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Purpose: The objectives of this project were to assess the current situation and management of cancer-related neuropathic pain (CRNP) in Spain and to provide specific recommendations for the assessment, diagnosis and treatment of CRNP using a Delphi methodology. Methods: This was a qualitative study that followed a Delphi methodology using a questionnaire with 56 statements that were grouped into 5 areas related to CRNP: prevalence and impact, pathophysiology, assessment and diagnosis, specific syndromes, treatment, and multidisciplinary approach. Based on the responses, the scientific committee prepared an algorithm and a recommended pathway for the management of CRNP. Results: Seventy-nine physicians attended the meeting and completed the questionnaire. Consensus was reached for all statements relating to the prevalence and impact of CRNP. However, the perceptions of specialists from palliative care of the frequency and impact of CRNP differed from those of other specialists. A high degree of consensus was reached for all statements concerning the assessment and diagnosis of CRNP. Regarding specific syndromes, the only statement with a lack of consensus was that on the frequency of NP in patients undergoing radiotherapy. There were some disagreements regarding the multidisciplinary approach and referral criteria for the management of NP. Conclusion: Our results show a large degree of agreement on the assessment, diagnosis and treatment of cancer-related neuropathic pain among the specialists involved in its management. There were, however, some disagreements regarding the multidisciplinary approach and referral criteria for the management of neuropathic pain.
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Salmonellosis is the second most prevalent zoonosis in Europe and it has considerable economic and health implications for its monitoring and control as well as being among the most prevalent pathogens on livestock farms. The wild boar (Sus scrofa) has been identified as a competent host and spreader of Salmonella spp. There has been a significant increase in wild boar population in Europe in recent decades, and it is even present in urban areas. This study evaluates the spatial distribution of the seroprevalence of Salmonella spp. in wild boar from Murcia (Southeast Spain) and its relationship with host-related risk factors (sex, age, location and density). The presence of antibodies against S. Typhimurium and Choleraesuis in 269 serum of wild boars hunted in Murcia between 2015 and 2019 were analyzed using a commercial ELISA test (PrioCHECK porcine Salmonella kit). The seroprevalence were spatially distributed using Kernel function, and wild boar density using Gaussian kernel estimates (spatialEco version 1.1.1). The risk function was estimated as the ratio between the intensity of positive samples and the wild boar density The overall seroprevalence was 19.3% (IC95% 16.9-21.8), showing a significant spatial aggregation. The highest seroprevalence detected was 51.8% (IC95% 42.2-61.5) in a specific area with high risk of infection (76-100%) and was related to the wild boar density. Only marginal differences were detected for sex and age. The use of ELISA combined with QGIS (version 3.6.0) has allowed the identification of areas of Salmonella occurrence associated with high density as risk factor.
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Salmonelosis Animal/epidemiología , Enfermedades de los Porcinos/epidemiología , Animales , Animales Salvajes , Densidad de Población , Prevalencia , Salmonelosis Animal/microbiología , Estudios Seroepidemiológicos , España/epidemiología , Sus scrofa , Porcinos , Enfermedades de los Porcinos/microbiologíaRESUMEN
Clusterin is a multifunctional glycoprotein whose role in cells has generated a great controversy in recent years. Since its discovery, numerous studies have linked clusterin expression deregulation with various physio-pathological processes such as cancer or Alzheimer's disease. Although the results of such investigations have sometimes been contradictory, mainly due to the dichotomous role of clusterin isoforms, it has been demonstrated that this protein is involved in diverse cellular processes, including apoptosis, cell cycle regulation, DNA repair or the acquisition of cell resistance against multiple conventional therapies. These results, together with the breakthrough of gene therapies, have motivated a great effort to elucidate the importance of clusterin as a potential therapeutic target. However, the understanding of a single gene, with multiple RNA transcripts and several protein isoforms has turned out to be a complex task. In this review, we summarize the studies published to date on factors that can affect clusterin expression and evaluate if a better understanding of this complex gene/protein would be useful to develop new treatment strategies for cancer and other pathologies.
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Clusterina/metabolismo , Enfermedad de Alzheimer/metabolismo , Apoptosis , Clusterina/genética , Reparación del ADN , Regulación de la Expresión Génica , Terapia Genética , Humanos , Terapia Molecular Dirigida/métodos , Neoplasias/metabolismo , Neoplasias/terapia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transducción de SeñalRESUMEN
Actualmente existe evidencia suficiente que avala la importancia de las intervenciones en fases tempranas de la psicosis. El retraso en la detección y el tratamiento del primer episodio psicótico se asocia con una recuperación menor y más lenta, así como con un riesgo mayor de recaídas. A pesar de ello, todavía no se han implementado de forma regular programas de intervención temprana en los servicios de salud mental en España. En este artículo de opinión se revisarán los principales argumentos que nos permitan defender la necesidad de la implementación de estos programas y las estrategias a seguir para cumplir con este objetivo. Existen actualmente programas de intervención temprana para la psicosis bien establecidos en otros países que incluyen intervenciones farmacológicas y psicosociales, junto con actividades de sensibilización al público, de colaboración entre familias y profesionales y de difusión de información. Los datos publicados acerca de la experiencia de estos programas ya instaurados indican que esta atención es eficiente no solo en términos de salud, sino también desde el punto de vista económico. Se resumen en este artículo las principales acciones y estrategias para la implementación de servicios de atención temprana en nuestro país (AU)
There is now sufficient evidence to support the importance of interventions in the early stages of psychosis. The delay in the detection and treatment of the first-episode psychosis is related to a lower and slower recovery, as well as a higher risk of relapse. Despite this fact, early intervention units or teams are still not regularly implemented in mental health service settings in Spain. In this opinion article, a review is presented of the main arguments for defending the need to implement these programs and strategies in order to achieve this aim. There are a number of programs for early intervention for psychosis currently working in other countries, with a therapeutic program that includes pharmacological and psychosocial interventions, together with public awareness, information dissemination, and family-professional collaboration activities. Published literature on the experience of these programs indicates that early intervention is not only effective in terms of the improvement of health status, but is also economically efficient. The main steps and recommendations needed to implement such early intervention programs in our country are described (AU)
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Humanos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/prevención & control , Intervención Médica Temprana/métodos , Episodio de Atención , Esquizofrenia/epidemiología , Prevención Primaria/tendencias , España/epidemiología , Prevención Secundaria/tendencias , Prevención Terciaria/tendencias , Servicios de Salud MentalRESUMEN
There is now sufficient evidence to support the importance of interventions in the early stages of psychosis. The delay in the detection and treatment of the first-episode psychosis is related to a lower and slower recovery, as well as a higher risk of relapse. Despite this fact, early intervention units or teams are still not regularly implemented in mental health service settings in Spain. In this opinion article, a review is presented of the main arguments for defending the need to implement these programs and strategies in order to achieve this aim. There are a number of programs for early intervention for psychosis currently working in other countries, with a therapeutic program that includes pharmacological and psychosocial interventions, together with public awareness, information dissemination, and family-professional collaboration activities. Published literature on the experience of these programs indicates that early intervention is not only effective in terms of the improvement of health status, but is also economically efficient. The main steps and recommendations needed to implement such early intervention programs in our country are described.
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Intervención Médica Temprana/provisión & distribución , Accesibilidad a los Servicios de Salud , Trastornos Psicóticos/terapia , Esquizofrenia/terapia , Intervención Médica Temprana/métodos , Intervención Médica Temprana/organización & administración , Medicina Basada en la Evidencia , Humanos , Trastornos Psicóticos/diagnóstico , Recurrencia , Esquizofrenia/diagnóstico , España , Resultado del TratamientoRESUMEN
The efficacy of protein kinase inhibitors (PKIs) has been shown in clinical assays for cancer, but as isolated agents, they only have a modest effect. One of the most important characteristics of mitogen-activated PKIs is their ability to decrease the apoptotic threshold of cancer cells, sensitizing them to the action of other antiapoptotic agents. The secretory clusterin protein is an inhibitor of apoptosis with a cytoprotective function. We describe the use of clusterin-specific antisense oligonucleotides and siRNA to sensitize breast carcinoma cells to several PKIs. MCF-7 and MDA-MB-231 cells were treated with antisense oligonucleotide or siRNA to clusterin and the following PKIs: H-89, chelerythrine and genistein. The three inhibitors used in this study upregulated clusterin expression and treatments that included antisense oligonucleotide or siRNA to clusterin reduced the number of viable cells more effectively than did treatment with the drugs alone. Therefore, treatment with such combinations may benefit patients with breast cancer.
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Neoplasias de la Mama/metabolismo , Clusterina/metabolismo , Oligonucleótidos Antisentido/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Benzofenantridinas/farmacología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Clusterina/genética , Regulación hacia Abajo , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Femenino , Genisteína/farmacología , Humanos , Isoquinolinas/farmacología , ARN Interferente Pequeño/genética , Sulfonamidas/farmacología , Tionucleótidos/farmacologíaRESUMEN
Cancer immunosurveillance theory has emphasized the role of escape mechanisms in tumor growth. In this respect, a very important factor is the molecular characterization of the mechanisms by which tumor cells evade immune recognition and destruction. Among the many escape mechanisms identified, alterations in classical and non-classical HLA (Human Leucocyte Antigens) class I and class II expression by tumor cells are of particular interest. In addition to the importance of HLA molecules, tumor-associated antigens and accessory/co-stimulatory molecules are also involved in immune recognition. The loss of HLA class I antigen expression and of co-stimulatory molecules can occur at genetic, transcriptional and post-transcriptional levels. Epigenetic defects are involved in at least some mechanisms that preclude mounting a successful host-antitumor response involving the HLA system, tumor-associated antigens, and accessory/co-stimulatory molecules. This review summarizes our current understanding of the role of methylation in the regulation of molecules involved in the tumor immune response.
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A 17-year-old-female at 39 weeks gestation, presented with pelvic pain, proteinuria and a decrease in fetal heart rate. Timely caesarean section was performed. The postoperative course was complicated by acute renal failure, acute pancreatitis, acute liver failure, anemia, thrombocytopenia, systemic inflammatory response syndrome (SIRS), prolonged coagulopathy, hyperbilirubinemia, ecclampsia, and psychosis. The clinical features and laboratory abnormalities, in conjunction with the timing of gestational age, led to the diagnosis of acute fatty liver of pregnancy. Prompt diagnosis and supportive care in an intensive care unit provided for a positive outcome.
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Cesárea , Cuidados Críticos/métodos , Hígado Graso/diagnóstico , Complicaciones del Embarazo/diagnóstico , Trastornos Puerperales/etiología , Desprendimiento Prematuro de la Placenta/cirugía , Enfermedad Aguda , Adolescente , Transfusión de Componentes Sanguíneos , Terapia Combinada , Hígado Graso/cirugía , Femenino , Sufrimiento Fetal/etiología , Sufrimiento Fetal/cirugía , Fluidoterapia , Glucosa/uso terapéutico , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/etiología , Enfermedades Hematológicas/terapia , Humanos , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/etiología , Pancreatitis/etiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Embarazo , Complicaciones del Embarazo/cirugía , Proteinuria/etiología , Trastornos Psicóticos/etiología , Trastornos Puerperales/terapia , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/terapiaRESUMEN
BACKGROUND/AIMS: Clusterin has attracted much recent attention because of its association with tumorigenesis and the progression of human carcinomas. The present study was designed to examine the role of clusterin methylation as an indicator of clusterin expression in tumor cell lines and breast tissue samples. METHODS: For this purpose, we used methylation-sensitive restriction analysis followed by PCR. RESULTS: None of the non-tumoral breast samples showed expression of clusterin by immunohistochemistry, and a methylated state was found in the promoter region of the gene. However, a demethylated state was found in 5 of 6 analyzed carcinoma cell lines. Four of 5 demethylated cell lines presented moderate to strong expression of clusterin, while no expression was detected in the unmethylated cell line. The inverse correlation found in most cell lines between clusterin expression and promoter methylation was also found in most human tumors analyzed (p < 0.001). Thus, a methylated state was present in 14 carcinomas, 12 of them with a null expression of clusterin, while a demethylated state was detected in 7 breast tumor samples, with 5 of them presenting strong expression. CONCLUSIONS: We conclude that clusterin expression is under epigenetic control via methylation of its promoter.
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Clusterina/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Clusterina/metabolismo , Femenino , Humanos , Inmunohistoquímica , Células K562 , Leucocitos/metabolismo , Masculino , Neoplasias/metabolismo , Neoplasias/patología , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espermatozoides/metabolismoRESUMEN
El objetivo del presente estudio es evaluar el riesgo en salud sexual y reproductiva de las madres y usuarias de los hogares comunitarios FAMI del Instituto Colombiano de Bienestar Familiar del Municipio de Los Patios. Para evaluar el riesgo en salud sexual y reproductiva fué necesario determinar los conocimientos, actitudes y prácticas en los aspectos relacionados con la sexualidad, planificación familiar, infecciones de transmisión sexual, embarazo y parto. Se aplicó una encuesta a 715 mujeres de las cuales 68 son madres FAMI y el restante son usuarias adscritas a los programas ofrecidos por estos hogares, durante el período comprendido entre marzo a junio del 2007. La encuesta está distribuida en dos partes: una que incluye datos sociodemográficos y otra que evalúa los conocimientos, actitudes y prácticas en salud sexual y reproductiva. Los resultados de la evaluación del riesgo general muestra que el 41,97% de las madres y usuarias de los hogares comunitarios FAMI del municipio de Los Patios tienen riesgo sexual y reproductivo de acuerdo con el nivel de conocimientos, actitudes y prácticas de sexualidad, planificación familiar, infecciones de transmisión sexual, embarazo y parto siendo clasificado en un nivel medio de riesgo. En conclusión, la población encuestada por sus condiciones demográficas de conocimiento, actitud y práctica frente a procesos como la sexualidad, planificación familiar, infecciones de transmisión sexual, embarazo y parto se clasifica en un nivel medio de riesgo sexual y reproductivo; sin embargo, es necesario que el sector salud junto con organizaciones sociales encargadas para el cuidado de la mujer tomen medidas que conlleven a la identificación de este problema e intervengan de forma adecuada y oportuna para la disminución del riesgo en salud sexual y reproductiva.
The objective of the present study is to evaluate the risk in Sexual Health and Reproductive of the mothers and users of communitarian homes FAMI of the Colombian Institute of welfare Family of the Municipality of the Patios. In order to evaluate the risk in Sexual Health and Reproductive it was necessary to determine the knowledge, attitudes and practices in the aspects related to the sexuality, familiar planning, infections of sexual transmission, pregnancy and childbirth. Asurvey to 715 women was applied of who 68 are mothers FAMI and the rest usuary is assigned to the programs offered by these homes, during the period between March to June of the 2007. The survey is distributed in two parts one that includes sociodemographic data and other than evaluates the knowledge, attitudes and practices in SSR. The results of the evaluation of the general risk sample that 41.97% of the mothers and users of communitarian homes FAMI of the Municipality of the Patios have sexual and reproductive risk in agreement with the level of knowledge, attitudes and practices of sexuality, familiar planning, infections of sexual transmission and pregnancy and childbirth being classified in a mean level of risk. In conclusion the population survey by its demographic conditions of knowledge, attitude and practice in front of processes like the sexuality, familiar planning, infections of sexual transmission, pregnancy and childbirth classifies itself in a mean level of sexual risk and reproductive nevertheless it is necessary that the sector health along with in charge social organizations for the care and the woman take measures that entail to the identification of this problem and take part of suitable and opportune form for the diminution of the risk in Sexual Health and Reproductive.
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Salud Reproductiva , Conocimientos, Actitudes y Práctica en Salud , RiesgoRESUMEN
INTRODUCTION: Overexpression of the apoptosis-related protein clusterin is associated with breast cancer development and tumor progression. We describe the use of clusterin-specific antisense oligonucleotides and antibodies to sensitize breast carcinoma cells to anticancer drugs routinely used in breast cancer therapy. METHODS: MCF-7 and MDA-MB-231 cells were treated with the oligonucleotide or antibody, chemotherapeutic agents (doxorubicin or paclitaxel), tamoxifen, or with combinations of these. RESULTS: Treatments that include antisense clusterin oligonucleotide or antibody to clusterin have been shown to reduce the number of viable cells more effectively than treatment with the drugs alone. We also demonstrate that dexamethasone pretreatment of breast cancer cell lines inhibits chemotherapy-induced cytotoxicity and is associated with the transcriptional induction of clusterin. However, anticlusterin treatment increases chemotherapy-induced cytotoxicity, even in the presence of glucocorticoids, suggesting a possible role for these proteins in glucocorticoid-mediated survival. CONCLUSION: These data suggest that combined treatment with antibodies to clusterin or antisense clusterin oligodeoxynucleotides and paclitaxel, doxorubicin, or tamoxifen could be a novel and attractive strategy to inhibit the progression of breast carcinoma by regulation of the clusterin function. Moreover, glucocorticoid activation in breast cancer cells regulates survival signaling by the direct transactivation of genes like clusterin which encode proteins that decrease susceptibility to apoptosis. Given the widespread clinical administration of dexamethasone before chemotherapy, understanding glucocorticoid-induced survival mechanisms is essential for achieving optimal therapeutic responses.
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Antineoplásicos/efectos adversos , Antineoplásicos/antagonistas & inhibidores , Neoplasias de la Mama/tratamiento farmacológico , Clusterina/antagonistas & inhibidores , Clusterina/metabolismo , Dexametasona/antagonistas & inhibidores , Oligonucleótidos Antisentido/farmacología , Anticuerpos Antineoplásicos/farmacología , Antineoplásicos/farmacología , Antineoplásicos Hormonales/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Clusterina/genética , Clusterina/inmunología , Dexametasona/farmacología , Doxorrubicina/antagonistas & inhibidores , Doxorrubicina/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucocorticoides/antagonistas & inhibidores , Humanos , Etiquetado Corte-Fin in Situ , Paclitaxel/antagonistas & inhibidores , Paclitaxel/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tamoxifeno/farmacología , Transcripción Genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.