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Antecedentes y objetivo: La diabetes mellitus es la principal causa de enfermedad renal crónica (ERC) en nuestro país. El objetivo fue estimar la prevalencia global y por áreas sanitarias de ERC en la población diabética de Extremadura. Pacientes y métodos: Estudio observacional, longitudinal, retrospectivo en la población diabética atendida en el Sistema Extremeño de Salud durante el periodo 2012-2014. Se incluyeron 90.709 pacientes ≥ 18 años. El cálculo del filtrado glomerular estimado (FGe) se realizó mediante la ecuación CKD-EPI (derivada de la ecuación desarrollada por la Chronic Kidney Disease Epidemiology Collaboration) y se calculó el cociente albúmina/creatinina en orina (CAC). Se consideró paciente con ERC a todo aquel que en su última analítica tenía un FGe<60 mL/min/1,73 m2 y/o un CAC ≥ 30 mg/g, confirmados en una determinación previa separada al menos por tres meses. Resultados: La prevalencia global de ERC fue del 15,6% (17,5% en mujeres y 13,7% en varones) y fue mayor en la provincia de Cáceres (17%) que en la de Badajoz (14,8%, p<0,001), encontrándose la menor prevalencia en el área sanitaria de Navalmoral de la Mata (13%) y la mayor en la de Plasencia (17,8%, p < 0,001). La prevalencia de ERC definida sin necesidad de confirmación de la sostenibilidad del daño renal o del FGe disminuido fue del 26,1% (29,3% en mujeres y 22,9% en varones), lo que supone una sobreestimación de la prevalencia del 67%. Conclusiones: La prevalencia de ERC en población diabética extremeña es menor a la referida habitualmente y difiere significativamente entre sus áreas sanitarias. (AU)
Background and objective: Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in our country. The objective was to estimate the global prevalence and by health areas of CKD in the diabetic population of Extremadura. Patients and methods: Observational, longitudinal retrospective study in the diabetic population attended in the Extremadura Health System in 20122014. A total of 90,709 patients ≥ 18 years old were studied. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). The presence of CKD was defined as follows: an eGFR<60 mL/min/1.73 m2 in a time period of greater than three months or the presence of renal damage, as evaluated by an urine albumin-creatinine ratio (UACR) ≥ 30 mg/g, with or without reduced eGFR, also in a time period of greater than three months. Results: The overall prevalence of CKD was 15.6% (17.5% in women and 13.7% in men) and it was higher in the province of Cáceres (17%) than in Badajoz (14.8%, p<0.001), with the lowest prevalence in the Navalmoral de la Mata health area (13%) and the highest in Plasencia (17.8%, p<0.001). The prevalence of CKD defined without the need for confirmation of the sustainability of kidney damage or decreased eGFR was 26.1% (29.3% in women and 22.9% in men), which represents an overestimation of the prevalence of 67%. Conclusions: The prevalence of CKD in Extremadura's diabetic population is lower than usually referred to and differs significantly between its health areas. (AU)
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Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Insuficiência Renal Crônica , Diabetes Mellitus , Estudos Retrospectivos , Estudos Longitudinais , Albuminúria , Atenção Primária à SaúdeRESUMO
Introducción: La enseñanza de la ginecología y obstetricia abarca teoría y práctica, que tradicionalmente se impartieron presencialmente, situación que ha cambiado en 2020 debido a la pandemia de COVID-19.Material y métodos.Desarrollamos una herramienta docente basada en tecnologías de la información y la comunicación. AEGO es un asistente para la enseñanza de la ginecoobstetricia: clases filmadas durante consultas reales, técnicas semiológicas y sesiones de colposcopia, juego serio de visitas de control de embarazo, incluyendo procedimientos diagnósticos ginecoobstétricos y una encuesta de satisfacción.Resultados.El análisis de la encuesta realizada a 169 estudiantes indica que los temas que suscitaron mayor interés fueron las maniobras semiológicas y la consulta ginecológica. La encuesta evaluó la percepción de los estudiantes sobre la herramienta AEGO, que se evaluó en semiología obstétrica, con un 88% de satisfacción; semiología ginecológica, con un 95%; semiología en general, con un 80%; y manejo del parto, con un 95%. Preguntados sobre la equivalencia entre la enseñanza por AEGO y la enseñanza tradicional del curso a distancia instaurado a raíz de la pandemia, solamente el 7% de los estudiantes juzgó AEGO como insuficiente. En el ejemplo de metrorragias, los estudiantes juzgaron AEGO como equivalente a lo tradicional (47%) o complementario (44%). En cuanto a la prevención del cáncer genitomamario, el 43% consideró AEGO equivalente a la enseñanza 'presencial a distancia por zoom' y el 47% lo definió como complementario.Conclusión.AEGO es una herramienta muy útil para la enseñanza de la ginecología y la obstetricia, y tiene, potencialmente, la capacidad de incrementar los temas que se van a enseñar. (AU)
Introduction: The teaching of gynecology and obstetrics encompasses theory and practice were traditionally taught in presence, a situation that has changed in 2020 due to the COVID-19 pandemic.Material and methods.We developed a teaching tool based on information and communication technologies. AEGO is an assistant for the teaching of gynecoobstetrics: filmed classes during real consultations, semiological techniques and colposcopy sessions, serious set of pregnancy control visits, including gyneco-obstetric diagnostic procedures and a satisfaction survey.Results.The analysis of the survey of 169 students indicates: the topics that aroused the greatest interest were semiological maneuvers and gynecological consultation. The survey evaluated the students' perception of the AEGO tool that was evaluated in obstetric semiology with 88% satisfaction, gynecological semiology with 95%, semiology in general 80% and delivery management 95%. Asked about the equivalence between teaching by AEGO and the traditional teaching of the distance course established as a result of the pandemic, only 7% of students judged AEGO as insufficient. In the example of metrorrhagias, students judged AEGO as equivalent to traditional (47%) or complementary (44%). Regarding the prevention of genito-breast cancer, 43% considered AEGO equivalent to 'face-to-face distance learning by zoom' and 47% defined it as complementary.Conclusion.AEGO is a very useful tool for the teaching of gynecology and obstetrics and potentially has the ability to increase the topics to be taught (AU)
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Humanos , Educação Médica , Informática Médica , Tecnologia da Informação , Pandemias , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Inquéritos e QuestionáriosRESUMO
(1) Background: One of the most challenging parts in lingual orthodontics is the control and correction of the tip of anterior teeth, due to the occlusal open vertical slot of the incisors in lingual systems. The presented experimental in-vitro study was performed to determine the maximal tipping moment of the anterior teeth between two types of lingual brackets, the Incognito™ Appliance System (Incognito, TOP-Service, Bad Essen, Germany) and Tip-Bar™ system (Incognito, TOP-Service, Bad Essen, Germany). Furthermore, twelve different ligation methods and two different ligature materials were investigated. (2) Methods: The measurement was performed by assessing the stiffness and ultimate strength of the ligature in a uniaxial material testing machine (Instron, Norwood, MA, USA) using a 0.025 × 0.018 inch stainless steel wire. (3) The results showed that the highest precision for control tipping of anterior teeth was determined for the 0.010 inch Stainless Steel Tie (Pelz and Partner). Furthermore, the Tip-Bar™ brackets increased the maximal moment by 33.8% for elastic and steel ligatures. (4) Conclusions: The lateral tooth movement is highly dependent on the type of ligature and applied material during orthodontic treatment with lingual appliances. The use of 0.010 inch steel ligatures and the Tip-Bar™ bracket design results in better alignment in the anterior teeth segment.
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BACKGROUND AND OBJECTIVE: Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in our country. The objective was to estimate the global prevalence and by health areas of CKD in the diabetic population of Extremadura. METHODS: Observational, longitudinal retrospective study in the diabetic population attended in the Extremadura Health System in 2012-2014. A total of 90,709 patients ≥18 years old were studied. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). The presence of CKD was was defined as follows: an eGFR <60ml/min/1.73m2 in a time period≥of three months or the presence of renal damage, as evaluated by an urine albumin-creatinine ratio (UACR) ≥30mg/g, with or without reduced eGFR, also in a time period ≥ of three months. RESULTS: The overall prevalence of CKD was 15.6% (17.5% in women and 13.7% in men) and it was higher in the province of Cáceres (17.0%) than in Badajoz (14.8%, p<0.001), with the lowest prevalence in the Navalmoral de la Mata health area (13.0%) and the highest in Plasencia (17.8%, p<0.001). The prevalence of CKD defined without the need for confirmation of the sustainability of kidney damage or decreased eGFR was 26.1% (29.3% in women and 22.9% in men), which represents an overestimation of the prevalence of 67%. CONCLUSIONS: The prevalence of CKD in Extremadura's diabetic population is lower than usually referred to and differs significantly between its health areas.
Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Masculino , Humanos , Feminino , Adolescente , Estudos Retrospectivos , Prevalência , Insuficiência Renal Crônica/epidemiologia , Diabetes Mellitus/epidemiologia , Testes de Função RenalRESUMO
Diabetes mellitus (DM) is one of the leading causes of chronic kidney disease (CKD). We analyzed the prevalence of CKD in the population with diabetes in Extremadura (Spain). retrospective observational study was carried in the diabetic population attended in the Extremadura Health System in 2012-2014. A total of 38,253 patients, ≥18 years old were included. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. CKD was defined as follow: an eGFR <60 mL/min/1.73 m2 in a time period ≥ of three months or the presence of renal damage, with or without reduced eGFR, if the urine albumin-creatinine ratio (UACR) was ≥30 mg/g, also in a time period ≥ of three months. The prevalence rate of CKD was 25.3% (27.6% in women; 23.0% in men) and increases with age (34.0% in ≥65 years-olds). 24.9% of patients with CKD were in the very-high risk category for cardiovascular events (6.3% of the diabetic population). If CKD were diagnosed without requiring sustained eGFR <60 mL/min/1.73 m2 and/or sustained UACR ≥30 mg/g (as it is frequently found in the literature) this would overestimate the prevalence of CKD by 23%.
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AIMS: To analyze the prevalence of diabetes and the frequency of haemoglobin A1C (HbA1C) monitoring in the population with diabetes in Extremadura (Spain). METHODS: Observational, longitudinal retrospective study in the population attended in the Extremadura Health System in 2012-2014. A total of 403,644 glycated haemoglobin determinations in 189,466 subjects (52.4% female) were studied. All patients with a prescription of antidiabetic drugs and those who, despite not having treatment, had any determination of HbA1C ≥6.5% were considered as people with diabetes. All patients without treatment but with HbA1C ≥5.7% and <6.5% were considered prediabetes patients. RESULTS: The prevalence rate of diabetes was 8.3% and the frequency of HbA1C monitoring was 0.9/patient/year in the diabetic population. 48.2% of the patients with monitoring of HbA1C had diabetes, 21.2% had prediabetes, and 30.6% did not meet the criteria for diabetes or prediabetes. 12.7% of people with diabetes did not have determinations of HbA1C and only 11.8% have had ≥6 determinations in the period analyzed. CONCLUSIONS: The frequency of HbA1C monitoring in the diabetic population is lower than that usually recommended. Moreover, there is an inadequate use of HbA1C determinations, since one out of every 3 patients does not meet the criteria for diabetes or prediabetes.
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Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Hemoglobinas Glicadas/metabolismo , Padrões de Prática Médica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Bases de Dados Factuais , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de TempoRESUMO
Annual trivalent influenza vaccines contain one of influenza B lineages; influenza B/Victoria-lineage or influenza B/Yamagata viruses. Theoretically, these vaccines should protect against viruses expected to circulate in the next influenza season. The National Influenza Centers, based on surveillance data from National Reference Laboratories, selects the strains composing each annual trivalent or tetravalent vaccine. Nevertheless, in some epidemics, vaccine strains do not match genetically with circulating strains. The aim of the present study is to compare the HA1-domain of 42 influenza B viruses circulating in Cuba during the 2012-2013 season with the vaccine strain B/Wisconsin/01/2010-like virus from the B/Yamagata lineage, included in the 2012-2013 Northern-Hemisphere Influenza vaccine. The efficacy of the influenza vaccine was also estimated. The analysis of the present study indicates that the B/Victoria and B/Yamagata lineages co-circulated in Cuba in the 2012-2013 season. In 2012-2013 season, according to the sequences analysis, trivalent vaccine did not match with the circulating strains. The present study also detected amino acid substitutions which could have altered the antigenic properties of HA gene. The results presented here suggest the need to consider a possible introduction of tetravalent influenza vaccine in Cuba, as has been recommended by the WHO to ensure higher levels of protection.
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Reações Cruzadas/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Sequência de Aminoácidos , Antígenos Virais/química , Antígenos Virais/imunologia , Reações Cruzadas/genética , Cuba/epidemiologia , História do Século XXI , Humanos , Vírus da Influenza B/classificação , Vírus da Influenza B/genética , Vacinas contra Influenza/genética , Influenza Humana/história , Influenza Humana/virologia , Filogenia , Estações do AnoRESUMO
Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time.
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Variação Genética , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Antígenos Virais/genética , Cuba , Análise Mutacional de DNA , Estudos de Associação Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Filogenia , Conformação ProteicaAssuntos
Deriva Genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Cuba , História do Século XXI , Humanos , Vírus da Influenza A Subtipo H3N2/classificação , Influenza Humana/históriaRESUMO
Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed. All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis. We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT.
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Aneuploidia , Carcinoma Endometrioide/classificação , Carcinoma Endometrioide/genética , Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/genética , Instabilidade de Microssatélites , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Análise de SobrevidaRESUMO
Bovine abortions due to Neospora caninum infection have been reported worldwide and its economic impact on the beef industry has been acknowledged as a problem. Uruguay has the largest export value of beef per acre in South America. However, no data on the prevalence of N. caninum infection have been available in this country. The objective of this study was to estimate the prevalence and distribution of N. caninum infection in beef cattle in Uruguay through a nationwide survey. A two stage sampling design was used with farms being selected in stage one and animals being selected in stage two. A brief questionnaire was administered on each farm. Seroprevalence of N. caninum in 4444 beef cattle from 229 farms in all the counties, except Montevideo, of Uruguay was determined by an ELISA. The data were then analyzed to identify associations between infection and variables such as type of animal (cow or heifer), herd size, use of veterinary advice, productivity of the soil in relation to the national average, use of improved grass, use of mineral salts, use of supplemental feed, and presence of a dog(s) on the farm. The estimated proportion of positive farms for all the beef cattle operations was 69.2% (95% confidence interval [CI], 53.7-84.7). The overall cattle seroprevalence was estimated as 13.9% (95% CI, 11.6-16.3). The prevalence estimation by animal category was 14.3% (95% CI, 11.4-17.2) for beef cows and 12.9% (95% CI, 10.0-15.8) for beef heifers. There was no significant difference in the estimated prevalence between the two animal types. There was no significant difference in the animal level prevalence of N. caninum infection among different herd sizes. None of the herd demographic or management variables was significantly associated with the seropositivity to N. caninum infection. In conclusion, these results show that N. caninum infection is common among beef herds across Uruguay. Since the beef industry is one of the key industries in Uruguay, the economic effect and risk factors of N. caninum infection among beef cattle in this country should be further evaluated in the near future.
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Anticorpos Antiprotozoários/sangue , Doenças dos Bovinos/epidemiologia , Coccidiose/veterinária , Neospora/imunologia , Aborto Animal/parasitologia , Criação de Animais Domésticos/métodos , Animais , Bovinos , Coccidiose/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Masculino , Estudos Soroepidemiológicos , Uruguai/epidemiologiaRESUMO
This study describes the isolation of equine herpesvirus-2 (EHV-2) from the lung of an aborted equine fetus in Argentina. The isolated virus was confirmed as EHV-2 by indirect immunofluorescence using a rabbit anti-EHV-2 polyclonal antiserum and by virus-neutralization test using an equine polyclonal antibody against EHV-2. Restriction endonuclease DNA fingerprinting with BamHI also confirmed the identity of the virus as EHV-2. Furthermore, viral nucleic acid was detected by polymerase chain reaction from the original lung sample and from the DNA obtained from cells infected with the virus isolate. This work constitutes the first reported isolation of EHV-2 from an aborted equine fetus. The presence of EHV-2 in the lung of the aborted fetus would indicate that this virus is capable of crossing the placental barrier. However, no cause-effect relationship was established between the EHV-2 isolate and the abortion.
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Feto Abortado/virologia , Infecções por Herpesviridae/veterinária , Doenças dos Cavalos/virologia , Pulmão/virologia , Rhadinovirus/isolamento & purificação , Infecções Tumorais por Vírus/veterinária , Animais , Impressões Digitais de DNA/veterinária , DNA Viral/química , DNA Viral/genética , Desoxirribonuclease BamHI/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Infecções por Herpesviridae/virologia , Cavalos , Pulmão/embriologia , Testes de Neutralização/veterinária , Reação em Cadeia da Polimerase/veterinária , Gravidez , Rhadinovirus/genética , Infecções Tumorais por Vírus/virologiaRESUMO
For longer than 40 years, ultrasound (US) has been a widely used imaging tool in medical practice, which has proved helpful for the diagnosis and staging of diseases. Although three-dimensional ultrasound (3D) US has been available for more than 10 years, it was only through the development of the most recent computer technologies and its adaptation to ultrasound systems, that 3D US has become able to achieve the high level of sensitivity and performance necessary to be considered seriously in clinical practice. 3D US is rapidly turning into a technology with an ever-increasing range of applications in numerous fields because, among other reasons, it helps overcome some of the key limitations related to two-dimensional imaging. 3D US can be used in ultrasonography for small parts, among other medical areas. The assessment of the testicle, parotid, thyroid and parathyroid glands is properly achieved. The multiplanar presentation and niche mode are quite useful to determine the extension--inside or outside the organs-, of nodules, cysts or tumors. The volume measurement is better assessed with 3D US and given this, we can perform studies that follow growth in order to decide medical or surgical treatment. The VOCAL makes it possible to obtain a proper after-treatment follow-up of focal disorders in these small organs. Neovascularization is clearly viewed with 3D US and probably can suggest malignant origin of a neoplasm. 3D US offers a more comprehensive image of anatomical structures and pathological conditions and also permits to observe the exact spatial relationships. We are aware more studies are needed to demonstrate specificity and sensibility of 3D US in particular clinical conditions, not only in small parts but also is some other non-Ob/Gyn applications.
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Processamento de Imagem Assistida por Computador , Imageamento Tridimensional/métodos , Ultrassonografia Doppler em Cores/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Humanos , Imageamento Tridimensional/instrumentação , Masculino , Pessoa de Meia-Idade , Doenças das Paratireoides/diagnóstico por imagem , Doenças Parotídeas/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Doenças Testiculares/diagnóstico por imagem , Doenças da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia Doppler em Cores/instrumentação , VenezuelaRESUMO
Steroid-binding proteins unrelated to the classical nuclear receptors have been proposed to play a role in non-genomic effects of steroid hormones. We have previously described that the low-affinity glucocorticoid binding protein (LAGS), present in the endoplasmic reticulum of the male rat liver, has pharmacological and biochemical properties different from those of nuclear receptors. The LAGS is under multihormonal regulation and binds glucocorticoids, progestins, and synthetic steroids but is unable to bind either estradiol, testosterone, or triamcinolone acetonide. In this study, we have solubilized the LAGS and investigated their pharmacological and hydrodynamic properties and their peptide composition. We found that LAGS is an integral protein bound to the endoplasmic reticulum. CHAPS provided its optimal solubilization without changes in its pharmacological properties. Hydrodynamic properties of LAGS showed that it has a molecular mass of at least 135 kDa. SDS-PAGE of covalently-labeled LAGS showed that [3H]dexamethasone binds two peptides of 53 and 37 kDa, respectively. Thus, the LAGS appears as an oligomeric protein under multihormonal regulation. The availability of solubilized LAGS and the fact that it can be induced in vivo represent major steps toward purification and understanding the functional significance of this unique steroid-binding protein.
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Retículo Endoplasmático/metabolismo , Luz , Fígado/metabolismo , Animais , Membrana Celular/metabolismo , Centrifugação com Gradiente de Concentração , Cromatografia em Gel , Detergentes/farmacologia , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Estradiol/metabolismo , Glucocorticoides/metabolismo , Microssomos Hepáticos/metabolismo , Octoxinol , Peptídeos/química , Polietilenoglicóis/farmacologia , Progestinas/metabolismo , Ligação Proteica , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Esteroides/metabolismo , Frações Subcelulares/metabolismo , Testosterona/metabolismo , Fatores de Tempo , Triancinolona Acetonida/metabolismo , ÁguaRESUMO
Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the western countries. Withdrawal of androgens or the peripheral blockage of androgen action remain the critical therapeutic options for the treatment of advanced prostate cancer. However, after initial regression, most of the prostate cancers become androgen-independent and progress further, with eventual fatal outcome. Understanding the mechanisms of transition to androgen independence and tumor progression in prostate cancer is critical to finding new ways to treat aged patients that are ineligible for conventional chemotherapy. A large number of different molecular mechanisms might be responsible for the transition to androgen-independence. Many of these involve the androgen receptor (AR) and its signalling pathways, but they might also include genetic changes that affect several genes, which results in the activation of oncogenes or the inactivation of tumor suppressor genes. Here, we discuss the most recent and relevant findings on androgen resistance in prostate cancer in order provide a comprehensive interpretation of the clinical behaviour of tumors at molecular levels.
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Androgênios/metabolismo , Neoplasias da Próstata/metabolismo , Dimerização , Éxons , Humanos , Masculino , Modelos Biológicos , Mutação , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Ligação Proteica , Estrutura Terciária de Proteína , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais , Transcrição GênicaRESUMO
Several metabolic processes in the liver are regulated by thyroid hormone (T3). Gene expression profiles of livers from normal and TRbeta-deficient mouse strains should allow the classification of rapid and sustained effects of T3, as well as identification of target genes that are dependent on TRbeta. The immediate and long-term T3 regulation of about 4000 genes in livers from hypo- and hyperthyroid wild-type and TRbeta-deficient mice was analyzed using cDNA microarrays. T3 was found to regulate more than 200 genes, and among these, more than 100 were previously not described. Sixty percent of all these genes show dependence on the TRbeta gene for T3 regulation, indicating that TRalpha1 may have previously unknown functions in the liver. Analysis of the gene expression patterns showed a clear functional distinction between rapid (2 h) actions of T3 and late effects, seen after 5 d of sustained T3 treatment. Many metabolic actions were rapidly executed, whereas effects on mitochondrial function, for example, were seen after the sustained T3 treatment. As compared with wild-type controls, TRbeta-/-mice exhibited elevated expression of some target genes and reduced levels of others, indicating that both direct and indirect gene regulation by TRs in liver is complex and involves both ligand-dependent and -independent actions by the major TR isoforms.
