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1.
Biomater Adv ; 151: 213441, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37167747

RESUMO

Bisphosphonates are a class of drugs that induce bone cancer cell death and favor bone regeneration, making them suitable for bone cancer treatment. However, when combined with bioactive glasses to enhance bone regeneration, a chemical bond between biphosphonates and the glass surface inactivates their mechanism of action. A new colloidal hydrogel-based drug delivery system could overcome that limitation once bisphosphonates, such as zoledronic acid (ZA), are incorporated into hydrogel micelles, avoiding their interaction with the glass surface. In this work, we proposed formulations based on a poloxamer 407 thermo-responsive hydrogel matrix containing holmium-doped bioactive glass nanoparticles and different concentrations (0.05 and 5 mg/mL) of ZA. We characterized the influence of the glass and the ZA on the hydrogel properties. In addition, a drug concentration screening was performed, and biological characterizations evaluated the best result. The biological characterization consisted of evaluating cytotoxicity and in vitro bone regeneration ability through cell migration and quantification of genes related to osteogeneses through RT-PCR. The results suggest that the addition of glasses and ZA to the poloxamer did not significantly influence the sol-gel transition of the hydrogels (around 13 °C) regardless of the ZA content. However, the ZA at high concentration (PL-ZA100) decreased the enthalpy of gel formation from 68 to 43 kJ.mol-1 when compared with the pure hydrogel formulation (PL), suggesting a water structurer role of ZA, which is withdrawn when glass particles are added to the system (PL-BG5Ho-ZA100). Solid-state 31P nuclear resonance spectroscopy results showed that part of the ZA is chemically bonded to the glass surface, which explains the withdrawal in the water structurer role of ZA when the glasses were incorporated into the hydrogel. Besides, based on the drug release results, we proposed a model where part of the ZA is "free," encapsulated in the hydrogel matrix, while another part of the ZA is bonded to the glass surface. Finally, considering the in vitro results and our proposed model, the ratio between "free" and "bonded" ZA in our drug delivery systems showed in vitro evidence of a cancer treatment that selectively kills osteosarcoma cells while still favoring an osteogenic microenvironment. By overcoming the limitation of combining bisphosphonates with bioactive glasses, hydrogel-based drug delivery systems can be a solution for the development of new formulations proposed for bone cancer treatment in conjunction with bone regeneration.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Difosfonatos/farmacologia , Hidrogéis , Regeneração Óssea , Sistemas de Liberação de Medicamentos , Ácido Zoledrônico , Neoplasias Ósseas/tratamento farmacológico , Microambiente Tumoral
2.
Materials (Basel) ; 15(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36556893

RESUMO

The treatment of bone cancer involves tumor resection followed by bone reconstruction of the defect caused by the tumor using biomaterials. Additionally, post-surgery protocols cover chemotherapy, radiotherapy, or drug administration, which are employed as adjuvant treatments to prevent tumor recurrence. In this work, we reviewed new strategies for bone cancer treatment based on bioactive glasses as carriers of cancer-targeted and other drugs that are intended for bone regeneration in conjunction with adjuvant treatments. Drugs used in combination with bioactive glasses can be classified into cancer-target, osteoclast-target, and new therapies (such as gene delivery and bioinorganic). Microparticulated, nanoparticulated, or mesoporous bioactive glasses have been used as drug-delivery systems. Additionally, surface modification through functionalization or the production of composites based on polymers and hydrogels has been employed to improve drug-release kinetics. Overall, although different drugs and drug delivery systems have been developed, there is still room for new studies involving kinase inhibitors or antibody-conjugated drugs, as these drugs have been poorly explored in combination with bioactive glasses.

3.
Econ Hum Biol ; 43: 101051, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34411841

RESUMO

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg. The model has been used to produce nowcasts and forecasts at various stages of the crisis. We focus here on two key moments in time, namely the deconfinement period following the first lockdown, and the onset of the second wave. In May 2020, we predicted a high risk of a second wave that was mainly explained by the resumption of social life, low participation in large-scale testing, and reduction in teleworking practices. Simulations conducted 5 months later reveal that managing the second wave with moderately coercive measures has been epidemiologically and economically effective. Assuming a massive third (or fourth) wave will not materialize in 2021, the real GDP loss due to the second wave will be smaller than 0.4 percentage points in 2020 and 2021.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Humanos , Luxemburgo/epidemiologia , Política Pública , SARS-CoV-2
4.
Health Policy ; 125(8): 972-980, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34090724

RESUMO

Testing is widely seen as one core element of a successful strategy to curtail the COVID-19 pandemic and many countries have increased their efforts to provide testing at large scale. As most democratic governments refrain from enacting mandatory testing, a key emerging challenge is to increase voluntary participation. Using behavioural economics insights complemented with data from a novel survey in the US and a survey experiment in Luxembourg, we examine behavioural factors associated with the individual willingness to get tested (WTT). In our analysis, individual characteristics that correlate positively with WTT include age, altruism, conformism, the tendency to abide by government-imposed rules, concern about contracting COVID-19, and patience. Risk aversion, unemployment, and conservative political orientation correlate negatively with WTT. Building on and expanding these insights may prove fruitful for policy to effectively raise people's propensity to get tested.


Assuntos
COVID-19 , Teste para COVID-19 , Economia , Economia Comportamental , Humanos , Pandemias , SARS-CoV-2
5.
Materials (Basel) ; 14(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802678

RESUMO

Holmium-containing bioactive glasses can be applied in bone cancer treatment because the holmium content can be neutron activated, having suitable properties for brachytherapy applications, while the bioactive glass matrix can regenerate the bone alterations induced by the tumor. To facilitate the application of these glasses in clinical practice, we proposed a composite based on Poloxamer 407 thermoresponsive hydrogel, with suitable properties for applications as injectable systems. Therefore, in this work, we evaluated the influence of holmium-containing glass particles on the properties of Poloxamer 407 hydrogel (20 w/w.%), including self-assembly ability and biological properties. 58S bioactive glasses (58SiO2-33CaO-9P2O5) containing different Ho2O3 amounts (1.25, 2.5, 3.75, and 5 wt.%) were incorporated into the hydrogel. The formulations were characterized by scanning electron microscopy, differential scanning calorimetry, rheological tests, and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT cell viability against pre-osteoblastic and osteosarcoma cells. The results evidenced that neither the glass particles dispersed in the hydrogel nor the holmium content in the glasses significantly influenced the hydrogel self-assembly ability (Tmic ~13.8 °C and Tgel ~20 °C). Although, the glass particles considerably diminished the hydrogel viscosity in one order of magnitude at body temperature (37 °C). The cytotoxicity results evidenced that the formulations selectively favored pre-osteoblastic cell proliferation and osteosarcoma cell death. In conclusion, the formulation containing glass with the highest fraction of holmium content (5 wt.%) had the best biological results outcomes aiming its application as theragenerative materials for bone cancer treatment.

6.
Sci Rep ; 9(1): 11923, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417135

RESUMO

Cryptococcosis is a fungal disease caused by C. neoformans. To adapt and survive in diverse ecological niches, including the animal host, this opportunistic pathogen relies on its ability to uptake nutrients, such as carbon, nitrogen, iron, phosphate, sulfur, and amino acids. Genetic circuits play a role in the response to environmental changes, modulating gene expression and adjusting the microbial metabolism to the nutrients available for the best energy usage and survival. We studied the sulfur amino acid biosynthesis and its implications on C. neoformans biology and virulence. CNAG_04798 encodes a BZip protein and was annotated as CYS3, which has been considered an essential gene. However, we demonstrated that CYS3 is not essential, in fact, its knockout led to sulfur amino acids auxotroph. Western blots and fluorescence microscopy indicated that GFP-Cys3, which is expressed from a constitutive promoter, localizes to the nucleus in rich medium (YEPD); the addition of methionine and cysteine as sole nitrogen source (SD-N + Met/Cys) led to reduced nuclear localization and protein degradation. By proteomics, we identified and confirmed physical interaction among Gpp2, Cna1, Cnb1 and GFP-Cys3. Deletion of the calcineurin and GPP2 genes in a GFP-Cys3 background demonstrated that calcineurin is required to maintain Cys3 high protein levels in YEPD and that deletion of GPP2 causes GFP-Cys3 to persist in the presence of sulfur amino acids. Global transcriptional profile of mutant and wild type by RNAseq revealed that Cys3 controls all branches of the sulfur amino acid biosynthesis, and sulfur starvation leads to induction of several amino acid biosynthetic routes. In addition, we found that Cys3 is required for virulence in Galleria mellonella animal model.


Assuntos
Aminoácidos Sulfúricos/biossíntese , Vias Biossintéticas , Calcineurina/metabolismo , Cryptococcus neoformans/metabolismo , Proteínas Fúngicas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Vias Biossintéticas/genética , Cryptococcus neoformans/genética , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/patogenicidade , Regulação Fúngica da Expressão Gênica , Ontologia Genética , Proteínas de Fluorescência Verde/metabolismo , Modelos Biológicos , Estado Nutricional , Transporte Proteico , Proteômica , Enxofre/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Virulência/genética
7.
Arq. bras. neurocir ; 35(1): 97-100, Mar. 2016. ilus, tab
Artigo em Português | LILACS | ID: biblio-837323

RESUMO

Abscesso espinhal epidural é uma doença rara de diagnóstico difícil, sendo que o principal fator prognóstico é o diagnóstico breve. A maioria dos pacientes, porém, tem o diagnóstico tardio, quando já existem sintomas neurológicos que podem permanecer após o tratamento. Na maioria dos casos, os sintomas iniciais são dor nas costas, febre e paralisia. O tratamento é feito à base de antibioticoterapia empírica e, caso não haja contraindicação, descompressão e drenagem cirúrgica. Relata-se o caso de uma paciente que sofreu paralisia súbita nos membros inferiores. Inicialmente, havia suspeita de mielite transversa, mas a evolução do caso permitiu o diagnóstico de abscesso espinhal epidural emT6, T7 e T8, causada por disseminação hematogênica de Staphylococcus aureus.


Spinal epidural abscess is a rare and difficult disease to diagnose, and the main prognostic factor is the early diagnosis. Most patients, however, have their diagnosis delayed to when they already have neurological symptoms that may remain after treatment. In most cases, the initial symptoms are back pain, fever and paralysis. Treatment is based on empirical antibiotic therapy and, if there is no contraindication, decompression and surgical drainage. We report the case of a patient who suffered sudden paralysis of the inferior members. Initially suspected as transversemyelitis, the case evolved, allowing the diagnosis of spinal epidural abscess in T6, T7 and T8, caused by hematogenous spread of Staphylococcus aureus.


Assuntos
Humanos , Feminino , Adolescente , Abscesso Epidural/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Infecções Estafilocócicas/complicações , Staphylococcus aureus , Paralisia/etiologia
8.
Fungal Genet Biol ; 70: 12-23, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25011011

RESUMO

Fungal infections are often difficult to treat due to the inherent similarities between fungal and animal cells and the resulting host toxicity from many antifungal compounds. Cryptococcus neoformans is an opportunistic fungal pathogen of humans that causes life-threatening disease, primarily in immunocompromised patients. Since antifungal therapy for this microorganism is limited, many investigators have explored novel drug targets aim at virulence factors, such as the ability to grow at mammalian physiological temperature (37°C). To address this issue, we used the Agrobacterium tumefaciens gene delivery system to create a random insertion mutagenesis library that was screened for altered growth at elevated temperatures. Among several mutants unable to grow at 37°C, we explored one bearing an interruption in the URA4 gene. This gene encodes dihydroorotase (DHOase) that is involved in the de novo synthesis of pyrimidine ribonucleotides. Loss of the C. neoformans Ura4 protein, by targeted gene interruption, resulted in an expected uracil/uridine auxotrophy and an unexpected high temperature growth defect. In addition, the ura4 mutant displayed phenotypic defects in other prominent virulence factors (melanin, capsule and phospholipase) and reduced stress response compared to wild type and reconstituted strains. Accordingly, this mutant had a decreased survival rate in macrophages and attenuated virulence in a murine model of cryptococcal infection. Quantitative PCR analysis suggests that this biosynthetic pathway is induced during the transition from 30°C to 37°C, and that transcriptional regulation of de novo and salvage pyrimidine pathway are under the control of the Ura4 protein.


Assuntos
Cryptococcus neoformans/fisiologia , Pirimidinas/biossíntese , Animais , Antifúngicos/farmacologia , Linhagem Celular , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Temperatura Alta , Macrófagos/microbiologia , Redes e Vias Metabólicas , Camundongos Endogâmicos C57BL , Mutação , Estresse Fisiológico , Virulência
9.
PLoS One ; 6(6): e21465, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21731758

RESUMO

Transforming growth factor beta (TGF-ß) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-ß production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-ß and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-ß produced by ECs are sufficient to induce a self-sustaining autocrine TGF-ß signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-ß to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-ß receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-ß produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-ß receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-ß production. In summary, our findings indicate that the amplitude of TGF-ß signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth.


Assuntos
Células Epitelioides/enzimologia , Células Epitelioides/microbiologia , Espaço Intracelular/microbiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mycobacterium avium/crescimento & desenvolvimento , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Epitelioides/efeitos dos fármacos , Interleucina-13/farmacologia , Espaço Intracelular/efeitos dos fármacos , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium avium/efeitos dos fármacos , Receptores de Interleucina-4/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
BMC Cancer ; 11: 296, 2011 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-21756336

RESUMO

BACKGROUND: Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd(2) [S((-))C(2), N-dmpa](2) (µ-dppe)Cl(2)} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies. METHODS: B16F10-Nex2 cells were treated in vitro with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated in vitro with C7a. RESULTS: Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages in vitro, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells. CONCLUSIONS: The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Mitocondriais/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Paládio/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/fisiologia , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Estrutura Molecular , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Paládio/química , Paládio/metabolismo , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
Cad Saude Publica ; 24(8): 1835-45, 2008 Aug.
Artigo em Português | MEDLINE | ID: mdl-18709224

RESUMO

This study aimed to determine the profile of the elderly population (>or= 60 years) in two poor municipalities in North and Northeast Brazil in 2005. Using a cross-sectional survey with a systematic sample, previously trained interviewers applied a standard household questionnaire on demographic characteristics, socioeconomic status, household conditions, physical activity, immunization status, health problems, and expenditures on medicines. Of the total sample (n = 1,013), 528 lived in Caracol, Piauí State, and 478 in Garrafão do Norte, Pará State. 56% were 60-69 years old, 10% lived alone, 69% were illiterate, 8% had a family income less than the minimum wage, 24% of the households had a flush toilet, 60% had a radio, television, and refrigerator, 88% reported at least one chronic disease, 47% had to purchase all their medicines out-of-pocket, 84% had received influenza vaccination, and 90% were able to perform normal activities of daily living. Elderly people included in this study showed poor household conditions, inadequate access to health care, and high levels of morbidity.


Assuntos
Idoso/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Serviços de Saúde para Idosos/estatística & dados numéricos , Condições Sociais/estatística & dados numéricos , Distribuição por Idade , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doença Crônica , Estudos Transversais , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , População Rural , Fatores Socioeconômicos , População Urbana/estatística & dados numéricos
12.
Cad. saúde pública ; 24(8): 1835-1845, ago. 2008. tab
Artigo em Português | LILACS | ID: lil-488934

RESUMO

Determinar o perfil de pessoas com 60 anos ou mais de idade residentes em dois municípios pobres nas regiões Norte e Nordeste do Brasil em 2005. Por meio de delineamento transversal e amostragem sistemática, aplicou-se a idosos questionário padronizado domiciliar buscando informações sobre suas características demográficas, nível sócio-econômico, condição de habitação e saneamento, realização de atividades físicas, estado vacinal, problemas de saúde e consumo de medicamentos. Dentre os 1.013 idosos identificados, 528 residiam no Município de Caracol, Piauí, e 487 em Garrafão do Norte, Pará. Cinqüenta e seis por cento possuíam entre 60 e 69 anos de idade, 10 por cento viviam sozinhos, 69 por cento não eram alfabetizados, 8 por cento tinham renda familiar inferior a 1 salário mínimo; em somente 24 por cento dos seus domicílios havia sanitário com descarga e 60 por cento possuíam rádio, televisão e geladeira; 88 por cento referiram pelo menos uma doença crônica, 47 por cento tinham de comprar todos os medicamentos consumidos, 84 por cento foram vacinados contra influenza e pelo menos 90 por cento disseram-se capazes de realizar atividades da vida diária. Entre os idosos estudados, as condições de moradia mostraram-se inadequadas, o acesso a bens e serviços insuficiente e elevado padrão de morbidade.


This study aimed to determine the profile of the elderly population (> 60 years) in two poor municipalities in North and Northeast Brazil in 2005. Using a cross-sectional survey with a systematic sample, previously trained interviewers applied a standard household questionnaire on demographic characteristics, socioeconomic status, household conditions, physical activity, immunization status, health problems, and expenditures on medicines. Of the total sample (n = 1,013), 528 lived in Caracol, Piauí State, and 478 in Garrafão do Norte, Pará State. 56 percent were 60-69 years old, 10 percent lived alone, 69 percent were illiterate, 8 percent had a family income less than the minimum wage, 24 percent of the households had a flush toilet, 60 percent had a radio, television, and refrigerator, 88 percent reported at least one chronic disease, 47 percent had to purchase all their medicines out-of-pocket, 84 percent had received influenza vaccination, and 90 percent were able to perform normal activities of daily living. Elderly people included in this study showed poor household conditions, inadequate access to health care, and high levels of morbidity.


Assuntos
Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Idoso/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Serviços de Saúde para Idosos/estatística & dados numéricos , Condições Sociais/estatística & dados numéricos , Distribuição por Idade , Brasil/epidemiologia , Doença Crônica , Estudos Transversais , Nível de Saúde , Indicadores Básicos de Saúde , Vigilância da População , População Rural , Fatores Socioeconômicos , População Urbana/estatística & dados numéricos
13.
Cancer Sci ; 99(5): 920-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18312464

RESUMO

Increasing evidence indicates that tumors require a constant influx of myelomonocytic cells to support their malignant behavior. This is caused by tumor-derived factors, which recruit and induce functional differentiation of myelomonocytic cells, most of which are macrophages. Although myeloid lineages are the classical precursors of macrophages, B-lymphoid lineages such as B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, are also able to migrate to inflammatory sites and differentiate into mononuclear phagocytes exhibiting macrophage-like phenotypes. Here we examined the interplay of B-1 cells and tumor cells, and checked whether this interaction provides signals to influence melanoma cells metastases. Using in vitro coculture experiments we showed that B16, a murine melanoma cell line, and B-1 cells physically interact. Moreover, interaction of B16 with B-1 cells leads to up-regulation of metastasis-related gene expression (MMP-9 and CXCR-4), increasing its metastatic potential, as revealed by experimental metastases assays in vivo. We also provide evidence that B16 cells exhibit markedly up-regulated phosphorylation of the extracellular signal-regulated kinase (ERK) when cocultured with B-1 cells. Inhibition of ERK phosphorylation induced by B-1 cells with inhibitors of MEK1/2 strongly suppressed the induction of MMP-9 and CXCR-4 mRNA expression and impaired the increased metastatic behavior of B16. In addition, constitutive levels of ERK1/2 phosphorylation in B-1 cells are necessary for their commitment to affect the metastatic potential of B16 cells. Our findings show for the first time that B-1 lymphocytes can contribute to tumor cell properties required for invasiveness during metastatic spread.


Assuntos
Linfócitos B/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Melanoma/enzimologia , Animais , Feminino , Melanoma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Fosforilação , Células Tumorais Cultivadas , Regulação para Cima
14.
Int J Exp Pathol ; 87(3): 185-95, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16709227

RESUMO

Alterations in transforming growth factor (TGF)-beta signalling have been frequently implicated in human cancer, and an important mechanism underlying its pro-oncogenic nature is suppression of the host antitumour immune response. Considering the immunosuppressive effect of TGF-beta, we asked whether human tumour cells, known to secrete TGF-beta in culture, would survive and grow when implanted into the peritoneal cavity of immunocompetent mice. Therefore, we developed a xenogeneic model where mice were intraperitoneally (i.p.) injected with a TGF-beta-secreting human colorectal adenocarcinoma cell line, LISP-A10. Although animals did not develop macroscopic tumours, the recovery and isolation of human tumour cells was achieved when an inflammatory environment was locally induced by the administration of complete Freund's adjuvant (CFA). This procedure significantly increased TGF-beta concentrations in the peritoneal fluid and was accompanied by impaired activation of the host-specific immune response against LISP-A10 cells. Furthermore, inflammatory lesions resembling human inflammatory pseudotumours (IPTs) were observed on the surface of i.p. organs. These lesions could be induced by either injection of LISP-A10 cells, cells-conditioned medium or recombinant TGF-beta but only after administration of CFA. In addition, host cyclooxygenase-2 and kinin receptors played an important role in the induction of TGF-beta-mediated IPT-like lesions in our experimental model.


Assuntos
Granuloma de Células Plasmáticas/imunologia , Fator de Crescimento Transformador beta/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Adjuvante de Freund/farmacologia , Imunoglobulinas/sangue , Imuno-Histoquímica/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Transplante de Neoplasias , Receptor B1 da Bradicinina/genética , Receptor B1 da Bradicinina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/análise , Transplante Heterólogo
15.
Int J Cancer ; 114(3): 356-63, 2005 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-15573371

RESUMO

Two murine melanoma cell lines, Tm1 and Tm5, were derived from a nontumorigenic lineage of pigmented murine melanocytes, melan-a. Both Tm1 and Tm5 are invariably tumorigenic in syngeneic mice when inoculated s.c. in doses higher than 10(4) cells; 10(3) or fewer cells rarely give rise to tumors. We demonstrate that subtumorigenic inocula of Tm1 or Tm5 cells (10(3)) as well as of a known murine melanoma cell line (B16F10) develop as vigorously growing tumor grafts only when coinoculated with apoptotic, but not necrotic cells. The presence of apoptotic cells correlates with a transient inflammatory infiltrate, composed mainly of neutrophils and macrophages. Kinin B1 receptor-deficient mice, which have impaired transmigration of neutrophils to inflamed tissues, had significant growth inhibition of subtumorigenic doses of melanoma cells coinjected with apoptotic cells. Using the same model, tumor take in athymic mice was similar to that seen in wild-type mice, suggesting that a T cell-dependent inflammatory response is not necessary to promote the survival and growth of subtumorigenic doses of melanoma cells. Taken together, our results describe how tumor engraftment and growth can be profoundly affected by microenvironmental alterations in response to the presence of apoptotic cells. Disrupting the delicate balance between apoptotic cells and leukocyte infiltration may provide potentially important insights for understanding and interfering with tumor cell viability during treatment with either gamma-radiation or apoptosis-inducing drugs.


Assuntos
Apoptose/imunologia , Sobrevivência Celular , Inflamação , Melanoma/patologia , Invasividade Neoplásica/fisiopatologia , Neoplasias Cutâneas/patologia , Animais , Transformação Celular Neoplásica , Raios gama , Leucócitos , Melanócitos , Camundongos , Camundongos Nus , Neoplasias Experimentais , Infiltração de Neutrófilos , Células Tumorais Cultivadas
16.
Rev. paul. pediatr ; 8(29): 51-4, abr.-jun. 1990. tab
Artigo em Português | LILACS | ID: lil-89220

RESUMO

Com objetivo de analisar o impacto nutricional de um programa de suplementaçäo alimentar com leite fluído, avaliaram-se por meio de medidas antropométricas e análise retrospectiva de prontuários, 249 crianças (0 - 59 meses) em um centro de saúde de Santos (S.P.). Concluiu-se que o critério de ingresso ao programa segundo a Secretaria da Saúde (relaçäo peso/idade inferior do percentil 10) permite a inclusäo de um grande número de crianças sem comprometimento nutricional, que pouco se beneficiam da suplementaçäo, ao contrário dos verdadeiros desnutridos


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Masculino , Feminino , Transtornos da Nutrição Infantil , Leite , Programas de Nutrição , Fenômenos Fisiológicos da Nutrição do Lactente , Fatores Socioeconômicos , Peso-Estatura , Brasil , Bovinos , Estado Nutricional , Estudos Retrospectivos
17.
São Paulo; SES/SP; mar. 1990. 84 p. ilus, tab.
Não convencional em Português | LILACS, Sec. Est. Saúde SP, SESSP-ACVSES | ID: biblio-1070630

RESUMO

A reorganização do setor saúde, tanto no aspecto jurídico-administrativo quanto na concepção do modelo assistencial, através da criação do Sistema Único de Saúde(SUS), consagrado na Constituição Brasileira, promulgada em 05/10/88, tem repercussões imediatas sobre o papel das Secretarais de Saúde dos Estados na conformação do Sistema Estadual de Saúde. Embora estejamos em plena fase de transição para a estruturação definitiva do sistema de saúde, algumas coordenadas estão dadas em relação as competências - normalização, coordenação e gestão dos serviços de saúde - de cada instância. Neste contexto o município amplia sua responsabilidade na execução das ações de saúde, incorporando definitivamente a assistência médica. Concomitantemente, o estado retrai sua participação na gerência direta dos serviços de saúde. Esta conjuntura determina uma nova dimensão na relação estado/município com reflexos imediatos sobre a atuação dos técnicos do nível estadual que abandonam uma postura historicamente intervencionista para assumir a de caráter assessor, transferindo conhecimento técnico e sistematizando a experiência...


Assuntos
Inovação Organizacional , Planejamento em Saúde , Planos Diretores , Planos e Programas de Saúde , Programas Governamentais , Sistemas de Saúde
18.
In. Associaçäo Brasileira de Pós-Graduaçäo em Saúde Coletiva. Universidade de Campinas. Departamento de Medicina Preventiva e Social. Anais do I Congresso Brasileiro de Epidemiologia. Epidemiologia e desigualdade social: os desafios do final do século. Rio de Janeiro, Associaçäo Brasileira de Pós-Graduaçäo em Saúde Coletiva, 1990. p.33-6.
Monografia em Português | LILACS | ID: lil-127352

RESUMO

A regionalizaçäo das atividades de vigilância epidemiológica no país, na perspectiva de um sistema único de saúde, deve levar em consideraçäo a redefiniçäo das funçöes próprias de cada um dos três níveis básicos deste sistema: o nível local, abrangendo um ou mais municípios, parte de um município, e compreendendo um conjunto de unidades prestadoras de serviço; o intermediário ou estadual e o nível nacional. O papel de cada nível poderá variar de acordo com as características e da situaçäo epidemiológica do agravo ou da doença, objeto de vigilância e também de acordo com o grande desenvolvimento, disponibilidade de recursos e capacidade técnico-operacional das diferentes áreas geográficas


Assuntos
Cidades , Brasil , Regionalização da Saúde , Serviços de Saúde/organização & administração
19.
Medicina (Ribeiräo Preto) ; 19(3/4): 103-10, jul.-dez. 1986. ilus, tab
Artigo em Português | LILACS | ID: lil-41397

RESUMO

Realizou-se um estudo para verificar a prevalência de infecçäo leptospirótica entre os servidores do biotério geral do Campus de Ribeiräo Preto - USP a partir do diagnóstico de leptospirose em L.F.E., 21 anos, uma vez que o referido paciente há um ano exercia a funçäo de tratador de animais no canil deste biotério. Esta prevalência de infecçäo leptospirótica foi avaliada através da reaçäo de soroaglutinaçäo microscópica para leptospirose realizada pelo Instituto Adolfo Lutz de Säo Paulo, sendo que todos os funcionários do biotério foram submetidos ao exame. Também foram incluídos neste levantamento nove membros da família do paciente L.F.E. (seus pais, cinco irmäos, cunhada e sobrinha), por residirem nas proximidades e frequentarem o biotério. Foi realizada nesta mesma populaçäo um inquérito epidemiológico através de um questionário dirigido, buscando com este detectar os fatores de risco associados à infecçäo leptospirótica. A prevalência de infecçäo leptospirótica encontrada foi de 11,4% (04 reaçöes positivas, num total de 35 amostras de sangue


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Doenças Profissionais/epidemiologia , Leptospirose/epidemiologia , Testes de Aglutinação , Brasil , Leptospirose/diagnóstico
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