc reagents. From these, 15 participants were reactive for anti-HBs antibodies. Among health professionals, 68.8% were anti-HBs positive. And 63.9% of participants declared to be vaccinated against hepatitis B. Conclusion: The prevalence of 0.68% for HCV and 3.08% for anti-HBc are below that detected in the Southeast region from the last census in the capitals of Brazil. There is still a reduced acceptance among health professionals for HBV and HCV screening.


RESUMO Introdução: As infecções causadas pelo vírus da hepatite B (VHB) e C (VHC) constituem grave problema de saúde pública. Objetivos: O estudo visou detectar os marcadores HBsAg, anti-HBc, anti-HBs e anti-VHC em profissionais de saúde e usuários do Sistema Único de Saúde (SUS) no município de Resende, Rio de Janeiro, bem como descrever o perfil sociodemográfico e os antecedentes de exposição. Métodos: Foram avaliadas 585 amostras entre maio e junho de 2014, obtidas dos dados do Sistema de Informação de Agravos de Notificação (SINAN). Elas foram testadas para HBsAg, anti-HBc, anti-HBs e anti-VHC. Resultados: A faixa etária predominante observada foi de 30-44 anos (n = 277; 47,3%); 54,87% (n = 321) eram do sexo feminino e 271 (46,32%) se autodeclararam de cor da pele/etnia branca. Os participantes casados foram 262 (44,78%); 42,22% tinham o ensino médio (n = 247) e 174 eram profissionais de saúde (29,74%). Quatro participantes eram anti-VHC reagentes e 18, reagentes para anti-HBc. Destes, 15 eram anti-HBs reagentes (aHBs+). Nos profissionais de saúde, 68,8% possuem aHbs+. Em relação à vacinação contra hepatite B, 63,9% declararam possuí-la. Conclusão: As prevalências 0,68% de VHC e de 3,08% de anti-HBc estão abaixo da detectada na região Sudeste no último censo nas capitais do Brasil. Há ainda reduzida adesão dos profissionais de saúde à testagem para VHB e VHC.

18.
PLoS One ; 11(10): e0165061, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27764205

RESUMEN

Proteins secreted in the extracellular matrix microenvironment (ECM) by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been implicated in tissue remodeling events observed in cancer development, growth and progression. Here we investigated the subcellular localization of ADAMTS-1 in normal-like (MCF10-A) and tumoral (MCF7 and MDA-MB-231) human breast cells. ADAMTS-1 is a secreted protease found in the extracellular matrix. However, in this study we show for the first time that ADAMTS-1 is also present in the nuclei and nucleoli of the three mammary cell lines studied here. Our findings indicate that ADAMTS-1 has proteolytic functions in the nucleus through its interaction with aggrecan substrate.


Asunto(s)
Proteína ADAMTS1/metabolismo , Neoplasias de la Mama/enzimología , Núcleo Celular/enzimología , Agrecanos/metabolismo , Línea Celular , Femenino , Humanos , Células MCF-7 , Microambiente Tumoral
20.
Transfus Med Hemother ; 43(2): 137-41, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27226795

RESUMEN

BACKGROUND: This paper describes the transmission of hepatitis A virus (HAV) to two blood recipients from a healthy donor that later presented to the blood bank with jaundice. METHODS: The RNA of HAV was detected by qualitative nested reverse transcription polymerase chain reaction (nested RT-PCR) and quantified by real-time RT-PCR. HAV RNA samples were genotyped by direct sequencing of PCR products. A sequence from a fragment of 168 bp from the VP1/2A HAV region was used to construct a phylogenetic tree. CASE REPORT: A 31-year-old male donor accepted for donation of a whole blood unit returned to the blood bank with clinical jaundice 20 days after donation. His serological and NAT tests were negative for HBV and HCV. Serological tests for HAV IgM and IgG were negative on donation sample but positive on follow-up sample, confirming donor's HAV acute infection. Both recipients of red blood cells (R1) and platelet concentrate (R2) from the same implicated donation were HAV IgM-negative and IgG-positive. Qualitative PCR was positive on samples from all three individuals and phylogenetic analysis of viruses proved HAV transmission to the two recipients of blood products. HAV viral load on donor follow-up sample and the platelet recipient was 1.3 and 1.5 × 10(3) IU/ml, respectively. The RBC recipient, also infected by HCV, was undergoing bone marrow transplantation and died from fulminant hepatitis, 26 days after the implicated HAV transfusion. CONCLUSION: The blood donor, a garbage collector, spontaneously returned to the blood bank when developing jaundice. This highlights the importance of donor education to immediately report to blood banks of any signs and symptoms related to infectious disease developed after blood donation. The fact that one immunocompromised patient with HCV infection died from fulminant hepatitis after receiving a HAV-contaminated platelet transfusion underpins the importance of a HAV vaccination program for these group of patients.

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