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1.
Stem Cells Transl Med ; 13(3): 193-203, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366909

RESUMO

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Animais , Humanos , Camundongos , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Resultado do Tratamento , Cordão Umbilical
2.
J Cancer Res Clin Oncol ; 149(19): 17335-17346, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37831273

RESUMO

PURPOSE: The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. METHODS: A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. RESULTS: The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. CONCLUSIONS: The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Maraviroc/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Linhagem Celular Tumoral , Neoplasias Bucais/tratamento farmacológico , RNA Interferente Pequeno/metabolismo , Microambiente Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo
3.
Front Immunol ; 12: 768771, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790203

RESUMO

Osteoarticular diseases (OD), such as rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic autoimmune/inflammatory and age-related diseases that affect the joints and other organs for which the current therapies are not effective. Cell therapy using mesenchymal stem/stromal cells (MSCs) is an alternative treatment due to their immunomodulatory and tissue differentiation capacity. Several experimental studies in numerous diseases have demonstrated the MSCs' therapeutic effects. However, MSCs have shown heterogeneity, instability of stemness and differentiation capacities, limited homing ability, and various adverse responses such as abnormal differentiation and tumor formation. Recently, acellular therapy based on MSC secreted factors has raised the attention of several studies. It has been shown that molecules embedded in extracellular vesicles (EVs) derived from MSCs, particularly those from the small fraction enriched in exosomes (sEVs), effectively mimic their impact in target cells. The biological effects of sEVs critically depend on their cargo, where sEVs-embedded microRNAs (miRNAs) are particularly relevant due to their crucial role in gene expression regulation. Therefore, in this review, we will focus on the effect of sEVs derived from MSCs and their miRNA cargo on target cells associated with the pathology of RA and OA and their potential therapeutic impact.


Assuntos
Artrite Reumatoide/terapia , Vesículas Extracelulares/fisiologia , Transplante de Células-Tronco Mesenquimais , MicroRNAs/fisiologia , Osteoartrite/terapia , Artrite Reumatoide/etiologia , Humanos , Osteoartrite/etiologia , Fator de Crescimento Transformador beta/fisiologia
4.
Front Immunol ; 12: 624746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149687

RESUMO

Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage's metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC's therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.


Assuntos
Comunicação Celular , Plasticidade Celular , Reprogramação Celular , Metabolismo Energético , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Microambiente Celular , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Células-Tronco Mesenquimais/imunologia , Fenótipo , Transdução de Sinais
5.
Archiv. med. fam. gen. (En línea) ; 18(1): 30-40, mar. 2021. tab, graf
Artigo em Espanhol | LILACS, InstitutionalDB, BINACIS, UNISALUD | ID: biblio-1292836

RESUMO

Introducción: la comunicación es trascendental para la vida en sociedad. El éxito de cualquier entrevista clínica depende de la calidad de la comunicación entre el médico y el paciente. Distintos factores pueden interferir en esta, como el ambiente, el tiempo y las interrupciones. Objetivo: Evaluar el grado de comprensión del mensaje transmitido por el médico hacia el paciente. Material y método: Trabajo multicéntrico, cualitativo cuantitativo. Componente cuantitativo: descriptivo de corte transversal de abril a julio de 2014. Se incluyeron 1200 adultos de ambos sexos, que asistieron a los Ce.M.A.P y 40 médicos de familia. Componente cualitativo: Muestreo no probabilístico, intencional, hasta saturación de datos. Triangulación y convergencia de datos. Resultados y discusión: Respecto al componente cuantitativo, se encontró que nuestras hipótesis acerca de la falta de comprensión del mensaje (indicaciones y problema de salud) no pudieron comprobarse. Ya que las indicaciones realizadas por el médico tuvieron una adecuación total del 60% y comprendieron el problema de salud un 77% de los pacientes entrevistados. Para el componente cualitativo luego del análisis temático se obtuvieron barreras (tiempo, paciente polidemandante, ideas previas, omisión de indicaciones no farmacológicas) y facilitadores (conocimiento previo del problema de salud, longitudinalidad, paciente acompañado) para la comprensión del mensaje. Conclusiones: Los pacientes entienden el mensaje de sus médicos de familia, ya que contamos con herramientas concretas como la escucha empática, el proceso clínico centrado en la persona y la longitudinalidad en la atención (AU)


Introduction: communication is important for life in a society. Success in any clinical interview depends on the quality of patient-doctor communication. Different factors may interfere, like the environment, time and interruptions. Objective: Asses the level of understanding of the message given to the patient by the doctor. Material and method: Multicenter research trial, qualitative and quantitative. Quantitative component: cross sectional descriptive from April to June 2014. 1200 adults of both sexes who assisted to the primary health care center: "Ce.M.A.P." in the City of Buenos Aires, Rosario and Tucumán and 40 family practitioners. Qualitative component: nonprobability, intentional sampling upon data saturation. Data triangulation and convergence. Results and discussion: as regards the quantitative component, we found out that our hypothesis in relation to the lack of understanding in the message (indications and health problem) could not be proven. Since 60% of the practitioner's indications were followed and 77% of the interviewed patients understood the health problem. Considering the qualitative component after the thematic analysis, barriers (time, highly demanding patient, previous knowledge, omission of non-pharmacological indications) and facilitators were obtained (previous knowledge of health problem, longitudinality, accompanied patient) to understand the message. Conclusion: patients understand their family practitioner's message since we have specific tools like empathic listening, patient centered healthcare and longitudinality in attention (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Relações Médico-Paciente , Comunicação em Saúde , Entrevista
6.
Sci Total Environ ; 657: 1535-1542, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30677919

RESUMO

Spilled oil treated with Corexit dispersant can cause unintended impacts on marine environment systems including altering marine organic matter dynamics; however, impacts on microgels and marine oil snow (MOS) formation are still debated and remain to be fully understood. Extracellular polymeric substances (EPS) are a major source of marine organic carbon for MOS and microgel formation. EPS initial aggregation plays key roles in the oil degrading process and various biogeochemical reactions. Here we used four types of EPS with water accommodated fraction (WAF), chemically-enhanced WAF (CEWAF) and Corexit, to represent potential situations during oil spills and post-application of Corexit. We found that Corexit alone can inhibit EPS aggregation and disperse pre-existing microgels. CEWAF can enhance EPS aggregation with efficiency by up to 80%-100% and more aggregates accumulated within the air-water interface. Additionally, more hydrophobic EPS aggregates showed high resistance to Corexit dispersion while hydrophilic EPS were more sensitive. Effects of oil spills on marine gel particle formation are primarily determined by chemical characteristics (hydrophobicity and protein content) of the constituent EPS. This study offers unique insights for organic particle dynamics and identifies controlling factors for MOS or gel particles associated with oil spills and Corexit dispersant used.


Assuntos
Meio Ambiente , Recuperação e Remediação Ambiental/métodos , Matriz Extracelular de Substâncias Poliméricas/química , Poluição por Petróleo , Petróleo , Organismos Aquáticos/metabolismo , Fitoplâncton/metabolismo , Tensoativos/química
7.
Rev. mex. trastor. aliment ; 9(2): 250-263, jul.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-978741

RESUMO

Resumen La alimentación de los niños durante el horario escolar es fundamental, por lo que a fin de adecuar la oferta alimentaria, es indispensable conocer cuáles son las preferencias alimentarias del alumnado. Así, el propósito de este estudio fue identificar los motivos de las preferencias y el consumo de alimentos durante el recreo escolar. Participaron 38 niños de 9-10 años de edad (55% niñas y 45% niños), alumnos de una escuela primaria pública de tiempo completo. Este estudio etnográfico comprendió el registro de alimentos consumidos y preferidos habitualmente, así como las narrativas de los niños, a través de observación dirigida, entrevistas no estructuradas y elaboración de dibujos. Se encontró que las preferencias alimentarias de los niños están estrechamente vinculadas al contexto familiar y los sentimientos ligados a éste. No obstante, en dichas preferencias influyen también la educación alimentaria recibida (escolar y extra-escolar), así como la disponibilidad-restricción de alimentos dentro de la escuela. En conclusión, aunque las y los niños podían no consumir en el recreo escolar su alimento favorito, adaptaban sus preferencias en función de los alimentos disponibles en la escuela, de modo que la selección variaba en función de la percepción y ponderación de las propiedades organolépticas del alimento (e.g., sabor, consistencia, temperatura).


Abstract Feeding children during school hours is essential, so to adapt the food supply, it is necessary to know what students' food preferences are. Thus, the purpose of this study was to identify the reasons for preferences and food consumption during school breaks. Thirty-eight children with an age range of 9 to 10 years (55% girls and 45% boys), from a full-time public primary school participated. This ethnographic study comprised the recording of commonly consumed and preferred foods, as well as children's narratives, through directed observation, unstructured interviews and drawings. It was found that children's food preferences are closely linked to the family context and the feelings linked to them. However, these preferences also influence the food education received (school and extra-school), as well as the availability-restriction of food within the school. In conclusion, although children could not consume their favorite food at school, they adapted their preferences according to the foods available at school, so the selection varied based on the perception and weighting of the organoleptic properties of the food (e.g., taste, consistency, temperature).

8.
Molecules ; 21(10)2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27739411

RESUMO

Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K⁺-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Contração Muscular/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/farmacologia , Talidomida/análogos & derivados , Adolescente , Adulto , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/química , Células Cultivadas , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Feminino , Células HeLa , Humanos , Modelos Biológicos , Miométrio/citologia , Miométrio/metabolismo , Inibidores da Fosfodiesterase 4/química , Potássio/farmacologia , Gravidez , Rolipram/farmacologia , Adulto Jovem
9.
Appl Environ Microbiol ; 81(6): 2050-62, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25576613

RESUMO

Recently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili.


Assuntos
Aderência Bacteriana , Citocinas/metabolismo , Fímbrias Bacterianas/imunologia , Lacticaseibacillus rhamnosus/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Fagocitose , Animais , Linhagem Celular , Tolerância Imunológica , Lacticaseibacillus rhamnosus/fisiologia , Camundongos
10.
Scientifica (Cairo) ; 2014: 915725, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25243094

RESUMO

Development is a tightly regulated process that involves stem cell self-renewal, differentiation, cell-to-cell communication, apoptosis, and blood vessel formation. These coordinated processes ensure that tissues maintain a size and architecture that is appropriate for normal tissue function. As such, tumors arise when cells acquire genetic mutations that allow them to escape the normal growth constraints. In this regard, the study of tumor predisposition syndromes affords a unique platform to better understand normal development and the process by which normal cells transform into cancers. Herein, we review the processes governing normal brain development, discuss how brain cancer represents a disruption of these normal processes, and highlight insights into both normal development and cancer made possible by the study of tumor predisposition syndromes.

11.
PLoS One ; 9(5): e97320, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24817309

RESUMO

OBJECTIVE: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). METHODS: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. RESULTS: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. SIGNIFICANCE: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma.


Assuntos
Ependimoma/fisiopatologia , Células-Tronco Neurais/fisiologia , Neurofibromina 2/metabolismo , Neuropeptídeos/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Medula Espinal/fisiopatologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Western Blotting , Diferenciação Celular/fisiologia , Fracionamento Celular , Membrana Celular/metabolismo , Ependimoma/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/fisiologia , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Células-Tronco Neurais/metabolismo , Neurofibromina 2/genética , Neoplasias da Medula Espinal/tratamento farmacológico
12.
PeerJ ; 2: e309, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24688883

RESUMO

Background. Pacifier use decreases the risk of sudden infant death syndrome (SIDS). An emergency department (ED) visit may provide an opportunistic 'teachable moment' for parents. Objectives. To test the hypotheses (1) that caregivers were less familiar with the role of pacifiers in sudden infant death (SIDS) prevention than other recommendations, and (2) that an ED educational intervention would increase pacifier use in infants younger than six months, and (3) that otitis media would not occur more frequently in pacifier users. Methods. We did an intervention-group-only longitudinal study in a county hospital ED. We measured pacifier use infants and baseline knowledge of SIDs prevention recommendations in caregivers. We followed up three months later to determine pacifier use, and 12 months later to determine episodes of otitis media. Results. We analyzed data for 780 infants. Parents knew of advice against co-sleeping in 469/780 (60%), smoking in 660/776 (85%), and prone sleeping in 613/780 (79%). Only 268/777 (35%) knew the recommendation to offer a pacifier at bedtime. At enrollment 449/780 (58%) did not use a pacifier. Of 210/338 infants aged less than 6 months followed up 41/112 (37%) non-users had started using a pacifier at bedtime (NNT 3). Over the same period, 37/98 (38%) users had discontinued their pacifier. Otitis media did not differ between users and non-users at 12 months. Conclusion. Caregiver knowledge of the role of pacifiers in SIDS prevention was less than for other recommendations. Our educational intervention appeared to increase pacifier use. Pacifier use was not associated with increased otitis media.

13.
Cad. saúde colet., (Rio J.) ; 22(1): 69-74, Jan-Mar/2014. tab, graf
Artigo em Português | LILACS | ID: lil-709574

RESUMO

Este estudo objetivou identificar o perfil antropométrico e bioquímico e analisar a evolução do ganho de peso dos profissionais do Serviço de Nutrição e Dietética (SND) do Hospital de Clínicas de Porto Alegre (HCPA). Estudo de caráter longitudinal retrospectivo, com 190 funcionários. Aplicou-se questionário estruturado e foram realizadas análises bioquímicas e avaliação antropométrica. Observou-se excesso de peso em 60,8% dos funcionários. O ganho de peso encontrou-se associado ao tempo de serviço, turno de trabalho e prática de atividade física. O estudo demonstrou que 1 ano a mais de trabalho esteve associado ao ganho de peso médio de 500 g, o turno de trabalho com ganho de peso médio de 4 kg e a prática de atividade física com perda de peso médio de 3,3 kg. A associação entre ganho de peso, tempo e turno de trabalho em colaboradores de serviços de nutrição remete à necessidade de criação de programas de educação nutricional que promovam hábitos alimentares saudáveis.


This study aimed to identify anthropometric and biochemical status and to analyze the weight gain of collaborators of nutrition and dietetics services of Hospital de Clínicas de Porto Alegre (HCPA). This was a retrospective longitudinal study enrolled 190 employees. Nutritional assessment and clinical analysis was measurement. A structured questionnaire was applied all employees. The prevalence of excess weight was 60.8%. Weight gain was significantly associated to length of service, working shift and physical activity. The study showed that an additional year of work was associated with weight gain around 500 g, the shift in average gain of 4 kg and physical activity with average weight loss of 3.3 kg. The association between weight gain, working time and working shift in employees refers to the need to create nutrition intervention program aiming to promote healthy eating habits.

14.
Nat Neurosci ; 16(4): 426-33, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23455610

RESUMO

The autosomal dominant disorder neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome caused by inactivation of the NF2 tumor suppressor gene, encoding merlin. Apart from tumors affecting the peripheral and central nervous systems, most NF2 patients develop peripheral neuropathies. This peripheral nerve disease can occur in the absence of nerve-damaging tumors, suggesting an etiology that is independent of gross tumor burden. We discovered that merlin isoform 2 (merlin-iso2) has a specific function in maintaining axonal integrity and propose that reduced axonal NF2 gene dosage leads to NF2-associated polyneuropathy. We identified a merlin-iso2-dependent complex that promotes activation of the GTPase RhoA, enabling downstream Rho-associated kinase to promote neurofilament heavy chain phosphorylation. Merlin-iso2-deficient mice exhibited impaired locomotor capacities, delayed sensory reactions and electrophysiological signs of axonal neuropathy. Sciatic nerves from these mice and sural nerve biopsies from NF2 patients revealed reduced phosphorylation of the neurofilament H subunit, decreased interfilament spacings and irregularly shaped axons.


Assuntos
Neurofibromatose 2/metabolismo , Neurofibromina 2/fisiologia , Polineuropatias/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Neurofibromina 2/genética , Fosforilação/fisiologia , Polineuropatias/genética , Polineuropatias/patologia , Gravidez , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia
15.
Artigo em Português | LILACS | ID: biblio-834362

RESUMO

Introdução: Transtornos alimentares (TAs) são mais prevalentes em grupos específicos da população. Nutricionistas vem sendo identificados como grupo vulnerável a esses distúrbios. Objetivo: Avaliar prevalências de comportamentos alimentares inadequados (CAI) e níveis de insatisfação com imagem corporal (IIC) entre alunos de Nutrição da Universidade Federal do Rio Grande do Sul. Métodos: Foram convidados todos os alunos matriculados no curso. Utilizaram-se questionários auto-aplicáveis validados para avaliação de CAI (EAT-26) e IIC Body Shape Questionnaire (BSQ). O índice de massa corporal foi calculado a partir das medidas de peso e estatura. Calculadas médias, desvios-padrão e freqüências absolutas e relativas. Associações analisadas pelo teste do qui-quadrado, ao nível de P<0,05, utilizando-se do programa SPSS 13.0. Resultados: Foram estudados 104 alunos, com média etária de 22±4,5 anos e 96,2% do sexo feminino. As prevalências de CAI e de IIC foram de, respectivamente, 11,8% e 13,5%. Observada associação entre CAI e ICC nesta população (X2=22,85; P=0,000). Discussão: As prevalências de CAI e de IIC encontraram-se abaixo do esperado, sugerindo menor prevalência de comportamento característico de TA, comparadas a estudantes de Nutrição de outras Universidades. Entretanto, 92,8% das estudantes com IIC eram eutróficas, corroborando com a literatura: a insatisfação surge com a crença de “estar obeso”, apesar da eutrofia. Conclusão: Na população estudada há preocupação com o corpo, demonstrando a influência da pressão sociocultural nesse grupo, o que é preocupante, pois são futuros nutricionistas que influenciarão na construção de um ideal de corpo de seus pacientes reforçando ou não padrões de beleza impostos pela nossa sociedade.


Introduction: Eating disorders (EDs) are more prevalent in specific population groups. Nutritionists have been identified as a group vulnerable to these disorders. Aim: To assess the prevalence of inadequate eating behaviors (IEBs) and the levels of dissatisfaction with body image (DBI) among students of Nutrition from the Universidade Federal do Rio Grande do Sul. Methods: All students enrolled in the Nutrition major were invited to participate. Validated self-administered questionnaires were used to assess IEBs (Eating Attitude Test - EAT-26) and DBI (Body Shape Questionnaire - BSQ). Body mass index was calculated using height and weight data. We calculated means, standard deviations, and absolute and relative frequencies. The associations were analyzed by means of the chi-square test at a significance level of P<0.05 using the software SPSS 13.0. Results: One hundred and four students were investigated. Their mean age was 22±4.5 years and 96.2% of them were female. Prevalence rates of IEBs and DBI were, respectively, 11.8% and 13.5%. We found an association between IEBs and DBI in this population (X2=22.85; P=0.000). Discussion: The prevalence rates of IEBs and DBI were found to be lower than expected, suggesting a lower prevalence of the typical behavior of EDs compared with students of Nutrition from other universities. However, we found that 92.8% of the students showing DBI had normal weight, what corroborates with the literature: dissatisfaction is associated with the belief that “one is fat”, although their weight is normal. Conclusion: Our population sample is concerned with body shape, evidencing that there social and cultural influence on this group. This finding is a reason for concern because this is a group of future nutrition professionals who might influence their patients with regard to their perceptions of the ideal body, reinforcing or not the beauty standards imposed by our society.


Assuntos
Humanos , Comportamento Alimentar , Imagem Corporal , Transtornos da Alimentação e da Ingestão de Alimentos , Estudantes de Ciências da Saúde , Ciências da Nutrição
16.
Mol Vis ; 15: 2068-73, 2009 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-19862340

RESUMO

PURPOSE: The pterygium is characterized by a fibrovascular neoformation from the bulbar conjunctiva into the cornea. The recent discovery that abnormal markers associated with tumor diseases are identified in the pterygium strengthens the theory that the pterygium is a tumor-like disease rather than a degenerative disease. The CD30 molecule has been identified in neoplastic and normal epithelial proliferating cells. The aim of this study was to determine the expression of the CD30 molecule in the pterygium. METHODS: Immunohistochemical staining using an antibody to CD30 and to the Ki-67 nuclear antigen was performed on 25 pterygial specimens and 10 healthy conjunctivas. RESULTS: Strong immunostaining against CD30 was observed in all pterygium specimens, in contrast to the healthy conjunctivas that showed weak immono-positivity in only three cases. The staining was diffused, predominantly to the basal epithelium. The Ki-67 antigen was observed in the nucleus of the basal epithelium of the pterygial specimens, and no staining was observed in the healthy conjunctiva. When serial sections were stained with CD30 and Ki-67, the cells that expressed CD30 also expressed Ki-67. CONCLUSIONS: The present study identified for the first time the existence of CD30 molecules in the basal epithelium of a pterygium. The fact that the positivity to Ki-67 in the basal epithelium of the pterygium correlated with the CD30 reactivity suggested that this protein could be associated with the uncontrolled cell proliferation of the epithelium in this pathology. The CD30 molecule could therefore be a suitable target to be inhibited using chimerical antibodies in pterygium diseases.


Assuntos
Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Saúde , Antígeno Ki-1/metabolismo , Pterígio/metabolismo , Pterígio/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Coloração e Rotulagem
17.
Rev. salud pública ; 10(5): 818-830, nov.-dic. 2008. tab
Artigo em Espanhol | LILACS | ID: lil-511453

RESUMO

Objetivo La alta demanda para el tratamiento de la obesidad y la poca efectividad de las terapias convencionales favorecen el consumo de productos alternativos. Evaluar ensayos clínicos aleatorios sobre la pérdida de peso con los ingredientes de los productos alternativos de mayor consumo en México. Metodología Se realizó una encuesta para valorar la prevalencia de consumo de productos alternativos para la pérdida de peso en Ensenada, Baja California. Se investigaron los productos más vendidos y se obtuvieron los componentes activos. Se revisaron ensayos clínicos aleatorios registrados en Pubmed para los componentes activos mas utilizados. Se incluyeron y analizaron aquéllos que evaluaran cambios en el peso. Resultados Treinta y seis porciento de los encuestados han utilizado algún método alternativo para la pérdida de peso (83 por ciento mujeres). Los productos más referidos fueron licuados, tés, pastillas y linaza. Se encontraron 16 ensayos clínicos aleatorios de cuatro ingredientes: Garcinia Cambodia, té verde, L-carnitina y linaza. Solamente dos estudios demostraron una pérdida de peso significativa (2 5 por ciento) entre el grupo control y el experimental. En los estudios de L-Carnitina y linaza no se encontró una diferencia significativa. Conclusión Se concluye que no hay evidencias suficientes y de calidad que justifiquen la utilización de los productos alternativos para la pérdida de peso.


Objective The high demand for obesity treatment and conventional therapies' lack of effectiveness increases the use of alternative products. This study was aimed at assessing evidence from randomised clinical trials regarding the effectiveness of alternative weight-loss products' ingredients. Methods A survey was conducted in Ensenada, Baja California, to assess the frequency of consuming alternative products used for weight reduction. The ingredients in the products most in demand were included in this review. The Pubmed database was searched for all randomised clinical trial papers including these ingredients and assessing weight loss. Results Thirty-six percent of the subjects questioned had used alternative methods for weight-loss, 83 percent of them being women. The most frequently used products were shakes, tea, pills and flaxseed/linseed. Sixteen randomised clinical trials using four ingredients were used: Garcinia cambogia, green tea, L-carnitina and flaxseed. Only two studies (green tea and Garcinia cambogia) showed significant weight-loss (25 percent) amongst control and experimental groups. There was no significant difference between the groups in the studies regarding L-carnitina and flaxseed. Conclusions There is a lack of evidence regarding quality studies justifying the use of alternative products for weight loss.


Assuntos
Feminino , Humanos , Análise de Alimentos , Obesidade/terapia , Redução de Peso , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Rev Salud Publica (Bogota) ; 10(5): 818-30, 2008.
Artigo em Espanhol | MEDLINE | ID: mdl-19360230

RESUMO

OBJECTIVE: The high demand for obesity treatment and conventional therapies' lack of effectiveness increases the use of alternative products. This study was aimed at assessing evidence from randomised clinical trials regarding the effectiveness of alternative weight-loss products' ingredients. METHODS: A survey was conducted in Ensenada, Baja California, to assess the frequency of consuming alternative products used for weight reduction. The ingredients in the products most in demand were included in this review. The Pubmed database was searched for all randomised clinical trial papers including these ingredients and assessing weight loss. RESULTS: Thirty-six percent of the subjects questioned had used alternative methods for weight-loss, 83% of them being women. The most frequently used products were shakes, tea, pills and flaxseed/linseed. Sixteen randomised clinical trials using four ingredients were used: Garcinia cambogia, green tea, L-carnitina and flaxseed. Only two studies (green tea and Garcinia cambogia) showed significant weight-loss (25%) amongst control and experimental groups. There was no significant difference between the groups in the studies regarding L-carnitina and flaxseed. CONCLUSIONS: There is a lack of evidence regarding quality studies justifying the use of alternative products for weight loss.


Assuntos
Análise de Alimentos , Obesidade/terapia , Redução de Peso , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Gac. méd. Méx ; 142(6): 477-482, nov.-dic. 2006. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-568945

RESUMO

Objetivo. Informar las manifestaciones oftalmológicas en pacientes con granulomatosis de Wegener (GW). Método. Se revisó la base de datos del Instituto de Oftalmología Conde de Valenciana. Se recolectó la exploración oftalmológica completa, los exámenes de laboratorio y de gabinete, el tratamiento y la evolución. Resultados. Se incluyeron 11 pacientes con GW (18 ojos). Siete pacientes masculinos y 4 femeninos con edad promedio de 43.7 años (28-55). Tres habían tenido diagnóstico previo de GW y los 8 restantes se diagnosticaron en nuestro departamento. Siete presentaron cuadros bilaterales y 4 unilaterales. Las formas de presentación clínica fueron escleritis necrosante con queratitis ulcerativa periférica (QUP) (7/18), escleritis difusa (3/18), escleritis nodular (1/18), uveítis anterior no granulomatosa (1/18), neuropatía óptica isquémica (1/18), neuropatía óptica retrobulbar (1/18), desprendimiento de retina seroso (2/18) y dacriocistitis (2/18). De los 18 ojos, la capacidad visual final fue mejor o igual a 20/40 en 13, 20/400 en 3, cuenta dedos a 30cm o no-percepción de luz en 1. Actualmente 7 pacientes se encuentran en fase inactiva. Conclusiones. Las manifestaciones oftalmológicas más frecuentes en pacientes con GW fueron: escleritis necrosante y QUP. En la mayoría, la GW se diagnosticó después de las manifestaciones oftalmológicas, sin embargo, todos presentaron síntomas sistémicos u oftalmológicos previos.


OBJECTIVE: Report the ophthalmologic manifestations among patients with Wegener 's Granulomatosis (WG). METHOD: We reviewed the database of the Instituto de Oftalmologia Fundación Conde de Valenciana in order to collect information regarding complete ophthalmic examination, laboratory and cabinet tests, treatment, and disease progression. RESULTS: We included 11 patients with WG (18 eyes). Seven men and four women, mean age 43.7 years (range = 28-55). Three patients had a prior diagnosis of WG and the remaining eight patients were diagnosed by our study team. Seven subjects developed a bilateral affection and four had unilateral involvement. The clinical presentation was necrotizing scleritis with peripheral ulcerative keratitis (PUK) (7/18), diffuse scleritis (3/18), nodular scleritis (1/18), non-granulomatous uveitis (1/18), optic ischemic neuropathy (1/18), retrobulbar neuritis (1/18), serous retinal detachment (2/18), and dacryocystitis (2/18). Final visual acuity was better or equal to 20/40 (13/18), 20/400 (3/18), finger-counting or no-perception of light in 1/18. Currently, seven patients are symptom free. CONCLUSIONS: The most frequent ophthalmic manifestations among our patients with WG were: necrotizing scleritis and PUK. In most cases, WG was diagnosed after ophthalmic manifestations; however, all patients displayed prior systemic or ocular symptoms.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Granulomatose com Poliangiite/complicações , Inflamação/etiologia , Oftalmopatias/etiologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Imunossupressores/uso terapêutico , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Oftalmopatias/diagnóstico , Oftalmopatias/tratamento farmacológico , Resultado do Tratamento
20.
Gac Med Mex ; 142(6): 477-82, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17201110

RESUMO

OBJECTIVE: Report the ophthalmologic manifestations among patients with Wegener 's Granulomatosis (WG). METHOD: We reviewed the database of the Instituto de Oftalmologia Fundación Conde de Valenciana in order to collect information regarding complete ophthalmic examination, laboratory and cabinet tests, treatment, and disease progression. RESULTS: We included 11 patients with WG (18 eyes). Seven men and four women, mean age 43.7 years (range = 28-55). Three patients had a prior diagnosis of WG and the remaining eight patients were diagnosed by our study team. Seven subjects developed a bilateral affection and four had unilateral involvement. The clinical presentation was necrotizing scleritis with peripheral ulcerative keratitis (PUK) (7/18), diffuse scleritis (3/18), nodular scleritis (1/18), non-granulomatous uveitis (1/18), optic ischemic neuropathy (1/18), retrobulbar neuritis (1/18), serous retinal detachment (2/18), and dacryocystitis (2/18). Final visual acuity was better or equal to 20/40 (13/18), 20/400 (3/18), finger-counting or no-perception of light in 1/18. Currently, seven patients are symptom free. CONCLUSIONS: The most frequent ophthalmic manifestations among our patients with WG were: necrotizing scleritis and PUK. In most cases, WG was diagnosed after ophthalmic manifestations; however, all patients displayed prior systemic or ocular symptoms.


Assuntos
Oftalmopatias/etiologia , Granulomatose com Poliangiite/complicações , Inflamação/etiologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Oftalmopatias/diagnóstico , Oftalmopatias/tratamento farmacológico , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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