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Hypertension is associated with high circulating angiotensin II (Ang II). We have reported that autophagy regulates Ang II-induced vascular smooth muscle cell (VSMC) hypertrophy, but the mechanism mediating this effect is still unknown. Therefore, we studied how Ang II regulates LC3 levels in VSMCs and whether Bag3, a co-chaperone known to regulate LC3 total levels, may be involved in the effects elicited by Ang II. A7r5 cell line or rat aortic smooth muscle cell (RASMC) primary culture were stimulated with Ang II 100 nM for 24 h and LC3 I, LC3 II and Bag3 protein levels were determined by Western blot. MAP1LC3B mRNA levels were assessed by RT-qPCR. Ang II increased MAP1LC3B mRNA levels and protein levels of LC3 I, LC3 II and total LC3 (LC3 I + LC3 II). Cycloheximide, but not actinomycin D, abolished LC3 II and total LC3 increase elicited by Ang II in RASMCs. In A7r5 cells, cycloheximide prevented the Ang II-mediated increase of LC3 I and total LC3, but not LC3 II. Moreover, Ang II increased Bag3 levels, but this increase was not observed upon co-administration with either losartan 1 µM (AT1R antagonist) or Y-27632 10 µM (ROCK inhibitor). These results suggest that Ang II may regulate total LC3 content through transcriptional and translational mechanisms. Moreover, Bag3 is increased in response to Ang II by a AT1R/ROCK signalling pathway. These data provide preliminary evidence suggesting that Ang II may stimulate autophagy in VSMCs by increasing total LC3 content and LC3 processing.
Assuntos
Angiotensina II , Músculo Liso Vascular , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Cicloeximida/metabolismo , Cicloeximida/farmacologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , RNA Mensageiro/genética , RatosRESUMO
Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorption by osteoclasts. The secretion capacity of mature osteoblasts requires strict control of proteostasis. Endoplasmic reticulum-associated degradation (ERAD) prevents the accumulation of unfolded ER proteins via dislocation to the cytosol and degradation by the proteasome. The ER membrane protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which helps to stabilize the complex and facilitate the efficient degradation of unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded protein response and cellular stress. The aim of the current study was to establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast differentiation by measuring calcium deposit levels, alkaline phosphatase activity, and runt-related transcription factor 2 and osterix expression. We found that ERAD and proteasomal degradation were activated and that HERPUD1 expression was increased as osteoblast differentiation progressed. The absence of HERPUD1 blocked osteoblast mineralization in vitro and significantly reduced alkaline phosphatase activity. In contrast, HERPUD1 overexpression activated the osteoblast differentiation program. Our results demonstrate that HERPUD1 and ERAD are important for the activation of the osteoblast maturation program and may be useful new targets for elucidating bone physiology.-Américo-Da-Silva, L., Diaz, J., Bustamante, M., Mancilla, G., Oyarzún, I., Verdejo, H. E., Quiroga, C. A new role for HERPUD1 and ERAD activation in osteoblast differentiation and mineralization.
Assuntos
Diferenciação Celular/fisiologia , Degradação Associada com o Retículo Endoplasmático/fisiologia , Proteínas de Membrana/metabolismo , Osteoblastos/citologia , Osteogênese/fisiologia , Animais , Linhagem Celular , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Camundongos , Osteocalcina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics.
Assuntos
Cardiomiopatias Diabéticas/metabolismo , Insulina/metabolismo , Dinâmica Mitocondrial , Transdução de Sinais , Animais , Cardiomiopatias Diabéticas/patologia , Humanos , Modelos Biológicos , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
Insulin-like growth factor-1, angiotensin-(1-7) and angiotensin-(1-9) have been proposed to be important mediators in cardioprotection. A large body of evidence indicates that insulin like growth factor-1 has pleotropic actions in the heart (i.e., contractility, metabolism, hypertrophy, autophagy, senescence and cell death) and, conversely, its deficiency is associated with impaired cardiac function. Recently, we reported that insulin like growth factor-1 receptor is also located in plasma membrane invaginations with perinuclear localization, highlighting the role of nuclear Ca(2+) signaling in the heart. In parallel, angiotensin-(1-7) and angiotensin (1-9) acting through Mas receptor and angiotensin type 2 receptor have emerged as a novel anti-hypertensive molecules promoting vasodilatation and preventing heart hypertrophy. In this review we discuss the scientific evidence available regarding insulin-like growth factor-1, angiotensin-(1-7) and angiotensin-(1-9) in cardioprotection and its potential application as novel therapeutic targets for treating cardiac diseases.
Assuntos
Angiotensina I/fisiologia , Fármacos Cardiovasculares/farmacologia , Fator de Crescimento Insulin-Like I/fisiologia , Fragmentos de Peptídeos/fisiologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/efeitos dos fármacos , Humanos , Modelos Cardiovasculares , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/fisiologia , Receptor Tipo 2 de Angiotensina/fisiologia , Receptor IGF Tipo 1/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Sistema Renina-Angiotensina/fisiologia , Transdução de SinaisRESUMO
Interleukin-6 (IL-6) is an important myokine that is highly expressed in skeletal muscle cells upon exercise. We assessed IL-6 expression in response to electrical stimulation (ES) or extracellular ATP as a known mediator of the excitation-transcription mechanism in skeletal muscle. We examined whether the canonical signaling cascade downstream of IL-6 (IL-6/JAK2/STAT3) also responds to muscle cell excitation, concluding that IL-6 influences its own expression through a positive loop. Either ES or exogenous ATP (100 µM) increased both IL-6 expression and p-STAT3 levels in rat myotubes, a process inhibited by 100 µM suramin and 2 U/ml apyrase. ATP also evoked IL-6 expression in both isolated skeletal fibers and extracts derived from whole FDB muscles. ATP increased IL-6 release up to 10-fold. STAT3 activation evoked by ATP was abolished by the JAK2 inhibitor HBC. Blockade of secreted IL-6 with a neutralizing antibody or preincubation with the STAT3 inhibitor VIII reduced STAT3 activation evoked by extracellular ATP by 70%. Inhibitor VIII also reduced by 70% IL-6 expression evoked by ATP, suggesting a positive IL-6 loop. In addition, ATP increased up to 60% the protein levels of SOCS3, a negative regulator of the IL-6 signaling pathway. On the other hand, intracellular calcium chelation or blockade of IP3-dependent calcium signals abolished STAT3 phosphorylation evoked by either extracellular ATP or ES. These results suggest that expression of IL-6 in stimulated skeletal muscle cells is mediated by extracellular ATP and nucleotide receptors, involving IP3-dependent calcium signals as an early step that triggers a positive IL-6 autocrine loop.
Assuntos
Trifosfato de Adenosina/metabolismo , Sinalização do Cálcio/fisiologia , Interleucina-6/metabolismo , Músculo Esquelético/fisiologia , Animais , Animais Recém-Nascidos , Comunicação Autócrina/fisiologia , Cálcio/metabolismo , Células Cultivadas , Estimulação Elétrica , Espaço Extracelular/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
miRNAs, one of the members of the noncoding RNA family, are regulators of gene expression in inflammatory and autoimmune diseases. Changes in miRNA pool expression have been associated with differentiation of CD4+ T cells toward an inflammatory phenotype and with loss of self-tolerance in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) disease is a chronic multisystemic pathology, affecting the uvea, inner ear, central nervous system, and skin. Several lines of evidence support an autoimmune etiology for VKH, with loss of tolerance against retinal pigmented epithelium-related self-antigens. This deleterious reaction is characterized by exacerbated inflammation, due to an aberrant T H 1 and T H 17 polarization and secretion of their proinflammatory hallmark cytokines interleukin 6 (IL-6), IL-17, interferon γ, and tumor necrosis factor α, and an impaired CD4+ CD25 high FoxP3+ regulatory T cell function. To restrain inflammation, VKH is pharmacologically treated with corticosteroids and immunosuppressive drugs as first and second line of therapy, respectively. Changes in the expression of miRNAs related to immunoregulatory pathways have been associated with VKH development, whereas some genetic variants of miRNAs have been found to be risk modifiers of VKH. Furthermore, the drugs commonly used in VKH treatment have great influence on miRNA expression, including those miRNAs associated to VKH disease. This relationship between response to therapy and miRNA regulation suggests that these small noncoding molecules might be therapeutic targets for the development of more effective and specific pharmacological therapy for VKH. In this review, we discuss the latest evidence regarding regulation and alteration of miRNA associated with VKH disease and its treatment.
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ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca(2+) concentration, with an EC(50) value of 7.8 +/- 3.1 microm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 mum suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y(2) receptor and pannexin-1. As reported previously for electrical stimulation, 500 mum ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca(2+) homeostasis and muscle physiology.
Assuntos
Trifosfato de Adenosina/metabolismo , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Expressão Gênica , Músculo Esquelético/fisiologia , Animais , Apirase/farmacologia , Canais de Cálcio Tipo L/metabolismo , Linhagem Celular , Conexinas/genética , Conexinas/metabolismo , Estimulação Elétrica , Interleucina-6/genética , Interleucina-6/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Cloreto de Potássio/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Suramina/farmacologiaRESUMO
Introducción. Actualmente existe un aumento considerable de lesiones de miembros superiores en trabajadores con labores de escritorio y trabajo de escritorio. Una de las lesiones más comunes es el DHRMR (Dolor de Hombro Relacionado al Manguito Rotador).1,2 Por esta razón, la presente investigación buscó intervenir un grupo de trabajadores de oficina de la Universidad de Las Américas, campus Santiago Centro con dolor de hombro3, realizando pausas activas (PA), y ejercicios focalizados que buscaban aliviar el dolor y aumentar la funcionalidad. Objetivo. Comparar las PA basadas en ejercicios de fuerza, versus, las PA basadas en ejercicios de flexibilidad sobre las variables de función de hombro, dolor, dinamometría y síntomas asociados a sospecha de ansiedad y depresión en trabajadores administrativo de la Universidad de Las Américas, campus Santiago Centro. Métodos. Estudio pseudo-experimental, simple ciego (individuos no conocen a que grupo pertenecen), 40 participante mayores de 18 años que presentaron dolor de hombro en un periodo de 6 meses. Para la evaluación se utilizaron escalas DASH, ASES, EVA y GOLDBERG. Se separaron en dos grupos, grupo de ejercicios de fuerza y un grupo de ejercicios de flexibilidad, la aleatorización de los participantes en cada grupo se realizó con el software OxMaR. Resultados. Se observaron en todas las variables que no existieron diferencias significativas entre ambos grupos. Conclusión. No se observaron mayores diferencias entre ambas intervenciones, con una tendencia a una mayor mejoría al grupo de fuerza.
Background. Currently there is a considerable increase in upper limb injuries in workers with desk and teleworking tasks. One of the most common injuries is the DHRMR (Shoulder Pain Related to the Rotator Cuff).1,2 For this reason, the present investigation sought to intervene a group of office workers with shoulder pain3, performing active pauses (PA), and focused exercises that sought to relieve pain and increase functionality. Objective. To compare BP based on strength exercises versus BP based on flexibility exercises on the variables of shoulder function, pain, dynamometry, and symptoms associated with suspicion of anxiety and depression. Methods. Single-blind clinical trial, 40 subjects over 18 years of age who presented shoulder pain in a period of 6 months. For the evaluation, DASH, ASES, EVA and GOLDBERG scales were used. They were separated into two groups, a strength exercise group and a flexibility exercise group. Results. It was observed in all the variables that there were no significant differences between both groups. Conclusion. No major differences were observed between the two interventions, with a tendency to a greater improvement in the strength group.
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Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such as myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such as cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy. Moreover, cardiomyocytes are unable to regenerate; thus, lost cells are replaced with fibrotic tissue, with a potentially severe impact on myocardial function. Several therapeutic agents and strategies to reduce cardiomyocyte damage are currently available. This manuscript reviews the state of the art regarding novel cardioprotective endogenous peptides, such as neuregulin-1, angiotensin-(1-9), growth/differentiation factor-11, growth/differentiation factor- 15 and insulin-like growth factor-1. We discuss their protective effects and therapeutic potential in cardiovascular diseases and the current challenges to harnessing their full cardioprotective power. We also explore targeting of exosomes as a cardioprotective approach along with the therapeutic potential of cardiac regeneration strategies. Further advances associated with these molecules and cardioprotective approaches may provide more effective therapies to attenuate or prevent cardiomyocyte death, thereby preserving the myocardium.
Assuntos
Cardiotônicos/administração & dosagem , Sistemas de Liberação de Medicamentos/tendências , Cardiopatias/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Miócitos Cardíacos/fisiologia , Regeneração/fisiologiaRESUMO
A sample of 64 high-risk breast and/or ovarian cancer families from Chile were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIN no. 113705) and BRCA2 (MIN no. 600185) genes using conformation-sensitive gel electrophoresis, and the mutations found were confirmed with direct sequencing. Seven families (10.9%) were found to carry BRCA1 mutations and three families (4.7%) had BRCA2 mutations. Six different pathogenic mutations were detected in BRCA1, four that had been reported previously (c.187_188delAG; c.300T-->G, c.3450_3453delCAAG and IVS17-1G-->A) and two novel mutations (c.2605_2606delTT and c.4185_4188delCAAG). In BRCA2, we found three different pathogenic mutations, two previously described (c.6174delT and c.6503_6504delTT) and one novel mutation (c.5667delT). We also identified nine variants of unknown significance (five in BRCA1 and four in BRCA2). These findings indicate that the Chilean population has a heterogeneous spectrum of prevalent BRCA mutations. Given the results obtained in our study, the screening of the entire BRCA1 and BRCA2 coding regions is necessary for the molecular genetic testing of Chilean high-risk breast/ovarian cancer patients. To our knowledge, this is the first genetic study of BRCA gene mutations conducted in Chile. The Chilean population has a well-known admixed Amerindian-Caucasian ratio and, therefore, our findings are not only important per se, but they constitute the basis for improved and more specific genetic counselling, as well as to support for preventive campaigns geared toward the Chilean population.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , DNA de Neoplasias/genética , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Chile/epidemiologia , Feminino , Testes Genéticos , Genética Populacional , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologiaRESUMO
INTRODUCTION: Myocardial infarction (MI) is the leading cause of death. When MI is not lethal, heart failure (HF) is a major consequence with high prevalence and poor prognosis. The targeting of autophagy represents a potentially therapeutic approach for the treatment of both pathologies. AREAS COVERED: PubMed searches were performed to discuss the current state of the art regarding the role of autophagy in MI and HF. We review available and potential approaches to modulate autophagy from a pharmacological and genetic perspective. We also discuss the targeting of autophagy in myocardial regeneration. Expert commentary: The targeting of autophagy has potential for the treatment of MI and HF. Autophagy is a process that takes place in virtually all cells of the body and thus, in order to evaluate this therapeutic approach in clinical trials, strategies that specifically target this process in the myocardium is required to avoid unwanted effects in other organs.
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Autofagia , Insuficiência Cardíaca/terapia , Infarto do Miocárdio/terapia , Animais , Humanos , Miocárdio/patologiaRESUMO
Breast cancer is the most common malignancy among women. Chilean studies reveal that this cancer presents the third highest mortality rate. A family history of breast cancer is one of the major risk factors for the development of this disease. BRCA1 and BRCA2 are the two main hereditary breast cancer susceptibility genes, and mutations in these genes are related to inherited breast cancer. In specific populations only some mutations have been found to be associated with susceptibility. The purpose of this study was to establish the frequency of 5382insC (BRCA1) and 6174delT (BRCA2) germline mutations in 382 healthy Chilean women with at least two relatives affected with breast cancer and in probands and their relatives from 8 high risk families for breast cancer, using mismatch PCR assay. The results obtained showed that 5382insC and 6174delT mutations were not found in either of the groups studied. The ethnic origin of the contemporary Chilean population and the data reported in the literature suggest that these mutations may be absent or have a very low frequency in this population.. This genetic study is part of a breast cancer screening program that also includes annual mammography and clinical breast examination over a five-year period. Strategies to reduce morbidity and mortality associated with breast cancer lie in early detection in women with genetic risk.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile , Primers do DNA , Eletroforese em Gel de Ágar , Feminino , Humanos , Pessoa de Meia-Idade , Linhagem , Fenótipo , Reação em Cadeia da Polimerase/métodos , Fatores de RiscoRESUMO
BACKGROUND: Breast cancer is the most common malignancy among women, and is the second cause of cancer mortality among Chilean women. Female mortality due to breast cancer in Chile has shown a steady increase from 9.5 deaths per 100.000 women in 1985 to 12.8 deaths per 100.000 in 1995. A family history of breast cancer is one of the main risk factors for the development of the disease. BRCA1 and BRCA2 are two major hereditary breast cancer susceptibility genes. Mutations in these genes are associated to inherited breast cancer; 664 predisposing mutations have been described, but in specific populations only some of them, such as 185delAG have been found to be associated with susceptibility to breast cancer. AIM: To establish the frequency of the 185delAG mutation in the BRCA1 gene in Chilean healthy women with a family history of breast cancer. PATIENTS AND METHODS: The 185delAG mutation was studied by mismatch polymerase chain (PCR) reaction in 382 Chilean healthy women with at least two relatives affected with breast cancer. The PCR products were digested with the restriction enzyme HinfI. Digestion of the normal allele (170 pb fragment) produces a 150 pb fragment; the PCR product for the mutant allele does not contain a site for HinfI and therefore remains as a 170 bp fragment after digestion. RESULTS: One of the 382 healthy women presented the fragment of 170 pb after digestion with HinfI suggesting that she was heterozygous carrier for this mutation. The mutant patient had a mammography without suspicion of cancer. CONCLUSIONS: The frequency of the 185delAG mutation in BRCA1 was 0.26% (1/382) in Chilean healthy women with a family history of breast cancer.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile , Eletroforese em Gel de Ágar , Feminino , Deleção de Genes , Humanos , Hibridização In Situ , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Análise de Sequência de DNARESUMO
Breast cancer is the most common malignancy among women. Chilean studies reveal that this cancer presents the third highest mortality rate. A family history of breast cancer is one of the major risk factors for the development of this disease. BRCA1 and BRCA2 are the two main hereditary breast cancer susceptibility genes, and mutations in these genes are related to inherited breast cancer. In specific populations only some mutations have been found to be associated with susceptibility. The purpose of this study was to establish the frequency of 5382insC (BRCA1) and 6174delT (BRCA2) germline mutations in 382 healthy Chilean women with at least two relatives affected with breast cancer and in probands and their relatives from 8 high risk families for breast cancer, using mismatch PCR assay. The results obtained showed that 5382insC and 6174delT mutations were not found in either of the groups studied. The ethnic origin of the contemporary Chilean population and the data reported in the literature suggest that these mutations may be absent or have a very low frequency in this population.. This genetic study is part of a breast cancer screening program that also includes annual mammography and clinical breast examination over a five-year period. Strategies to reduce morbidity and mortality associated with breast cancer lie in early detection in women with genetic risk.
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama , Genes BRCA1 , Mutação , Idoso de 80 Anos ou mais , Chile , Primers do DNA , Eletroforese em Gel de Ágar , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17 % of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.
Assuntos
Humanos , Masculino , Feminino , Neoplasias da Mama/genética , Genes BRCA1 , Mutação/genética , Neoplasias Ovarianas/genética , Neoplasias da Mama Masculina/genética , Chile , Análise Mutacional de DNA , DNA de Neoplasias , População Branca , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Fatores de RiscoRESUMO
Revisan los últimos avances en diferentes áreas de la oftalmología, exponiendo la ventajas y las limitaciones de los métodos disgnósticos y terapéuticos en uso en la especialidad. El autor analiza los adelantos en la medición de la refracción ocular, lentes de contacto, estudio y tratamiento del glaucoma, cataratas y patología de retina, abordaje quirúrgico para corrección de las condiciones de refracción del ojo, microcirugía y aparición de nuevos instrumentos basados en el ultrasonido, radiología, láser y resonancia nuclear magnética, dando una amplia visión sobre el desarrollo de elevada tecnología experimentado últimamente en la oftalmología clínica
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Humanos , Oftalmologia/tendências , Glaucoma/reabilitação , Lentes de Contato/tendências , Lentes Intraoculares/tendências , Extração de Catarata/tendênciasRESUMO
El autor compara los resultados obtenidos prospectivamente con tres diseños de lentes intraoculares de cámara posterior, fabricados de una pieza de PMMA, con asas anguladas y de conformación en C, con cara posterior convexa, implantados en 115 ojos, divididos en tres series. En la primera serie, compuesta de 57 casos, se implantó un lente plano convexo. En la segunda y tercera series, compuestas por 44 y 19 casos, respectivamente, se implantó un lente biconvexo. El diseño de los modelos utilizados difiere notablemente de los modelos de tres piezas usualmente implantados. En la serie control, de 58 casos, se implantó lentes intraoculares de cámara posterior de tres piezas, con asas de polipropileno. En la primera serie se observó una mayor incidencia de pupilas ovales postop. así como una mayor frecuencia de precipitados pigmentarios sobre el lente en los primeros días de la observación postop. Dicho aspecto postoperatorio se presenta con mayor frecuencia que la observada con el uso de lentes de tres piezas según la experiencia del autor. No hay repercusión de estos hallazgos sobre el resultado visual en las series, comparado con la experiencia del autor con modelos de tres piezas. Se discuten los alcances de estos hallazgos y su proyección sobre los diseños de las asas y curvatura de las caras en lentes de una pieza de PMMA, analizando la literatura disponible. Asimismo se sugiere medidas para reducir el riesgo de implantación fuera del saco y de distorsión pupilar debido a las asas
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Humanos , Masculino , Feminino , Lentes Intraoculares/normasRESUMO
El uso de hialuronidasa como complemento de la mezcla anestésica para la administración de la anestesia peribulbar es evaluado prospectivamente en un estudio en 200 pacientes divididos al azar en un grupo con hialuronidasa + lidocaína + bupivacaína y otro grupo de lidocaína + bupivacaína. El agregado de hialuronidasa permite obtener mejor y más rápida anestesia ocular y de anexos, así como aquinesia de la musculatura extraocular y orbicular. Destaca la falta de proptosis y de hipertensión ocular. El uso de hialuronidasa no muestra efectos colaterales o indeseados en este estudio. Se revisa la bibliografía disponible sobre la materia y se comenta las ventajas generales de la anestesia peribular sobre la anestesia retroocular. Los autores consideran que el uso de hialuronidasa en anestesia peribulbar debe ser difundido y generalizarse a la práctica de la anestesia oftálmica