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The stability and reactivity of Pd4Ni4 and Pd4Cu4 clusters embedded on graphene modified by monovacancy and nitrogen doping were investigated using auxiliary density functional theory (ADFT) calculations. The most stable structure of the Pd4Ni4 cluster is found in high spin multiplicity, whereas the lowest stable energy structure of the Pd4Cu4 cluster is a close shell system. The interaction energies between the bimetallic clusters and the defective graphene systems are significantly higher than those reported in the literature for the Pd-based clusters deposited on pristine graphene. It is observed that the composites studied present a HOMO-LUMO gap less than 1 eV, which suggests that they may present a good chemical reactivity. Therefore, from the results obtained in this work it can be inferred that the single vacancy graphene and pyridinic N-doped graphene are potentially good support materials for Pd-based clusters.
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BACKGROUND: The outbreak of SARS-CoV-2 abruptly disseminated in early 2020, overcoming the capacity of health systems to respond the pandemic. It was not until the vaccines were launched worldwide that an increase in survival was observed. The objectives of this study were to analyse the characteristics of survivors and their relationship with comorbidities. We had access to a database containing information on 16,747 hospitalized patients from Mexico, all infected with SARS-CoV-2, as part of a regular follow-up. The descriptive analysis looked for clusters of either success or failure. We categorized the samples into no comorbidities, or one and up to five coexisting with the infection. We performed a logistic regression test to ascertain what factors were more influential in survival. The main variable of interest was survival associated with multimorbidity factors. The database hosted information on hospitalized patients from Mexico between March 2020 through to April 2021. Categories 2 and 3 had the largest number of patients. Survival rates were higher in categories 0 (64.8%), 1 (57.5%) and 2 (51.6%). In total, 1741 (10.5%) patients were allocated to an ICU unit. Mechanical ventilators were used on 1415 patients, corresponding to 8.76%. Survival was recorded in 9575 patients, accounting for 57.2% of the sample population. Patients without comorbidities, younger people and women were more likely to survive.
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Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.
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Anemia/diagnóstico , Anemia/terapia , Hematínicos/uso terapéutico , Hierro/administración & dosificación , Neoplasias/complicaciones , Algoritmos , Anemia/sangre , Anemia/complicaciones , Anemia Ferropénica/complicaciones , Anemia Ferropénica/diagnóstico , Diagnóstico Diferencial , Suplementos Dietéticos/efectos adversos , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Femenino , Hematínicos/efectos adversos , Humanos , Hierro/efectos adversos , Masculino , Oncología Médica , Neoplasias/mortalidad , Calidad de Vida , Sociedades Médicas , EspañaRESUMEN
Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.
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Inhibidores del Factor Xa/uso terapéutico , Neoplasias/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Humanos , Guías de Práctica Clínica como Asunto , Tromboembolia Venosa/etiologíaRESUMEN
La coinfección entre el virus de la inmunodeficiencia humana (VIH) y la Leishmaniosis visceral (LV) ha sido descripta de manera reciente, en especial en Brasil y en ciertas áreas de la Europa del Mediterráneo. Los pacientes VIH positivos con fiebre de origen desconocido y/o citopenias tienen indicación de punción aspirativa de médula ósea para estudios microbiológicos e histopatológicos, estos últimos para descartar un síndrome linfoproliferativo. El diagnóstico de leishmaniosis visceral puede confirmarse por diversas técnicas microbiológicas y serológicas: detección de amastigotes de Leishmania en aspirados de médula ósea con tinción de Giemsa, detección de anticuerpos por aglutinación directa, inmunofluorescencia indirecta, detección del antígeno rK39, reacción en cadena de la polimerasa en extendidos de médula ósea y prueba de aglutinación del látex. La LV puede ser la primera manifestación del sida o ser una complicación grave en pacientes ya diagnosticados con VIH e inmunodeficiencia severa. La LV es una complicación grave y potencialmente fatal y debe sospecharse en todo sujeto VIH positivo con fiebre de etiología desconocida y/o citopenias.
The association between visceral leishmaniasis (VL) and HIV is recent and has an increasing number of cases in Brazil and worldwide - especially in the Mediterranean region of Europe. HIV patients with cytopenias and/or fever of an unknown etiology, have indication of bone marrow aspirate for microbiological cultures and histopathological examination to rule out lymphoproliferative disorders. Diagnosis of VL can be confirmed by the following examinations: Leishmania amastigotes detection in bone marrow aspirate with Giemsa smear, direct agglutination test, indirect immunofluorescence, rK39 dipstick test, polymerase chain reaction and latex agglutination test. VL may be the first infection related with HIV or patients can be diagnosed with VL concomitantly with AIDS. HIV/AIDS-associated VL is an aggressive complication with a potentially fatal evolution in advanced HIV/AIDS patients, without specific symptoms, that should be suspected in all HIV subjects with fever of unknown etiology and cytopenias.
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Humanos , Masculino , Persona de Mediana Edad , Serodiagnóstico del SIDA , Leishmaniasis/complicaciones , Punciones , Infecciones por VIH/complicaciones , Enfermedades Endémicas , Leishmaniasis Visceral/diagnósticoRESUMEN
OBJECTIVES: Cuba is a tobacco-producing country that has been economically isolated as a consequence of an embargo imposed by the USA. It has also experienced a severe economic depression in the 1990s after the withdrawal of support by the former Soviet Union. These characteristics provide a unique opportunity to study the relation between large changes in economic activity, cigarette price and demand for cigarettes in a relatively isolated socialist economy. STUDY DESIGN: This is an observational epidemiological study. METHODS: Data were obtained on the annual price of a packet of cigarettes and the mean number of cigarettes consumed per adult living in Cuba from 1980 to 2014. Descriptive and regression analysis were used to explore the relationship between cigarette consumption and price in Cuba. RESULTS: In 1980, the mean price of a packet of cigarettes was 1.53 Cuban peso (CUP) in 1997 prices and the mean annual per capita consumption was 2237 cigarettes. In 2014, the mean price had increased to 5.57 CUP (1997 prices) per packet of cigarettes, and consumption had fallen to 1527 cigarettes per capita. There were significant negative associations between annual cigarette consumption and both price and living through an economic depression. The elasticity was approximately -0.31 with price, and living through an economic depression was also associated with lower consumption of cigarettes (a reduction of 9%, 95% confidence intervals -0.18 to -0.001). CONCLUSIONS: Higher cigarette pricing, along with other public health interventions, are required to protect the national population from the adverse effects of tobacco smoke exposure.
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Fumar Cigarrillos/economía , Comercio/estadística & datos numéricos , Recesión Económica , Productos de Tabaco/economía , Adulto , Fumar Cigarrillos/epidemiología , Cuba/epidemiología , HumanosRESUMEN
Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.
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Antineoplásicos/efectos adversos , Neutropenia Febril/prevención & control , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias/tratamiento farmacológico , Guías de Práctica Clínica como Asunto/normas , Índice de Severidad de la Enfermedad , Adulto , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Neutropenia Febril/inducido químicamente , Neutropenia Febril/diagnóstico , Humanos , Pronóstico , Medición de Riesgo , Sociedades MédicasRESUMEN
We studied the soft landing of Ni atoms on a previously damaged graphene sheet by means of molecular dynamics simulations. We found a monotonic decrease of the cluster frequency as a function of its size, but few big clusters comprise an appreciable fraction of the total number of Ni atoms. The aggregation of Ni atoms is also modeled by means of a simple phenomenological model. The results are in clear contrast with the case of hard or energetic landing of metal atoms, where there is a tendency to form mono-disperse metal clusters. This behavior is attributed to the high diffusion of unattached Ni atoms, together with vacancies acting as capture centers. The findings of this work show that a simple study of the energetics of the system is not enough in the soft landing regime, where it is unavoidable to also consider the growth process of metal clusters.
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The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.
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Anticoagulantes/uso terapéutico , Heparina/uso terapéutico , Neoplasias/tratamiento farmacológico , Ensayos Clínicos como Asunto , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Neoplasias/mortalidad , Tromboembolia Venosa/prevención & control , Vitamina K/antagonistas & inhibidoresRESUMEN
In the context of global climate change where harmful algal blooms (HABs) might become more frequent and more severe, several studies have been conducted on the perturbation of embryonic development of marine animals by microalgal toxins. Okadaic acid (OA) and analogs (DSP toxins) produced by dinoflagellates of the genera Dynophysis and Prorocentrum are known to disturb embryogenesis. This study investigated the impact of dissolved DSP toxin (OA and Dinophysistoxin 1, DTX-1) exposure on embryo development of Longfin yellowtail Seriola rivoliana. Eggs were exposed to different concentrations of dissolved DSP toxins (low treatment: at 120µgl-1 OA eq; high treatment 175µgl-1 OA eq.). The first objective was to study the global toxic effect of DSP toxins with hatching percentages. Secondly, the effect of these toxins was investigated at molecular and functional level by measuring expression of responsible genes for bone morphogenetic protein (BMP) and proliferating cell nuclear antigen (PCNA) measuring phosphatase enzyme (serine/threonine and alkaline phosphatases) activities. Our results showed drastic mortalities induced by DSP toxins in both low and high concentration treatments. Activities of both protein and alkaline phosphatases were significantly inhibited by DSP toxin treatments, whose effects on gene expression were less evident, but levels of BMP expression in eggs treated with the lowest toxin concentration were significantly different from that in the control treatment. This work revealed an embryotoxic effect of DSP toxins resulting in high mortality of eggs. Phosphatase inhibition could have participated in part in these global effects by perturbing the regulation of pathways related to embryogenesis and resulting in a perturbation of gene expression.
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Embrión no Mamífero/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Peces , Ácido Ocadaico/toxicidad , Piranos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Cambio Climático , Dinoflagelados/metabolismo , Inhibidores Enzimáticos , Peces/embriología , Floraciones de Algas NocivasRESUMEN
En la actualidad el país enfrenta grandes cambios referentes a las normas orientadas a la gestión tecnológica que se debe aplicar a los equipos biomédicos, además de grandes cambios que hoy el Subsistema Nacional de Calidad ha presentado, orientados al control metrológico legal que se debe aplicar a algunos equipos que prestan sus servicios en el área de la salud. Dado lo anterior, este trabajo pretende presentar una propuesta basada en un modelo de gestión que integra los requerimientos del control metrológico legal aplicado a los equipos biomédicos, y a su vez la aplicación de procesos de medición para las actividades asociadas a la evaluación de la conformidad, utilizando como metodología un proceso de caracterización de las exigencias establecidas en las normas de Colombia. Estas normas están asociadas al control metrológico legal y a lo establecido en diferentes normas orientadas al aseguramiento de las mediciones en equipos; esto orientado a la evaluación de la conformidad, obteniendo como resultado más significativo una propuesta de estructura de gestión que le permitirá a las unidades de ingeniería de las entidades prestadoras de servicios de salud, no solo cumplir con lo exigido en las normas actuales sino a prestar unos servicios de alta calidad basados en confiabilidad como apoyo a los actividades encaminadas a la seguridad del paciente.
At present, the country faces major changes regarding regulations oriented toward technological management to be applied to biomedical equipment. In addition to those significant changes today, the National Quality System has introduced others regarding metrological control that need to be applied to some equipment in health services. As such, this paper aims to present a proposal based on a management model which integrates legal metrological controls applied to biomedical equipment, along with the application of measurement processes for activities associated to conformity evaluation. This model also uses a method of characterization of requirements established in different regulations aimed at ensuring equipment measurements also oriented toward conformity evaluation. The most significant expected result will be the proposal of a management structure enabling engineering units of health service providers to not only comply with said regulations, but also to offer high quality services based on trustworthiness, as support for activities aimed at patient safety.
Na atualidade o país enfrenta grandes mudanças referentes às normas orientadas à gestão tecnológica que se deve aplicar aos equipamentos biomédicos, além de grandes mudanças que hoje o subsistema nacional de qualidade a apresentado e orientado ao controle metrológico legal que se deve aplicar a alguns equipamentos que prestam seus serviços na área da saúde, dado o anterior este trabalho pretende apresentar uma proposta baseada num modelo de gestão que integra os requerimentos do controle metrológico legal aplicado às equipamentos biomédicos e a sua vez o aplicativo de processos de medida para as atividades associadas à avaliação da conformidade, utilizando como metodologia um processo de caracterização das exigências estabelecidas nas normas da Colômbia associadas ao controle metrológico legal e ao estabelecido em diferentes normas orientadas à garantia das medidas em equipamentos, isto orientado à avaliação da conformidade, obtendo como resultado mais significativo uma proposta de estrutura de gestão que lhe permitirá às unidades de engenharia das entidades prestadoras de serviço de saúde, não só cumprir com o exigido nas normas atuais senão também a emprestar uns serviços de alta qualidade baseados em fiabilidade como apoio às atividades encaminhadas à segurança do paciente.
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BACKGROUND: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. METHODS: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. RESULTS: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. CONCLUSIONS: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.
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Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , MicroARNs/sangre , Anciano , Animales , Biomarcadores/sangre , Diagnóstico Precoz , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Curva ROC , Ratas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The ZNF217 gene, a potential oncogene amplified and overexpressed in several cancers including colorectal cancer (CRC), acts as a transcription factor that activates or represses target genes. The polymorphisms rs16998248 (T>A) and rs35720349 (C>T) in coronary artery disease have been associated with reduced expression of ZNF217. In this study, we analyzed the 2 polymorphisms in Mexican patients with CRC. Genotyping of rs16998248 and rs35720349 sites was performed by polymerase chain reaction-restriction fragment length polymorphism in 203 Mexican Mestizos, 101 CRC patients, and 102 healthy blood donors. Although no statistical differences regarding genotype and allele frequencies of ZNF217 polymorphisms were observed (P > 0.05), linkage disequilibrium was significant in CRC patients (r(2) = 0.39, P < 0.0001), as a result of reduced AC haplotype frequency. Thus, the AC haplotype may protect against CRC.
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Carcinogénesis/genética , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Transactivadores/genética , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Humanos , MéxicoRESUMEN
OBJECTIVE AND DESIGN: Carrageenan-induced paw edema has been described as a local and acute inflammatory process. In fact, little is known about the time course and systemic changes following a carrageenan injection. In this study, we examine the systemic changes that follow carrageenan injection in the paw. METHODS: Acute inflammation was produced by subplantar injection of carrageenan in a hind paw of Sprague-Dawley rats. Saline was used in control rats. Paw volume was measured with a plethysmometer. The hot plate latency test was used to quantify antinociception. C-reactive protein (CRP) levels were measured with a sandwich enzyme immunoassay. Fibrinogen concentration was measured using the gravimetric method. Lung morphometric analysis was performed using an image processing package. Lungs and paws were also examined for tissue factor (TF) and proinflammatory cytokines expression by immunohistochemistry. RESULTS: We found diverse systemic changes including increased levels of acute phase proteins, such as CRP and fibrinogen, and a lung inflammatory process characterized by lung edema, fibrin deposition, and leukocyte infiltration. An elevated expression of TF, IL-6, IL-1ß, and TNFα, was observed in paw and lung tissue sections by immunohistochemical methods. CONCLUSION: This study provides new evidence that a local carrageenan injection induces a systemic response.
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Carragenina , Inflamación/patología , Animales , Proteína C-Reactiva/metabolismo , Citocinas/metabolismo , Edema/inducido químicamente , Edema/patología , Fibrinógeno/metabolismo , Pie/patología , Inflamación/inducido químicamente , Pulmón/patología , Dimensión del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tromboplastina/metabolismoRESUMEN
BACKGROUND: Loss or mutations of the BRCA1 gene are associated with increased risk of breast and ovarian cancers and with prostate cancer (PCa) aggressiveness. Previously, we identified GADD153 as a target of BRCA1 protein, which increases doxorubicin sensitivity in human p53 -/- PCa cells (PC3). Considering that p53 is a crucial target in cancer therapy, in this work we investigated p53 role in the regulation of transcription of GADD153. METHODS: We performed reverse transcription quantitative PCR (RT-qPCR), western blot and luciferase assays to analyze GADD153 and/or BRCA1 expression in response to ultraviolet or doxorubicin exposure in PC3 p53 stable-transfected cells and LNCaP (p53+/+) cells. BRCA1 protein recruitment to GADD153 promoter was studied by chromatin immunoprecipitation-qPCR. To assess expression of BRCA1 and/or p53 target genes, we used a panel of stable-transfected PCa cell lines. We finally analyzed these genes in vivo using BRCA1-depleted PCa xenograft models. RESULTS: We found that GADD153 was highly induced by doxorubicin in PC3 cells; however, this response was totally abolished in LNCaP (p53wt) and in p53-restituted PC3 cells. Furthermore, BRCA1 protein associates to GADD153 promoter after DNA damage in the presence of p53. Additionally, we demonstrated that BRCA1 and/or p53 modulate genes involved in DNA damage and cell cycle regulation (cyclin D1, BLM, BRCA2, DDB2, p21(WAF1/CIP1), H3F3B, GADD153, GADD45A, FEN1, CCNB2), EMT (E-cadherin, ß-catenin, vimentin, fibronectin, slug, snail) and Hedgehog pathways (SHH, IHH, DHH, Gli1, PATCH1). Furthermore, xenograft studies demonstrated that BRCA1 knockdown in PC3 cells increased tumor growth and modulated these genes in vivo. CONCLUSIONS: Although BRCA1 induces GADD153 in a p53 independent manner, p53 abolished GADD153 induction in response to DNA damage. In addition, several important PCa targets are modulated by BRCA1 and p53. Altogether, these data might be important to understand the therapy response of PCa patients.
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Proteína BRCA1/metabolismo , Neoplasias de la Próstata/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Proteína BRCA1/genética , Ciclo Celular/genética , Línea Celular Tumoral , Daño del ADN , Erizos/genética , Erizos/metabolismo , Xenoinjertos , Humanos , Masculino , Ratones , Neoplasias de la Próstata/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Factor de Transcripción CHOP/metabolismo , Transcripción Genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P = 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) = 3.16, 95% confidence interval (95% CI) = 1.41-7.06, P = 0.005) and multivariate models (HR = 3.01, 95% CI = 1.13-8.02, P = 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P = 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR = 3.06, 95% CI = 1.20-7.80, P = 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
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Predisposición Genética a la Enfermedad/genética , Glutatión Transferasa/genética , Recurrencia Local de Neoplasia/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Anciano , Estudios de Casos y Controles , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Prostatectomía , Neoplasias de la Próstata/cirugía , Factores de RiesgoRESUMEN
The most commonly used drugs against pain act by inhibiting the cyclooxygenases (COXs). Metamizol (dipyrone) inhibits the COXs and is widely used in Europe and Latin America as a non-opioid analgesic. One target of metamizol and other non-opioid analgesics is the periaqueductal grey matter (PAG), where they trigger descending inhibition of spinal nociceptive transmission. Also, cannabinoids exert an analgesic action at several structures in the peripheral and central nervous system, including the PAG. The present study investigates whether the antinociceptive action of metamizol in the lateral-ventrolateral (LVL) PAG during inflammation is related to endocannabinoids. In anaesthetized rats, unitary action potentials were recorded from spinal nociceptive neurons with receptive fields in the ipsilateral hind paw. Inflammation of the paw induced neuronal hyperexcitability, which was attenuated by intra-LVL-PAG microinjection of metamizol either at the beginning of inflammation or when hyperexcitability was fully established. In both cases, the antinociceptive effect of metamizol was reduced by a microinjection of AM251, an antagonist at the CB1 cannabinoid receptor, either into the LVL-PAG or into the rostral ventromedial medulla (RVM). The RVM is a downstream structure that funnels PAG-derived descending inhibition into the spinal cord. These results show that endocannabinoids and their CB1 receptor (1) contribute at the LVL-PAG to the antinociceptive effects of metamizol, and possibly other non-opioid analgesics; and (2) participate in the PAG-derived activation of RVM descending antinociceptive influences.
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Antiinflamatorios no Esteroideos/uso terapéutico , Moduladores de Receptores de Cannabinoides/metabolismo , Dipirona/uso terapéutico , Endocannabinoides , Hiperalgesia/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Bulbo Raquídeo/efectos de los fármacos , Sustancia Gris Periacueductal/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Dipirona/farmacología , Hiperalgesia/metabolismo , Inflamación/metabolismo , Masculino , Bulbo Raquídeo/metabolismo , Microinyecciones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Nociceptores/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/antagonistas & inhibidoresRESUMEN
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5ß1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy.
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Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/farmacología , Neovascularización Patológica/tratamiento farmacológico , Neoplasias de la Próstata/irrigación sanguínea , Análisis de Varianza , Animales , Cartilla de ADN/genética , Hemo-Oxigenasa 1/metabolismo , Técnicas Histológicas , Humanos , Inmunohistoquímica , Luciferasas , Masculino , Ratones , Ratones Desnudos , Neovascularización Patológica/patología , Plásmidos/genética , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular/metabolismoRESUMEN
INTRODUCTION: Neurocysticercosis (NC) is the most prevalent parasitic infection in the CNS. Its frequency in our environment has increased with migratory movements. The clinical and demographic characteristics of patients with NC attended in a third level hospital in an area with a high prevalence of immigrant have been analyzed. PATIENTS AND METHODS: A retrospective study was done of the patients registered by the Coding Service of Virgen de la Arrixaca Hospital (January 2996 to December 2009), analyzing all the clinical histories of patients discharged with the primary or secondary diagnosis of neurocysticercosis. The most relevant epidemiological, diagnostic and therapeutic data were analyzed. RESULTS: 35 patients were included in the study. Of these, 24 were men, all coming from Latin America. The most prevalent onset was seizure episode (27 patients). The number of cases per year began to increase after 2002. Although only 21 of the cases had criteria to begin medical treatment with albendazole, it had been prescribed to 29 patients. CONCLUSION: In Murcia, NC is mainly an imported disease. An increase in the annual incidence has been observed since 2002, parallel to the rise in the number of immigrants. Approximately 25% of the patients received treatment in spite of not having antiparasitic treatment indication.