RESUMO
Gastric cancer (GC) is the fourth most deadly cancer globally. The adducin 1 (ADD1) protein is involved in oncogenic signal transduction pathways in several types of cancer, and the rs4961 variant (c.1378 G>T, p.Gly460Trp) of the ADD1 gene is associated with salt-sensitive hypertension, renal cell cancer and breast cancer susceptibility; however, it has not been investigated in GC. The aim of the present study was to evaluate the association between the rs4961 variant and the development of GC and preneoplastic gastric lesions (PGLs) in a population from western Mexico. A total of 225 individuals who underwent an endoscopy were evaluated, of which 71 patients had histopathologically diagnosed GC and 53 patients had PGLs, with 101 patients used as controls. The rs4961 variant was genotyped by using PCR and DNA sequencing. The frequency of the mutated homozygous genotype (TT) of the rs4961 variant was <10% in the three evaluated groups, and the frequency of the minor allele (T) was <21% in the GC, PGL and control groups. Genotypic and allelic frequencies were similarly distributed in all of the studied groups (P>0.05). In summary, in the study population, the rs4961 variant was not associated with GC risk; however, its role in other populations and in other types of cancer is worthy of future research.
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Paciente de 57 años, fumador, antecedentes de salud que acudió a consulta por presentar tos seca de 3 meses de evolución. Se le diagnosticó unteratoma mediastinal, tumor poco frecuente en esa edad. En la radiografía de tórax se observó una masa mediastinal anterior que se confirmó con la tomografía computarizada y donde la localización y las características imaginológicas sugirieron el diagnóstico. Se realizó esternotomía media con exéresis del tumor, confirmando por anatomía patológica la presencia de un teratoma quístico maduro en el mediastino(AU)
A 57 year old male smoking patient, with healthy history presented to the clinic for having dry cough for 3 months of evolution. Mediastinal teratoma was diagnosed, a rare tumor at that age. An anterior mediastinal mass was observed on the chest X-ray, which was confirmed by computed tomography. The location and imaging characteristics suggested the diagnosis as well. A median sternotomy was performed with tumor excision, the pathological anatomy confirmed the presence of a mature cystic teratoma in the mediastinum(AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Teratoma/patologia , Esternotomia/métodos , Neoplasias do Mediastino/diagnóstico por imagemRESUMO
Introducción: la Neumonía por Citomegalovirus (CMV) es una entidad rara en los pacientes inmunocompetentes, pero cuando se asocia con otras enfermedades como la neumonía, puede ser altamente letal. Objetivo: presentar un caso infrecuente de infección primaria por Citomegalovirus complicado con neumonía. Presentación del caso: se presenta el caso de una paciente de 36 años de edad, que trabajaba directamente con pacientes trasplantados renales, y que acudió a consulta por presentar fiebre de 38 oC en un período de más de 10 días, precedida de escalofríos, dolor de garganta, tos seca al inicio y luego expectoración de color verde claro; examen físico negativo; todo lo anterior acompañado de astenia marcada durante todo el día y anorexia. La falta de respuesta adecuada al tratamiento con Levofloxacino y Azitromicina nos hizo sospechar la presencia de una Neumonía viral por un germen de etiología no habitual, por lo que se le indicaron exámenes de anticuerpos anti-virales, resultando positivo para Citomegalovirus. Conclusiones: existen procesos inflamatorios pulmonares agudos reversibles de causa infecciosa sin manifestaciones auscultatorias, es decir con disociación clínico-radiológica, que en su mayoría corresponden a procesos de índole viral, y que además no son exclusivos de pacientes inmunodeprimidos(AU)
Introduction: Cytomegalovirus pneumonia is a rare disease in immunocompetent patients, but when associated to other diseases such as pneumonia, it becomes deadly. Objective: to present an uncommon case of primary Cytomegalovirus infection complicated with pneumonia. Case presentation: this is the case of a 36years-old patient who directly worked with renal transplanted patients and went to the doctor´s because of 38o fever for more than 10 days, thrills, throat ache, dry cough at the beginning and clear green colored sputum, negative physical examination results, and marked asthenia during the day and anorexia. The inadequate response to Levofloxacine and Azitromycin treatment made us suspect of viral pneumonia caused by an infrequent germ. Anti-viral antibodies tests were indicated to reveal positive results for Cytomegalovirus. Conclusions: there are reversible acute pulmonary inflammatory processes of infective origin without any manifestation on physical exam, that is, a clinical-radiological dissociation; the majority of these processes are of viral origin but they do not occur only in immunodepressed patients(AU)
Assuntos
Humanos , Feminino , Adulto , Infecções por Citomegalovirus/complicações , Pneumonia/diagnóstico , Pneumonia Viral/etiologiaRESUMO
Introducción: la Neumonía por Citomegalovirus (CMV) es una entidad rara en los pacientes inmunocompetentes, pero cuando se asocia con otras enfermedades como la neumonía, puede ser altamente letal. Objetivo: presentar un caso infrecuente de infección primaria por Citomegalovirus complicado con neumonía. Presentación del caso: se presenta el caso de una paciente de 36 años de edad, que trabajaba directamente con pacientes trasplantados renales, y que acudió a consulta por presentar fiebre de 38 oC en un período de más de 10 días, precedida de escalofríos, dolor de garganta, tos seca al inicio y luego expectoración de color verde claro; examen físico negativo; todo lo anterior acompañado de astenia marcada durante todo el día y anorexia. La falta de respuesta adecuada al tratamiento con Levofloxacino y Azitromicina nos hizo sospechar la presencia de una Neumonía viral por un germen de etiología no habitual, por lo que se le indicaron exámenes de anticuerpos anti-virales, resultando positivo para Citomegalovirus. Conclusiones: existen procesos inflamatorios pulmonares agudos reversibles de causa infecciosa sin manifestaciones auscultatorias, es decir con disociación clínico-radiológica, que en su mayoría corresponden a procesos de índole viral, y que además no son exclusivos de pacientes inmunodeprimidos...
Introduction: Cytomegalovirus pneumonia is a rare disease in immunocompetent patients, but when associated to other diseases such as pneumonia, it becomes deadly. Objective: to present an uncommon case of primary Cytomegalovirus infection complicated with pneumonia. Case presentation: this is the case of a 36years-old patient who directly worked with renal transplanted patients and went to the doctor´s because of 38o fever for more than 10 days, thrills, throat ache, dry cough at the beginning and clear green colored sputum, negative physical examination results, and marked asthenia during the day and anorexia. The inadequate response to Levofloxacine and Azitromycin treatment made us suspect of viral pneumonia caused by an infrequent germ. Anti-viral antibodies tests were indicated to reveal positive results for Cytomegalovirus. Conclusions: there are reversible acute pulmonary inflammatory processes of infective origin without any manifestation on physical exam, that is, a clinical-radiological dissociation; the majority of these processes are of viral origin but they do not occur only in immunodepressed patients...
Assuntos
Humanos , Adulto , Feminino , Infecções por Citomegalovirus/complicações , Pneumonia/diagnóstico , Pneumonia ViralRESUMO
Introducción: a pesar de los conocimientos alcanzados con respecto a la tuberculosis, esta enfermedad sigue siendo hoy en día la causa de muerte de muchos pacientes. Objetivo: describir el comportamiento de la mortalidad por o con tuberculosis, en los fallecidos de 60 años o más. Métodos: se estudiaron los 51 fallecidos de tuberculosis en Ciudad de La Habana entre los años 2005 y 2008. La informaci¾n se obtuvo a partir de la revisión de la base de datos de tuberculosis del Departamento de Higiene y Epidemiología de la Dirección Provincial de Salud de Ciudad de La Habana. Resultados: la investigación demostró que el 41,2 porciento falleció entre los 70 a 79 años de edad; predominó el sexo masculino con un 74,5 porciento y la pérdida de peso se asoció en el 47,1 porciento. Se realizó el diagnóstico en la atención secundaria de salud en el 68,2 porciento y la tuberculosis pulmonar representó el 96,1 porciento de los casos diagnosticados en vida, con esta localización. Predominaron los bacilos ácido alcohol resistente positivos (77,8 porciento) y el 100 porciento fueron casos nuevos. Conclusiones: aunque la atención primaria está totalmente estructurada a lo largo y ancho de nuestro país, los resultados de este trabajo indican que es una prioridad, el fortalecimiento en la detección de la enfermedad a este nivel de salud(AU)
Introduction: despite the knowledge gained on tuberculosis, this condition is still the cause of death for many patients. Objective: to describe the mortality behavior of tuberculosis in dead patients older than 60. Methods: an investigation was conducted on 51 deceased patients who died of tuberculosis from 2005 to 2008 in Havana City. The information was obtained by reviewing the Hygiene and Epidemiology Department tuberculosis database at Havana Public Health Provincial Direction. Results: this research showed that 41.2 percent of the patients died at 70 to 79 years old; there was male predominance (74.5 percent). Weight loss was associated in 47.1 percent of the cases. 68.2 percent had the diagnosis in secondary care level and pulmonary tuberculosis accounted for 96.1 percent of cases diagnosed when alive. Positive acid-fast bacilli resistant (77.8 percent) was predominant and 100 percent were new cases. Conclusions: although primary health care is fully structured throughout our country, the results of this study suggest the need for a strengthening in detecting this disease at this level of health care as a priority(AU)
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/mortalidade , Atenção Primária à Saúde/métodos , Fatores de RiscoRESUMO
Introducción: a pesar de los conocimientos alcanzados con respecto a la tuberculosis, esta enfermedad sigue siendo hoy en día la causa de muerte de muchos pacientes. Objetivo: describir el comportamiento de la mortalidad por o con tuberculosis, en los fallecidos de 60 años o más. Métodos: se estudiaron los 51 fallecidos de tuberculosis en Ciudad de La Habana entre los años 2005 y 2008. La informaci¾n se obtuvo a partir de la revisión de la base de datos de tuberculosis del Departamento de Higiene y Epidemiología de la Dirección Provincial de Salud de Ciudad de La Habana. Resultados: la investigación demostró que el 41,2 porciento falleció entre los 70 a 79 años de edad; predominó el sexo masculino con un 74,5 porciento y la pérdida de peso se asoció en el 47,1 porciento. Se realizó el diagnóstico en la atención secundaria de salud en el 68,2 porciento y la tuberculosis pulmonar representó el 96,1 porciento de los casos diagnosticados en vida, con esta localización. Predominaron los bacilos ácido alcohol resistente positivos (77,8 porciento) y el 100 porciento fueron casos nuevos. Conclusiones: aunque la atención primaria está totalmente estructurada a lo largo y ancho de nuestro país, los resultados de este trabajo indican que es una prioridad, el fortalecimiento en la detección de la enfermedad a este nivel de salud
Introduction: despite the knowledge gained on tuberculosis, this condition is still the cause of death for many patients. Objective: to describe the mortality behavior of tuberculosis in dead patients older than 60. Methods: an investigation was conducted on 51 deceased patients who died of tuberculosis from 2005 to 2008 in Havana City. The information was obtained by reviewing the Hygiene and Epidemiology Department tuberculosis database at Havana Public Health Provincial Direction. Results: this research showed that 41.2 percent of the patients died at 70 to 79 years old; there was male predominance (74.5 percent). Weight loss was associated in 47.1 percent of the cases. 68.2 percent had the diagnosis in secondary care level and pulmonary tuberculosis accounted for 96.1 percent of cases diagnosed when alive. Positive acid-fast bacilli resistant (77.8 percent) was predominant and 100 percent were new cases. Conclusions: although primary health care is fully structured throughout our country, the results of this study suggest the need for a strengthening in detecting this disease at this level of health care as a priority
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Atenção Primária à Saúde/métodos , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/patologia , Fatores de RiscoRESUMO
Se realizó un estudio observacional, analítico, prospectivo, en el período 2006-2008, en el Hospital Neumológico Benéfico Jurídico, con el objetivo de comparar los valores predictivos espirométricos de los enfermos candidatos a resección pulmonar con los obtenidos después de la intervención quirúrgica. La muestra quedó formada por 28 pacientes, residentes en Ciudad de La Habana. Para comparar el valor predictivo del volumen espiratorio forzado en el primer segundo con el valor real, seis meses después de la resección pulmonar se calculó el cociente delta relativo que expresó en porcentaje el grado de coincidencia entre estas dos variables. Una vez recogida la información se sometió a un análisis exploratorio de datos, con pruebas de significación asociadas. Los resultados mostraron que la espirometría clínica tiene un espacio indiscutible en la evaluación de la función pulmonar preoperatoria de los candidatos a resección pulmonar. Los valores predictivos y reales después de la resección pulmonar del volumen espiratorio forzado en el primer segundo fueron semejantes. La lobectomía superior izquierda fue el tipo de intervención quirúrgica con mayor similitud entre estos valores, por el contrario la neumectomía izquierda resultó ser la técnica con mayores diferencias entre los mismos(AU)
We carried out an observacional, analytical, prospective study in the period 2006-2008, at Neumologico Hospital Benéfico Jurídico, with the objective to compare the spirometry predicted values of the patients candidates to pulmonary surgery with the obtained ones after the operation. The sample was formed by 28 patients, residents in Havana City. In order to compare the predictive value of the forced expiratory volume in the first second with the real value six months after the pulmonary surgery, we calculated the quotient relative delta that expressed in percentage the degree of coincidence between these two variables. The information was put under an exploratory analysis of data, with associate tests of meaning. The results showed that the spirometry has an unquestionable space in the evaluation of the preoperating pulmonary function of the candidates to pulmonary surgery. The predictive and real values after the pulmonary surgery of the forced expiratory volume in the first second were similar. The left upper lobectomy was the type of operation with greater similarity between these values, on the contrary the left neumectomy turned out to be the technique with greater differences between such(AU)
Assuntos
Humanos , Masculino , Feminino , Pulmonaria , Espirometria , Estudos ProspectivosRESUMO
Se realizó un estudio observacional, analítico, prospectivo, en el período 2006-2008, en el Hospital Neumológico Benéfico Jurídico, con el objetivo de comparar los valores predictivos espirométricos de los enfermos candidatos a resección pulmonar con los obtenidos después de la intervención quirúrgica. La muestra quedó formada por 28 pacientes, residentes en Ciudad de La Habana. Para comparar el valor predictivo del volumen espiratorio forzado en el primer segundo con el valor real, seis meses después de la resección pulmonar se calculó el cociente delta relativo que expresó en porcentaje el grado de coincidencia entre estas dos variables. Una vez recogida la información se sometió a un análisis exploratorio de datos, con pruebas de significación asociadas. Los resultados mostraron que la espirometría clínica tiene un espacio indiscutible en la evaluación de la función pulmonar preoperatoria de los candidatos a resección pulmonar. Los valores predictivos y reales después de la resección pulmonar del volumen espiratorio forzado en el primer segundo fueron semejantes. La lobectomía superior izquierda fue el tipo de intervención quirúrgica con mayor similitud entre estos valores, por el contrario la neumectomía izquierda resultó ser la técnica con mayores diferencias entre los mismos(AU)
We carried out an observacional, analytical, prospective study in the period 2006-2008, at Neumologico Hospital Benéfico Jurídico, with the objective to compare the spirometry predicted values of the patients candidates to pulmonary surgery with the obtained ones after the operation. The sample was formed by 28 patients, residents in Havana City. In order to compare the predictive value of the forced expiratory volume in the first second with the real value six months after the pulmonary surgery, we calculated the quotient relative delta that expressed in percentage the degree of coincidence between these two variables. The information was put under an exploratory analysis of data, with associate tests of meaning. The results showed that the spirometry has an unquestionable space in the evaluation of the preoperating pulmonary function of the candidates to pulmonary surgery. The predictive and real values after the pulmonary surgery of the forced expiratory volume in the first second were similar. The left upper lobectomy was the type of operation with greater similarity between these values, on the contrary the left neumectomy turned out to be the technique with greater differences between such(AU)
Assuntos
Humanos , Masculino , Feminino , Espirometria/métodos , Volume Expiratório Forçado/fisiologia , Medidas de Volume Pulmonar/métodos , Margens de Excisão , Estudos ProspectivosRESUMO
Se presenta el caso de un paciente blanco de 47 años con cuadros respiratorios a repetición que cedían con tratamiento sintomático o con el uso de antibióticos por vía oral desde la infancia. A los 39 años de edad, comenzó con agudizaciones más frecuentes que requirieron tratamientos con antibióticos e ingresos en varios hospitales de Ciudad de La Habana, y se le diagnosticó Bronquiectasias diseminadas bilaterales e infectadas con Pseudomonas Aeruginosas, secundarias a una posible Tuberculosis adquirida en la antigua URSS a los 21 años. La falta de lesiones hacia los vértices pulmonares en la radiografía de tórax y el hecho de no haber nunca tenido hijos despertó la sospecha clínica de Fibrosis Quística, la cual fue confirmada por los estudios realizados posteriormente. Nuestro propósito al presentar este caso es alertar que esta enfermedad ha dejado de ser una patología exclusiva de Pediatría y que debe sospecharse ante un cuadro florido de bronquiectasias(AU)
The case of a 47 years old white patient, that presented repeated respiratory symptoms that only improve using symptomatic treatment or oral antibiotics. In 2000 when, he was 39 years old their symptoms increased and he required antibiotic intensive treatment and incomes at several hospital in Havana. After that, he was diagnosed with multiple bronchiectasis spread bilateral and infected Pseudomona Auriginosa, that could brings about, TB acquired at URSS when he was 21 years old. In 2008 because of the absence of lesions toward pulmonary apex in the Rx and the fact he couldn't have children aroused the clinical suspicion of Cystic Fibrosis and it was later confirmed by the accomplished studies. Our purpose to present this case is to alert and prevent that this disease has stopped being Pediatric's exclusive pathology and it should be taking into account when there is a complete picture of a multiple spread bronchiectasis(AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Bronquiectasia/complicações , Fibrose Cística/diagnóstico , Diagnóstico Tardio/efeitos adversos , Suor/metabolismo , Infertilidade Masculina/congênitoRESUMO
The receptor activator of nuclear factor-kappaB ligand (RANKL) and interleukin-1beta are osteoclast activating factors which are abnormally expressed in bone marrow stromal cells and plasma cells of multiple myeloma patients. In this work we analyzed RANKL expression in human bone marrow mesenchymal stromal cells and the effect of the bisphosphonate ibandronate on RANKL expression after IL-1beta activation of ERK pathway. Mesenchymal stromal cells were obtained from bone marrow iliac aspirates from multiple myeloma patients at stages II/III and non-osteoporotics control donors; these cells were maintained under long-term culture conditions. Cells were cultured in the presence or the absence of 5 ng/ml IL-1beta and/or 5 microM ibandronate, during selected periods. mRNA for RANKL and protein levels were assayed by RT-PCR and Western blot, respectively. Human bone marrow stromal cell line HS-5 was used for assessing IL 1beta- and ibandronate-ERK phosphorylation responses. Multiple myeloma mesenchymal stromal cells differentiate from control cells by increased basal RANKL expression. IL-1beta up regulated RANKL expression showed dependent on activated MEK/ERK pathway. Finally, the bisphosphonate ibandronate, that hindered activation of the MEK/ERK pathway significantly inhibited both basal and IL-1beta dependent RANKL expression by cells. Results indicate that RANKL expression involves the MEK/ERK pathway in multiple myeloma mesenchymal stromal cells, and that early obstruction of this path, such as that achieved with ibandronate, significantly deters RANKL protein expression.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Difosfonatos/farmacologia , Mieloma Múltiplo/metabolismo , Ligante RANK/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Idoso , Conservadores da Densidade Óssea/farmacologia , Células da Medula Óssea/citologia , Células Cultivadas , Inibidores Enzimáticos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Ácido Ibandrônico , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ligante RANK/genética , Transdução de Sinais/fisiologia , Células Estromais/citologiaRESUMO
Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor kappaB ligand (s-RANKL), tumor necrosis factor alpha, and interleukin 6 (IL-6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above-mentioned cytokines and also the level of the soluble receptors for both IL-6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual-energy X-ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow.
Assuntos
Tecido Adiposo/imunologia , Biomarcadores/sangue , Medula Óssea/imunologia , Reabsorção Óssea/sangue , Citocinas , Osteoporose Pós-Menopausa/imunologia , Pós-Menopausa/imunologia , Absorciometria de Fóton , Adipócitos/química , Adipócitos/imunologia , Idoso , Medula Óssea/química , Citocinas/análise , Feminino , Humanos , Inflamação , Osteoblastos/citologia , Osteoblastos/imunologia , Osteoprotegerina/sangueRESUMO
Human mesenchymal stem cells (hMSCs) are multipotent cells present in bone marrow, which differentiate into osteoblasts and adipocytes, among other lineages. Oestrogens play a critical role in bone metabolism; its action may affect the adipocyte to osteoblast ratio in the bone marrow. In hMSCs, oestrogens are synthesized from C19 steroids by the enzyme aromatase cytochrome P450. In this study, we assessed whether aromatase enzymatic activity varied through early osteogenic (OS) and adipogenic (AD) differentiation. Also, we studied the effect of leptin and 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on aromatase cell activity. Finally, we analysed whether conditions that modify oestrogen generation by cells affected hMSCs differentiation. For these purposes, hMSCs derived from post-menopausal women (65-86 years old) were cultured under basal, OS or AD conditions, in the presence or the absence of leptin and 1,25(OH)2D3. Aromatase activity was measured by the tritiated water release assay and by direct measurement of steroids synthesized from 3H-labelled androstenedione or testosterone. Our results showed that different OS and AD patterns of aromatase activity developed during the first period of differentiation (up to 7 days). A massive and sharp surge of aromatase activity at 24 h characterized early OS differentiation, while increased but constant aromatase activity was increased through adipogenesis. Both leptin and vitamin D increased aromatase activity during osteogenesis, but not during adipogenesis; finally, we showed that favourable aromatase substrates concentration restrained MSCs adipogenesis but improved osteogenesis. Thus, it could be inferred that a high and early increase of local oestrogen concentration in hMSCs affects their commitment either restraining AD or facilitating OS differentiation, or both.
Assuntos
Aromatase/metabolismo , Leptina/farmacologia , Células-Tronco Mesenquimais/enzimologia , Vitamina D/análogos & derivados , Adipócitos/citologia , Adipócitos/enzimologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Inibidores da Aromatase/farmacologia , Western Blotting/métodos , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Ativação Enzimática , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/fisiologia , Feminino , Fulvestranto , Humanos , Células-Tronco Mesenquimais/citologia , Microscopia de Fluorescência , Osteoblastos/citologia , Osteoblastos/enzimologia , Vitamina D/farmacologiaRESUMO
BACKGROUND AND AIMS: Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. METHODS: During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained. RESULTS: 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase. CONCLUSIONS: Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.
Assuntos
Dano ao DNA , Inflamação/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Aumento de Peso/fisiologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Aldeídos/metabolismo , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
There are disparate observations on central and peripheral effects of leptin, but several studies consistently support its role as a link between fat and bone. Bone marrow stroma contains mesenchymal stem cells (MSCs), which differentiate into osteoblasts and adipocytes, among others. In this study we assessed the expression of leptin receptors protein in MSCs from control and osteoporotic postmenopausal donors and their change during osteogenic and adipogenic differentiation. Also, we assessed the effects of leptin on osteogenic and adipogenic differentiation of these cells. We demonstrated high affinity leptin binding (KD = 0.36 +/- 0.02 nM) in both types of cells. Binding was very low under basal, but increased significantly (2-3 times) through osteogenic and adipogenic differentiation. Osteoporotic MSCs showed lower leptin binding capacity than control cells at an early osteogenic and adipogenic differentiation time, which could restrict cell sensitivity to the protective action of leptin. In this regard, we observed that leptin significantly inhibited adipocyte differentiation in control but not in osteoporotic MSCs, while it exerted a low stimulatory effect on calcium deposition (10%-20%) in both types of MSCs cells. In summary, we report the presence of high affinity leptin receptors on control and osteoporotic MSCs, which were modified distinctly by osteogenic and adipogenic stimulation and a direct and distinct effect of leptin on both type of cells.
Assuntos
Mesoderma/metabolismo , Osteoporose/metabolismo , Receptores de Superfície Celular/metabolismo , Células-Tronco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diferenciação Celular , Feminino , Humanos , Mesoderma/citologia , Osteoporose/patologia , Receptores para LeptinaRESUMO
Osteoblasts, the cells responsible for bone formation, derive from mesenchymal stem cells (MSCs) in bone marrow. To acquire a new cell phenotype, uncommitted MSCs must undergo several proliferation and differentiation changes. Although, it is known that extracellular signal-regulated protein kinases (ERKs) mitogen-activated protein (MAP) kinase pathway signaling is involved in the proliferation and differentiation processes, the role of ERKs in osteogenic differentiation it is controversial, at present. In addition, the function that ERK could play in MSCs derived from osteoporotic patients it is not well documented. In this study, we analyze whether previously observed differences in the dynamic response of MSCs from normal and osteoporotic postmenopausal women can be explained by changes in the activation of this signal transduction pathway. Levels of ERK phosphorylation and their correlation with osteogenic differentiation were evaluated in cultures of MSCs derived from osteoporotic postmenopausal women and "healthy" controls. The results show that, under basal conditions, MSCs derived from osteoporotic donors show a level of ERK phosphorylation 2.5 times higher than MSCs derived from control donors. The addition of the osteogenic stimulus only slightly increases the p-ERK level in cells derived from osteoporotic donors, and is higher in cells derived from control women. Important differences in the ability of PD98059 to inhibit phosphorylation of ERK in both types of cells were also observed, as well as the effect that this inhibition produced on calcium deposition. We conclude that the MAP kinase pathway signaling is differentially activated in MSCs derived from osteoporotic postmenopausal women. The high p-ERK levels in MSC derived from osteoporotic donors could determine the unresponsiveness of these cells to the osteogenic differentiation stimulus.
Assuntos
Células-Tronco Mesenquimais/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoporose Pós-Menopausa/enzimologia , Transdução de Sinais , Idoso , Estudos de Casos e Controles , Diferenciação Celular , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Células-Tronco Mesenquimais/patologia , Osteoporose Pós-Menopausa/patologia , Fosforilação/efeitos dos fármacosRESUMO
Cultures of skin fibroblasts show variation of androgen binding with culture conditions; binding variations are usually avoided by using confluent cultures. In this work, we analysed the effect of cell density and mitogenic agents on the level of androgen receptor (AR) of cultured human skin fibroblasts. Results demonstrated that in cultures of human skin fibroblasts, cellular binding of dihydrotestosterone was higher in cells grown at low than at high cell density. The reduction in binding resulted from a decrease in the number of high affinity receptors and not from a change in receptor affinity. Immunocytochemistry for AR showed greater staining intensity in cells grown at low than at high cell density. Additionally, immunoblot analysis demonstrated more AR protein in low cell density cultures. On the other hand, it was observed that cells grown at low cell density showed diminished androgen binding capacity after 24 h of treatment with insulin-like growth factor (IGF-l), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), or granulocyte-colony stimulating factor (G-CSF); this effect of growth factors was not observed in cells grown at high cell density. In conclusion, we found that cell density of cultures and mitogenic agents can regulate AR binding activity in human fibroblasts. While we do not yet know how changes in cell density affect the amount of AR, we conclude that the mechanism could be mediated by activation of the tyrosine kinase pathway, as the effect was reproduced by mitogens.
Assuntos
Receptores Androgênicos/fisiologia , Pele/citologia , Ciclo Celular , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Receptores Androgênicos/metabolismo , Pele/metabolismoRESUMO
Objetivos. Ofrecer una alternativa de educación sobre la diabetes con la participación de pacientes, familiares y personal sanitario, adaptada a las condiciones locales y a las necesidades sentidas por estas personas. Métodos. Se describe la metodología utilizada en una intervención educativa comunitara sobre la diabetes de tipo 2, dirigida a el primer nivel de atención. El estudio se realizó en el área de salud de El Guarco, Costa Rica. En una primera eatapa se hizo un estudio cualitativo sobre los conocimientos y prácticas de los paciente y del personal sanitario en relación con la prevención y el tratamiento de la diabetes y sobre la disponibilidad de alimentos en la comunidad. A partir de estos resultados, se desarrolló la metodología educativa, para lo cual se diseñaron un manual y dos procesos de capacitación sobre la diabetes, uno dirigido al personal sanitario y otros a los pacientes. Además, se desarrollaron estrategias comunitarias para dar sostenibilidad al proceso educativo. Resualtados. Se verificó que los pacientes no asocian el origen de la enfermedad con los antecedentes familiares ni el sobrepeso, que confunden los sitomas de hiperglucemia e hipoglucemia y que no hay homegeneidad en los mensajes de nutrición que reciben. Sobre la base del manual sobre diabetes, se capacitó al personal sanitario, cuyos conocimientos sobre el tratamiento y la prevención de la diabetes y sobre la metodología educativa mejoraron (promedio de 85 por ciento). A su vez, el personal sanitario capacitó a los pacientes diabéticos de su comunidad (edad:57,0 mas o menos 8,9 años, 92 por ciento mujeres(, quienes mostraron después del curso una disminución de la glucemia, de 189 mas o menos 79 mg/dL a 157 mas o menos 48 mg/dL (P=0,03), y de la hemoglobina glucosilada, de 11,3 mas o menos 2,4 por ciento a 9,7 man o menos 2,3 por ciento (P=0,05). No hubo cambios significativos del peso ni del perfil lipídico, a excepción de los tricglicéridos, que disminuyeron (P=0,040. Conclusiones. El nivel primario de atención es ideal para ejecutar programas educativos sobre el tratamiento y la detección temprana de la diabetes dirigidos a los pacientes, sus familiares y el personal sanitario. Se logró incorporar el programa educativo a la planificación anual del área de salud
Objective. To offer an educational alternative on diabetes, with the participation of patients with type 2 diabetes, their family members, and health care providers, adapted to local conditions and to these persons' felt needs. Methods. Focused on the primary-care level, this program was carried out in the health area of El Guarco, which is in the province of Cartago, Costa Rica. The first stage of the project included a qualitative study of the knowledge and practices of both patients and health care providers, looking at diabetes prevention and control and the local availability of foods. Based on those results, an educational methodology was developed, educational manuals were written, and courses for health care providers, patients, and patients' families were implemented. Other strategies were developed to make the effort sustainable. Results. We found that patients did not associate family history or obesity with diabetes and that those persons were also confused about the symptoms of diabetes. Patients also received inconsistent nutrition messages from health care providers. Using the diabetes education manual as a base, the providers increased their knowledge of diabetes prevention, treatment, and education by an average of 85%. The diabetic patients who received educational training (mean age, 57.0 years, with a standard deviation of 8.9 years; 92% women) improved their glycemic control. Blood glucose levels decreased from 189 ± 79 mg/dL (average and standard deviation) to 157 ± 48 mg/dL (P < 0.05), and glycosylated hemoglobin (HbA1c) went from 11.3% ± 2.4 % to 9.7% ± 2.3% (P = 0.05). There were no significant changes in body weight or lipid profile, except for triglycerides, which declined (P < 0.05). Conclusions. This educational program was successfully incorporated into the regular activities of the El Guarco-area health centers. The primary-care level is ideal for carrying out educational programs for diabetes treatment and early detection that are directed at patients, their families, and health care providers