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1.
Emerg Infect Dis ; 29(12): 2553-2556, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37916983

RESUMO

We report a massive mortality of 5,224 sea lions (Otaria flavescens) in Peru that seemed to be associated with highly pathogenic avian influenza A(H5N1) virus infection. The transmission pathway may have been through the close contact of sea lions with infected wild birds. We recommend evaluating potential virus transmission among sea lions.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Leões-Marinhos , Animais , Animais Selvagens
2.
Rev. Fac. Cienc. Méd. (Quito) ; 47(2): 9-17, Jul 01, 2022.
Artigo em Espanhol | LILACS | ID: biblio-1526654

RESUMO

Objetivo: Determinar los factores de riesgo de patologías lumbares en pacientes empleados y afiliados al sistema de salud, a partir de la exploración física, hábitos, antecedentes personales y factores de riesgo laborales. Material y Métodos: El diseño del estudio es retrospectivo, transversal. En una muestra de 668 adultos trabajadores del Ecuador, se aplicó y evaluó el modelo predictivo de respuesta binaria logit para identificar factores de riesgo y se usaron métodos de aprendizaje supervisado (árboles de clasificación) para clasificar a los pacientes según el grado de patología lumbar. Resultados: El modelo predictivo logístico presentó una sensibilidad del 62,5%, una especificidad del 63,7%, el área bajo la curva ROC fue 0,63 y se determinó una precisión del 63,4%.Conclusión: Los factores que aumentan el riesgo de la patología de columna lumbar más frecuente (lumbalgia) y en orden de importancia en los pacientes son: menor edad, sexo femenino, tienden a exponerse a factores de riesgo psicosocial en su trabajo


Objective: Determine the risk factors of lumbar pathologies in patients employed and affi-liated with the health system, based on physical examination, habits, personal history, and occupational risk factors.Materials and Methods: The study design is retrospective, cross-sectional. In a sample of 668 adult workers from Ecuador. The binary logit response predictive model was applied to identify risk factors and supervised learning methodology (classification trees) was used to classify patients according to the degree of lumbar pathology.Results: The logistic predictive model has a sensitivity of 62.5%, a specificity of 63.7%, the area under the ROC curve was 0.63, and precision of 63.4% was determined.Conclusion: The factors that increase the risk of the most frequent lumbar pathology (low back pain) in order of importance in patients are: younger age, female sex, tend to be expo-sed to psychosocial risk factors at work, and lower risk of having mechanical factors.


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Riscos Ocupacionais , Saúde Ocupacional/estatística & dados numéricos , Dor Lombar , Coluna Vertebral/anormalidades , Medição de Risco , Dor Musculoesquelética
3.
Expert Rev Pharmacoecon Outcomes Res ; 21(4): 785-798, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32686530

RESUMO

Objectives: To estimate the clinical and economic burden of type 2 diabetes (T2D) in established (EST) and emerging markets (EMG).Methods: Three systematic literature reviews were conducted in MEDLINE and Embase to capture all relevant publications reporting 1) the epidemiology of T2D and complications in T2D and 2) the economic burden of T2D and associated complications.Results: In total, 294 studies were included in this analysis. Evidence indicates a high and increasing overall prevalence of T2D globally, ranging up to 23% in EMG markets and 14% in EST markets. Undiagnosed cases were higher in EMG versus EST markets (up to 67% vs 38%), potentially due to a lack of education and disease awareness in certain regions, that could lead to important clinical and economic consequences. Poor glycemic control was associated with the development of several complications (e.g. retinopathy, cardiovascular diseases and nephropathy) that increase the risk of morbidity and mortality. Direct costs were up to 9-fold higher in patients with vs without T2D-related complications.Conclusions: The burden of T2D, related complications and inherent costs are higher in emerging versus established market countries. This review explores potential strategies to reduce costs and enhance outcomes of T2D treatment in developing countries.


Assuntos
Efeitos Psicossociais da Doença , Complicações do Diabetes/economia , Diabetes Mellitus Tipo 2/economia , Países Desenvolvidos , Países em Desenvolvimento , Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Saúde Global , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Prevalência
4.
Pharmaceuticals (Basel) ; 13(7)2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32707662

RESUMO

Glioma is the most frequent and aggressive type of brain neoplasm, being anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), its most malignant forms. The survival rate in patients with these neoplasms is 15 months after diagnosis, despite a diversity of treatments, including surgery, radiation, chemotherapy, and immunotherapy. The resistance of GBM to various therapies is due to a highly mutated genome; these genetic changes induce a de-regulation of several signaling pathways and result in higher cell proliferation rates, angiogenesis, invasion, and a marked resistance to apoptosis; this latter trait is a hallmark of highly invasive tumor cells, such as glioma cells. Due to a defective apoptosis in gliomas, induced autophagic death can be an alternative to remove tumor cells. Paradoxically, however, autophagy in cancer can promote either a cell death or survival. Modulating the autophagic pathway as a death mechanism for cancer cells has prompted the use of both inhibitors and autophagy inducers. The autophagic process, either as a cancer suppressing or inducing mechanism in high-grade gliomas is discussed in this review, along with therapeutic approaches to inhibit or induce autophagy in pre-clinical and clinical studies, aiming to increase the efficiency of conventional treatments to remove glioma neoplastic cells.

5.
IET Nanobiotechnol ; 14(3): 191-197, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32338626

RESUMO

In the present work, the preparation, characterisation, and efficiency of two different silica nanostructures as release vehicles of Cisplatin are reported. The 1-hexadeciltrimethyl-ammonium bromide templating agent was used to obtain mesoporous silica nanoparticles which were later loaded with Cisplatin. While sol-gel silica was very fast prepared using an excess of acetic acid during the hydrolysis-condensation reactions of tetraethylorthosilicate and at the same time the Cisplatin was added. Several physicochemical techniques including spectroscopies, electronic microscopy, X-ray diffraction, N2 adsorption-desorption were used to characterise the silica nanostructures. An in vitro Cisplatin release test was carried out using artificial cerebrospinal fluid. Finally, the toxicity of all silica nanostructures was tested using the C6 cancer cell line. The spectroscopic results showed the suitable stabilisation of Cisplatin into the two different silica nanostructures. A large surface area was obtained for the mesoporous silica nanoparticles, while low areas were obtained in the silica nanoparticles. Cisplatin was released faster from mesoporous silica channels than from inside of aggregates nanoparticles silica. Cisplatin alone, as well as, cisplatin released from both silica nanostructures exerted a toxic effect on cancer cells. In contrast, both silica structures without the drug did not exert any toxic effect.


Assuntos
Neoplasias Encefálicas/metabolismo , Cisplatino , Portadores de Fármacos , Nanopartículas/química , Dióxido de Silício/química , Animais , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratos
6.
Cir Cir ; 87(3): 278-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135783

RESUMO

OBJECTIVE: To analyze the accuracy of endoscopic ultrasound (EUS) in the evaluation of ampullary tumors compared to histopathology (HP) staging. METHODS: A retrospective diagnostic test study. Patients with ampullary tumors staged by EUS and postpancreatoduodenectomy HP attended during 2012-2018 at tertiary level hospital. RESULTS: 14 patients with adenocarcinoma where included. Tumor size measured by EUS showed an adequate correlation (R = 0.65; p= 0.01) with HP. The accuracy in the evaluation of duodenal wall, pancreatic, and biliary duct invasion was 78.5, 78.5 and 57.1%, respectively. By HP, there were three T1 (21.4%), two T2 (14.2%) and nine T3 (64.2%). The accuracy of T and N staging by EUS was 71.4% (kappa = 0.50) and 50% (kappa = -0.04) respectively. There were more staging errors in patients with biliary stent. CONCLUSION: EUS was useful in estimating tumor size, duodenal wall and pancreatic invasion. Limitation was found in the evaluation of biliary duct invasion, as well as overestimation of T stage and underestimation of N stage. It is necessary an increased effort in ultrasonography training. We suggest EUS testing before biliary stenting.


OBJETIVO: Comparar el ultrasonido endoscópico (USE) en la valoración de los tumores ampulares primarios (TAp) con referencia al estudio histopatológico (HP). MÉTODO: Estudio retrospectivo prolectivo de pruebas diagnósticas en pacientes con TAp estadificados por USE y pancreatoduodenectomía con estudio HP, atendidos de 2012 a 2018 en un hospital de tercer nivel de atención. RESULTADOS: Fueron incluidos14 pacientes con adenocarcinoma. El tamaño del tumor medido por USE mostró una adecuada correlación (R = 0.65; p = 0.01) con el HP. La exactitud en la determinación de la invasión a la pared duodenal, el páncreas y el conducto biliar fue del 78.5, el 78.5 y el 57.1%, respectivamente. Por HP hubo tres T1 (21.4%), dos T2 (14.2%) y nueve T3 (64.2%). La exactitud del estadiaje T y N por USE fue del 71.4% (kappa = 0.50) y del 50% (kappa = −0.04), respectivamente. Los errores en la estadificación fueron más frecuentes en los pacientes con prótesis biliar. CONCLUSIÓN: El USE mostró utilidad en la determinación del tamaño tumoral y de la invasión al duodeno y al páncreas, y más limitada en la determinación de la invasión al conducto biliar por presencia de prótesis. Se observa una sobreestimación del estadiaje T y una subestimación del N. Es necesario mayor capacitación y sugerimos realizarse antes de colocar una prótesis biliar.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/patologia , Endoscopia do Sistema Digestório , Endossonografia , Cuidados Pré-Operatórios , Neoplasias do Ducto Colédoco/diagnóstico por imagem , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos
7.
Bol. latinoam. Caribe plantas med. aromát ; 17(4)jul. 2018. tab, ilus, graf
Artigo em Inglês | LILACS | ID: biblio-915429

RESUMO

Lippia graveolens Kunth (Verbenaceae) is an economically important shrub known in Mexico as Oregano. In this work, the biocidal effect of the hexane extract of L. graveolens leaves was evaluated on two crop pests. Thus, larvae of Spodoptera frugiperda were fed with mixtures of extract and artificial diet. The nematicidal activity was evaluated on juveniles of Meloydogine javanica. Regarding S. frugiperda, quantitative differences between treatments and control were observed in dead pupae, surviving adults, and deformed adults (P < 0.05). All the surviving adults from the extract treatments were deformed. Nematicidal effect was registered, the LC50 and LC90 were 0.672 (0.654-0.690) and 0.965 (0.937-0.998) mg/mL respectively. The extract was characterized by NMR and GC-MS, being thymol the most abundant component (70.6%) in addition to carvacrol (22.8%). The results suggest the consideration of the hexane extract of L. graveolens leaves within the alternatives for the biological control of pests.


Lippia graveolens Kunth (Verbenaceae) es un arbusto con importancia económica conocido en México como Orégano. En éste trabajo se evaluó el efecto biocida del extracto hexánico de hojas L. graveolens sobre dos plagas agrícolas. Así, larvas de S. frugiperda fueron alimentadas con mezclas de dieta artificial y extracto. La actividad nematicida fue evaluada en juveniles de Meloydogine javanica, Respecto a S. frugiperda, se observaron diferencias cuantitativas entre tratamiento y control en cuanto a pupas muertas, adultos sobrevivientes y adultos deformes (P < 0.05). Todos los adultos provenientes de tratamientos con extracto estuvieron malformados. Hubo efecto nematicida, calculándose CL50 y CL90 de 0.672 (0.654-0.690) y 0.965 (0.937-0.998) mg/mL respectivamente. El extracto se caracterizó por RMN y CG-EM. Los compuestos más abundantes fueron timol (70.6%), ademas del carvacrol (22.8%). Los resultados sugieren considerar al extracto hexánico de hojas de L. graveolens dentro de las alternativas para el control biológico de plagas.


Assuntos
Extratos Vegetais/farmacologia , Spodoptera/efeitos dos fármacos , Folhas de Planta/química , Lippia/química , Antinematódeos/farmacologia , Fenóis/análise , Extratos Vegetais/química , Espectroscopia de Ressonância Magnética , Controle Biológico de Vetores , Cromatografia Gasosa/métodos , Verbenaceae , Monoterpenos/análise , Larva , Antinematódeos/química
8.
Biomed Res Int ; 2017: 3507671, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28685147

RESUMO

Prostate cancer (PC) is the second most commonly diagnosed type of cancer in males with 1,114,072 new cases in 2015. The MTHFR enzyme acts in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. MTHFR C677T alters homocysteine levels and folate assimilation associated with DNA damage. Androgens play essential roles in prostate growth. The SRD5A2 enzyme metabolizes testosterone and the V89L polymorphism reduces in vivo SRD5A2 activity. The androgen receptor gene codes for a three-domain protein that contains two polymorphic trinucleotide repeats (CAG, GGC). Therefore, it is essential to know how PC risk is associated with clinical features and polymorphisms in high altitude Ecuadorian mestizo populations. We analyzed 480 healthy and 326 affected men from our three retrospective case-control studies. We found significant association between MTHFR C/T (odds ratio [OR] = 2.2; P = 0.009), MTHFR C/T+T/T (OR = 2.22; P = 0.009), and PC. The SRD5A2 A49T substitution was associated with higher pTNM stage (OR = 2.88; P = 0.039) and elevated Gleason grade (OR = 3.15; P = 0.004). Additionally, patients with ≤21 CAG repeats have an increased risk of developing PC (OR = 2.99; P < 0.001). In conclusion, genotype polymorphism studies are important to characterize genetic variations in high altitude mestizo populations.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Proteínas de Membrana/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Proteínas de Neoplasias/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Alelos , Equador/epidemiologia , Equador/etnologia , Humanos , Indígenas Sul-Americanos/etnologia , Indígenas Sul-Americanos/genética , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etnologia
10.
Clin Nutr ; 33(6): 1017-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24746976

RESUMO

BACKGROUND: Nutritional interventions have shown increased energy intake but not improvement in health-related quality of life (HRQL) or prognosis in non small cell lung cancer (NSCLC) patients. Eicosapentaenoic acid has been proposed to have anti-inflammatory, anticachectic and antitumoural effects. OBJECTIVE: To compare the effect of an oral EPA enriched supplement with an isocaloric diet on nutritional, clinical and inflammatory parameters and HRQL in advanced NSCLC patients. DESIGN: Patients with advanced NSCLC were randomized to receive diet plus oral nutritional supplement containing EPA (ONS-EPA) or only isocaloric diet (C). All patients received paclitaxel and cisplatin/carboplatin treatment. Weight, body composition, dietary intake, inflammatory parameters and HRQL were assessed at baseline and after the first and second cycles of chemotherapy. Response to chemotherapy and survival were evaluated. RESULTS: Ninety two patients were analysed (46 ONS-EPA,46 C). ONS-EPA group had significantly greater energy (p < 0.001) and protein (p < 0.001) intake compared with control. Compared with baseline, patients receiving the ONS-EPA gained 1.6 ± 5 kg of lean body mass (LBM) compared with a loss of -2.0 ± 6 kg in the control (p = 0.01). Fatigue, loss of appetite and neuropathy decreased in the ONS-EPA group (p ≤ 0.05). There was no difference in response rate or overall survival between groups. CONCLUSION: Patients with NSCLC receiving ONS-EPA significantly improves energy and protein intake, body composition. and decreased fatigue, loss of appetite and neuropathy. Registered with ClinicalTrials.gov (NCT01048970).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Suplementos Nutricionais , Ácido Eicosapentaenoico/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apetite/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
11.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1052775

RESUMO

Objetivo: Estimar la Prevalencia de sobrepeso y Obesidad en la población infantil de 5 a 11 años de la I.E. Regulo Guevara del caserío de Santa Clara. Material y métodos: El estudio fue de naturaleza descriptivo-transversal; se realizó en la jurisdicción del Puesto de Salud "Santa Clara" del caserío Santa Clara, Distrito de Pitipo, Provincia de Ferreñafe; Departamento de Lambayeque. La muestra estuvo formada por la totalidad de alumnos de 5 a 11 años que asciende a 151, a los cuales se les peso y tallo, para calcular el IMC, el cual sirvió para la valoración nutricional. Para el procesamiento de la muestra se utilizó el Excel versión 2010. Resultados: En los resultados se evidenció que La prevalencia de sobrepeso y obesidad fue de 14% y 6% respectivamente; además con respecto a la edad, existe prevalencia de sobrepeso y obesidad en la edad de 9 años, con 29% y 33% respecto a las demás edades de la infancia. De acuerdo al sexo existe prevalencia de sobrepeso en el sexo masculino con 57% y prevalencia de obesidad en el sexo femenino con 67%. Conclusiones: Teniendo en cuenta la edad para el sexo masculino, existe prevalencia de sobrepeso y obesidad en niños a las edades de 6 y 8 años respectivamente. Y respecto a la edad para el sexo femenino existe prevalencia de sobrepeso y obesidad en las niñas a los 9 años. Finalmente la valoración nutricional de la población infantil de 5 a 11 años de la I.E. Regulo Guevara del caserío (área urbano marginal-rural) de Santa Clara fue de sobrepeso 14%, obesidad 6% y desnutrición 0.7% representada por un solo caso, lo que nos lleva a evidenciar que el problema nutricional emergente en nuestra población ya no es la desnutrición sino el sobrepeso y la obesidad, al igual que en las poblaciones de la zona urbana como lo mencionan otros estudios en poblaciones de área urbana de Chiclayo.(AU)

12.
Int J Nanomedicine ; 8: 581-92, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23413123

RESUMO

The anticancer properties of pure copper (II) acetate and copper (II) acetylacetonate, alone and loaded on functionalized sol-gel titania (TiO(2)), were determined in four different cancer cell lines (C6, RG2, B16, and U373), using increasing concentrations of these compounds. The copper complexes were loaded onto the TiO(2) network during its preparation by the solgel process. Once copper-TiO(2) materials were obtained, these were characterized by several physical-chemical techniques. An in vitro copper complex-release test was developed in an aqueous medium at room temperature and monitored by ultraviolet spectroscopy. The toxic effect of the copper complexes, alone and loaded on TiO(2), was determined using a cell viability 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, when cancer cells were treated with increasing concentrations (15.75-1000 mg/mL) of these. Characterization studies revealed that the addition of copper complexes to the TiO(2) sol-gel network during its preparation, did not generate changes in the molecular structure of the complexes. The surface area, pore volume, and pore diameter were affected by the copper complex additions and by the crystalline phases obtained. The kinetic profiles of both copper complexes released indicated two different stages of release: The first one was governed by first-order kinetics and the second was governed by zero-order kinetics. The cell viability assay revealed a cytotoxic effect of copper complexes, copper-TiO(2), and cisplatin in a dose-dependent response for all the cell lines; however, the copper complexes exhibited a better cytotoxic effect than the cisplatin compound. TiO(2) alone presented a minor cytotoxicity for C6 and B16 cells; however, it did not cause any toxic effect on the RG2 and U373 cells, which indicates its high biocompatibility with these cells.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Cobre/química , Nanopartículas/química , Titânio/química , Adsorção , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Relação Dose-Resposta a Droga , Humanos , Cinética , Camundongos , Microscopia Eletrônica de Transmissão , Nanomedicina , Nanopartículas/administração & dosagem , Tamanho da Partícula , Ratos , Titânio/farmacologia
13.
PLoS One ; 8(1): e51587, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23335954

RESUMO

Epigenetic modifications play a central role in the differentiation and function of immune cells in adult animals. Developmentally regulated epigenetic patterns also appear to contribute to the ontogeny of the immune system. We show here that the epigenetic profile of the T-helper (Th) 2 locus undergoes changes in T lineage cells beginning in mid-gestation and extending throughout the first week of life. In particular, regulatory regions of the Th2 locus are largely methylated at CpG residues among fetal liver common lymphoid progenitor cells. The locus subsequently becomes highly hypomethylated among the downstream progeny of these cells within the fetal thymus. This hypomethylated state is preserved until birth when the locus becomes rapidly re-methylated, achieving adult-like status by 3-6 days post birth. Notably, the capacity for rapid, high level Th2 cytokine production is lost in parallel with this re-methylation. In vitro organ culture and in vivo transplantation experiments indicate that signals from the adult environment are required to achieve the postnatal methylated state. Together, these findings indicate that the Th2 bias of neonates may be conferred, in part, by an epigenetic profile inherited from fetal life. However, the fetal program is rapidly terminated post birth by the development of signals leading to the acquisition of adult-like epigenetic patterns.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Células Th2/metabolismo , Timo/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linhagem da Célula/genética , Citocinas/biossíntese , Metilação de DNA , Meio Ambiente , Feminino , Ordem dos Genes , Interação Gene-Ambiente , Loci Gênicos , Histonas/metabolismo , Células Progenitoras Linfoides/metabolismo , Camundongos , Camundongos Transgênicos , Sequências Reguladoras de Ácido Nucleico , Células Th2/imunologia , Timócitos/imunologia , Timócitos/metabolismo , Timo/embriologia , Timo/imunologia , Transcrição Gênica
14.
Exp Neurol ; 236(1): 131-40, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22542948

RESUMO

Lafora disease (LD) is an autosomal recessive, always fatal progressive myoclonus epilepsy with rapid cognitive and neurologic deterioration. One of the pathological hallmarks of LD is the presence of cytoplasmic PAS+polyglucosan inclusions called Lafora bodies (LBs). Current clinical and neuropathological views consider LBs to be the cause of neurological derangement of patients. A systematic study of the ontogeny and structural features of the LBs has not been done in the past. Therefore, we undertook a detailed microscopic analysis of the neuropile of a Laforin-deficient (epm2a-/-) mouse model. Wild type and epm2a-/- mice were sacrificed at different ages and their encephalon processed for light microscopy. Luxol-fast-blue, PAS, Bielschowski techniques, as well as immunocytochemistry (TUNEL, Caspase-3, Apaf-1, Cytochrome-C and Neurofilament L antibodies) were used. Young null mice (11 days old) showed necrotic neuronal death in the absence of LBs. Both cell death and LBs showed a progressive increment in size and number with age. Type I LBs emerged at two weeks of age and were distributed in somata and neurites. Type II LBs appeared around the second month of age and always showed a complex architecture and restricted to neuronal somata. Their number was considerably less than type I LBs. Bielschowski method showed neurofibrillary degeneration and senile-like plaques. These changes were more prominent in the hippocampus and ventral pons. Neurofibrillary tangles were already present in 11 days-old experimental animals, whereas senile-like plaques appeared around the third to fourth month of life. The encephalon of null mice was not uniformly affected: Diencephalic structures were spared, whereas cerebral cortex, basal ganglia, pons, hippocampus and cerebellum were notoriously affected. This uneven distribution was present even within the same structure, i.e., hippocampal sectors. Of special relevance, was the observation of the presence of immunoreactivity to neurofilament L on the external rim of type II LBs. Perhaps, type II LB is not the end point of a metabolic abnormality. Instead, we suggest that type II LB is a highly specialized structural and functional entity that emerges as a neuronal response to major carbohydrate metabolism impairment. Early necrotic cell death, neurocytoskeleton derangement, different structural and probably functional profiles for both forms of LBs, a potential relationship between the external rim of the LB type II and the cytoskeleton and an uneven distribution of these abnormalities indicate that LD is both a complex neurodegenerative disease and a glycogen metabolism disorder. Our findings are critical for future studies on disease mechanisms and therapies for LD. Interestingly, the neurodegenerative changes observed in this LD model can also be useful for understanding the process of dementia.


Assuntos
Citoesqueleto/patologia , Fosfatases de Especificidade Dupla/genética , Doença de Lafora/genética , Doença de Lafora/patologia , Degeneração Neural/patologia , Neurônios/patologia , Animais , Gânglios da Base/patologia , Tronco Encefálico/patologia , Citoplasma/patologia , Modelos Animais de Doenças , Feminino , Hipocampo/patologia , Doença de Lafora/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Degeneração Neural/genética , Degeneração Neural/metabolismo , Emaranhados Neurofibrilares/patologia , Neurópilo/patologia , Fenótipo , Placa Amiloide/patologia , Proteínas Tirosina Fosfatases não Receptoras , Área Tegmentar Ventral/patologia
15.
Nutr Cancer ; 64(4): 526-34, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489794

RESUMO

Early identification and treatment of nutritional deficiencies can lead to improved outcomes in the quality of life (QoL) and survival of patients with nonsmall cell lung cancer (NSCLC). Noninvasive techniques are needed to evaluate changes in body composition as part of determining nutritional status. The aim of the study was to evaluate the association of nutritional parameters in health-related quality of life (HRQL) and survival in patients with advanced NSCLC. Chemotherapy-naïve patients with advanced NSCLC with good performance status Eastern Cooperative Oncology Group (ECOG) 0-2 were included prospectively in the study. We evaluated inflammatory parameters such as C-reactive protein, platelet/lymphocyte index, neutrophil/lymphocyte index, serum interleukin (IL)-6, and tumor necrosis factor-α, and nutritional variables such as body mass index (BMI) and serum albumin levels. Bioelectrical impedance analysis including phase angle was obtained before cisplatin-based chemotherapy was started. HRQL was assessed by application of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13 instruments at baseline. Overall survival (OS) was calculated with the Kaplan-Meier method and analyzed with log-rank and Cox proportional hazard models. One hundred nineteen patients were included. Mean BMI was 24.8 ± 4.5 kg/m(2), average weight loss of patients was 8.4%, and median phase angle was 5.8°. Malnutrition measured by subjective global assessment (SGA), weight loss >10%, BMI >20 was associated with lower HRQL scales. Patients with ECOG 2, high content serum IL-6, lower phase angle, and malnutrition parameters showed lower OS; however, after multivariate analysis, only ECOG 2 [Hazard ratio (HR), 2.7; 95% confidence interval (95% CI), 1.5-4.7; P = 0.001], phase angle ≤5.8° (HR = 3.02; 95% CI: 1.2-7.11; P = 0.011), and SGA (HR = 2.7; 95% CI, 1.31-5.5; P = 0.005) were associated with poor survival. Patients were divided into low-, intermediate-, and high-risk groups according to regression coefficients; OS at 1 yr was 78.4, 53, and 13.8%, respectively. Malnutrition is associated with low HRQL and is an independent prognostic factor in advanced NSCLC. The results warrant prospective trials to evaluate the impact of different nutritional interventions on HRQL and survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Impedância Elétrica/uso terapêutico , Inflamação/fisiopatologia , Estado Nutricional , Qualidade de Vida , Idoso , Proteína C-Reativa/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Masculino , Desnutrição/fisiopatologia , Desnutrição/prevenção & controle , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/sangue
16.
J Neurooncol ; 98(3): 379-84, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20013146

RESUMO

Meningiomas are benign tumors, with low rate of recurrence after surgery. The most important factor predicting recurrence is the extent of surgical resection; other factors have been studied with conflicting results. Angiogenesis, an important substratum for growth and spread of neoplasic cells, and the expression of estrogen and progesterone receptors (ER, PR), could play a role in the recurrence of meningioma. We evaluated 42 patients with meningioma diagnosis (confirmed by histopathology) treated exclusively by surgery between January 1995 and December 1999, and compared the recurring and non-recurring groups after a ten-year follow-up period. Recurrence was associated with several factors including vascular density (VD), cell proliferation index (CPI), ER, PR, and cyclin E (CE) tissue expression, as evaluated by immunohistochemistry. Complete surgical resection was achieved in 41% of patients. Recurrence of meningioma was found in 17 patients (40%). Median + or - standard deviation (SD) of recurrence time was 32 + or - 5 months. When recurrence versus no recurrence was compared, mean + or - SD of VD and CPI were 9 + or - 3.6 and 607.6 + or - 233 (40x/10 fields) respectively. Tissue expression was positive for ER, PR, and CE in 28, 62 and 91% of patients, respectively. The sole significant recurrence-associated factors were extent of resection (P = 0.003) and VD (P = 0.004). ER, PR, and CE-tissue expression were not statistically significant. The most important factor associated with meningioma relapse was vascular density, independently of hormonal status and extent of surgical resection. Patients with a high risk of recurrence could benefit from additional treatment.


Assuntos
Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Neovascularização Patológica/etiologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Ciclina E/metabolismo , Feminino , Humanos , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/patologia , Meningioma/complicações , Meningioma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Eur J Immunol ; 36(5): 1241-53, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16568497

RESUMO

Murine neonatal immunity is typically Th2 biased. This is characterized by high-level IL-4 production at all phases of the immune response and poor IFN-gamma memory responses. The differential expression of Th1/Th2 cytokines by neonates and adults could arise if the critical regulators of Th differentiation and function, STAT6 and T-bet, operate differently during the neonatal period. To test this idea, the Th cell responses of wild-type, T-bet-deficient, or STAT6-deficient mice were compared in vitro and in vivo. The absence of these factors had similar qualitative effects on the development of effector function in neonates and adults, i.e., if a Th lineage was inhibited or enhanced in adult animals, a similar phenomenon was observed in neonates. However, there was a striking difference observed in the in vivo Th1 memory responses of STAT6-deficient mice initially immunized as neonates. Antigen-specific IFN-gamma production was increased 50-100-fold in STAT6-deficient neonates, achieving levels similar to those of STAT6-deficient adults. These findings demonstrate that STAT6 and T-bet signals are central in shaping Th responses in wild-type neonates, as in adult mice, and that the master regulators of Th cell development and function are already firmly established in early life.


Assuntos
Fator de Transcrição STAT6/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Fatores de Transcrição/fisiologia , Animais , Animais Recém-Nascidos , Apoptose , Fator de Transcrição GATA3/fisiologia , Memória Imunológica , Interleucina-4/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Proteínas com Domínio T , Células Th1/imunologia , Células Th2/imunologia
19.
Clin Invest Med ; 28(1): 23-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15770879

RESUMO

INTRODUCTION: TNFalpha, a proinflammatory cytokine expressed under several conditions in the myocardium, may contribute to myocardial damage in heart failure (HF). The aim of the study was to determine TNFalpha concentrations and their relation to severity, mortality, and clinical, biochemical and echocardiographic parameters in patients with stable chronic heart failure. PATIENTS AND METHODS: In a prospective study in 128 patients with HF, average follow-up 33 mos, serum concenrations of TNFalpha were determined, and clinical, biochemical and echocardiographic characteristics and mortality were recorded. Serum TNFalpha concentrations were also determined in 35 healthy subjects. Univariate and multivariate analyses were performed to determine variables that could influence TNFalpha concentrations, and that could predict mortality. RESULTS: Patients with HF have higher serum concentrations of TNFalpha than controls (6.72+/-0.2 vs 5.5+/-0.2 pg/ml, P=0.02). Patients with functional class I had lower concenrations of TNFalpha than patients with functional classes II and III (P=0.05 and P=0.001, respectively). Variables associated with higher concentrations of TNFalpha were; lower ejection fraction (P=0.04), worse functional class (P=0.007), coronary artery disease (P=0.05), chronic renal failure (P=0.02), arterial hypertension (P=0.05), higher concentrations of epinephrine (P=0.03) and norepinephrine (P=0.05). On follow-up, factors associated with decline in ejection fraction were arterial hypertension and higher total catecholamines. Factors associated with higher mortality were hypertension, elevated concentrations of TNFalpha and troponin T. Endothelin levels correlated with worsening functional class. CONCLUSION: Serum TNFalpha and troponin T concentrations are independent predictors of severity and mortality in stable HF patients.


Assuntos
Biomarcadores , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Troponina T/sangue , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Idoso , Catecolaminas/metabolismo , Citocinas/metabolismo , Ecocardiografia , Endotelinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Epinefrina/metabolismo , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Miocárdio/patologia , Norepinefrina/metabolismo , Prognóstico , Estudos Prospectivos , Fatores de Tempo
20.
Med. interna (Caracas) ; 21(1): 4-32, 2005. tab
Artigo em Espanhol | LILACS | ID: lil-477365

RESUMO

La vacunación no recibe la misma prioridad que la del niño. Existe una falta de conocimiento en el personal médico e insuficiente cultura en la población. Hay varias razones para vacunar al adulto: exposición a riesgos diferentes que el menor, como laborales y los que derivan de la actividad sexual e inmunidad no permanente. El esquema de vacunación del adulto tiene diferentes escenarios: adulto sano y con patologías de base, embarazada, adultos con inmunodeficiencias, personal de salud, viajeros e inmigrantes. Para cada uno de estos grupos, se deben conocer factores de riesgo y antecedentes que contraindiquen el uso de cualquier vacuna, así como indicaciones de profilaxis y preexposición. Es importante, además, el conocimiento sobre los tipos de vacuna, interferencia entre ellas o con el uso de inmunoglobulinas y antimicrobianos.


Assuntos
Humanos , Masculino , Adulto , Feminino , Antibioticoprofilaxia , Vacinas/administração & dosagem , Vacinas/imunologia , Medicina Interna , Venezuela
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