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1.
Clin Transl Oncol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266875

RESUMEN

Theragnostic is a type of precision medicine that uses molecules linked to radioactive isotopes for the diagnosis and treatment of diseases. In recent years, it has gained significant importance to treat neuroendocrine tumors and is currently being used in prostate cancer. Various radiopharmaceuticals have emerged for diagnosing and detecting lesions showing prostate-specific membrane antigen (PSMA) positivity on the Positron emission tomography/computed tomography scan, being the most widely used labeled with [68Ga] and [18F]. Its use as therapy in prostate cancer (PC) has been assessed in the VISION, TheraP, and PSMAfore clinical trials conducted with the radioligand [177Lu]Lu-PSMA-617, demonstrating significant antitumor activity. The aim of this article is to present practical recommendations, based on current available scientific evidence and on a multidisciplinary consensus, for the diagnosis and treatment with [177Lu]Lu-PSMA-617 in patients with PC.

2.
One Health ; 18: 100746, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38746539

RESUMEN

Multi-host communities are perfect scenarios for the emergence and spread of pathogens, threatening the recovery of endangered, isolated, or inbred populations, such as the brown bear (Ursus arctos) in northwestern Spain. The population recovery in recent years has forced bears to occupy highly anthropized areas, increasing their interaction with human and domestic animals, with potential consequences for global health. During 2022-2023 a survey of parasites, bacteria and viruses shared between wildlife, domestic animals and humans was performed in this population using non-invasive surveillance, i.e., bear fecal samples (n = 73) and sponge-based sampling of trees (n = 42; 14 rubbed trees and 28 control trees). Pathogen detection rates were defined as the percentage of qPCR or culture-positive samples. Generalized linear models were fitted to assess their relationship with environmental variables including dispersion of the human population, and percentage of agricultural and periurban habitats in a 6 km-buffer around each sample. Canine Adenovirus type 1 (45.2%), Giardia spp. (15.1%), Salmonella spp. (12.3%), and extended-spectrum-beta-lactamases (ESBL) Escherichia coli (1.4%) were identified in fecal samples. In contrast, only five sponges from three rubbed and two control trees resulted positive to E. coli (14.3%). The results suggest that several pathogens are common in the Cantabrian brown bear population and that anthropization of the territory modulates their prevalence and richness. The effective design of management programs for bear conservation will require a one-health approach, in which genetic analysis of non-invasive samples can be key tools for the sanitary surveillance at the wildlife-livestock-human interface.

3.
Front Oncol ; 14: 1385466, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774416

RESUMEN

Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. Patients and methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.

4.
Ginecol. obstet. Méx ; Ginecol. obstet. Méx;92(4): 137-144, ene. 2024. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1557867

RESUMEN

Resumen OBJETIVO: Determinar la incidencia del espectro del acretismo placentario en pacientes ingresadas a la unidad de cuidados intensivos obstétricos del Hospital de la Mujer, Culiacán, Sinaloa. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo fundamentado en el análisis de la base de datos del Hospital de la Mujer de pacientes internadas entre los años 2017 a 2020 con diagnóstico de espectro de placenta acreta, referidas o diagnosticadas en la institución e intervenidas para histerectomía por la complicación estudiada. RESULTADOS: Se analizaron 22 pacientes con diagnóstico de acretismo placentario que dieron una incidencia de 0.09%; de éstas, a 1 se le indicó cesárea; 19 de las 22 pacientes tenían antecedente de cicatriz uterina previa, todas con placenta previa. El promedio de edad fue de 30.86 ± 4 años. La cesárea se practicó, en promedio, a las 34 semanas de embarazo con dos técnicas quirúrgicas. El sangrado promedio estimado fue de 1.947 mL. Las complicaciones transoperatorias fueron las lesiones: ureteral (n = 2) y vesical (n = 1). La principal complicación posoperatoria fue la fístula vesicouterina (n = 1). El promedio de estancia fue de 2 días en 16 de las 22 pacientes y de 7 días en las 6 restantes. CONCLUSIONES: Lo importante del acretismo placentario es el diagnóstico oportuno que permita derivar a las pacientes a centros hospitalarios que cuenten con especialistas experimentados en la atención de estos casos.


Abstract OBJECTIVE: To determine the incidence of placental accretism spectrum in pregnant women admitted to the obstetric intensive care unit of the Hospital de la Mujer, Culiacán, Sinaloa. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive study based on the analysis of the database of the Hospital de la Mujer of patients admitted between 2017 and 2020 with a diagnosis of placenta accreta spectrum, referred or diagnosed at the institution and underwent hysterectomy for the complication studied. RESULTS: Twenty-two patients with a diagnosis of placenta accreta were analysed, giving a prevalence of 0.09%; of these, caesarean section was indicated in 0.2%. 19 of the 22 patients had a history of previous uterine scarring, all with placenta praevia. Mean age was 30.86 ± 4 years. Caesarean section was performed at a mean gestational age of 34 weeks using two surgical techniques. The mean estimated blood loss was 1,947 mL. The most common operative complications were ureteral (n = 2) and bladder (n = 1) injuries. The most common postoperative complication was vesico-uterine fistula (n = 1). The mean length of stay was 2 days in 16 of the 22 patients and 7 days in the remaining 6 patients. CONCLUSIONS: The most important aspect of placenta accreta is early diagnosis, which allows referral to hospital centres with specialists experienced in the management of these cases.

5.
Heliyon ; 9(6): e17011, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37484216

RESUMEN

Dolphins are marine mammals that often live in coastal habitats. Common causes of severe skeletal disorders among wild dolphins are congenital vertebral anomalities, collisions with sea vessels, trauma, hunting-related injury, infectious diseases, environmental pollution, and tumors. A free-ranging male, 3-year-old common dolphin (Delphinus delphis) was found dead in the coast of Asturias in northern Spain. Postmortem examination revealed lordosis in the caudal vertebral column, while X-ray imaging and computer tomography showed well-organized palisade-like periosteal proliferation, appearing as florid-like accretions, along the spinous apophysis of 26 lumbar-caudal vertebrae. The transverse apophysis was affected on only a few caudal vertebrae. The cortical layer remained intact. Histology of vertebra tissue showed periosteal proliferation of cancellous bone. The animal was diagnosed with hypertrophic osteopathy. The lungs showed diffuse parasitic granulomatous bronchointerstitial pneumonia caused by Halocercus delphini, consolidation of the pulmonary tissue, congestion, and alveolar edema. The animal was also afflicted by parasitic granulomatous gastritis caused by Anisakis simplex sensu lato and tattoo skin disease. The dolphin suffered from hypertrophic osteopathy associated with pulmonary Halocercus delphini infestation. This syndrome, known as hypertrophic pulmonary osteopathy, has been described in diverse terrestrial mammals, including domestic animals, wildlife and humans, but not in dolphins. This case reports the first description of hypertrophic osteopathy associated to a pulmonary disorder in dolphin, and it provides insights into factors that can induce column malformation in dolphins, suggesting the importance of taking thoracic lesions into account during differential diagnosis.

6.
Texto & contexto enferm ; 32: e20230075, 2023. tab
Artículo en Inglés | LILACS-Express | LILACS, BDENF - Enfermería | ID: biblio-1530564

RESUMEN

ABSTRACT Objective: to understand the health promotion practices developed by nurses in the Primary Care context in Florianópolis and Girona. Method: this is a comparative study with a qualitative approach and of the descriptive exploratory type, carried out with eight nurses between June 2021 and April 2022 in health units that developed health promotion practices. The data, collected by means of semi-structured interviews, were analyzed through thematic analysis based on the health promotion framework. Results: four categories related to health promotion practices emerged from the data, namely: Training actions for health professionals in health promotion; Health promotion activities in individual consultations; Health education group activities; and Community health promotion actions. Conclusion: it is concluded that, in both municipalities, nurses develop individual and collective health promotion practices through groups and community actions, focusing on lifestyle changes. In Florianópolis they are grounded on the National Health Promotion Policy and, in Girona, health promotion actions are based on actions involving specific groups aimed at preventing diseases.


RESUMEN Objetivo: comprender las prácticas de promoción de la salud desarrolladas por enfermeros en el contexto de Atención Primaria de Florianópolis y Girona. Método: estudio comparativo de enfoque cualitativo y del tipo exploratorio-descriptivo, realizado entre junio de 2021 y abril de 2022 con ocho enfermeros en unidades de salud que desarrollaban prácticas de promoción de la salud. Los datos, recolectados por medio de entrevistas semiestructuradas, fueron analizados a través de análisis temático sobre la base del referencial de la promoción de la salud. Resultados: cuatro categorías relacionadas con las prácticas de promoción de la salud surgieron de los datos, a saber: Acciones para la formación de profesionales de la salud en promoción de la salud; Actividades de promoción de la salud en consultas individuales; Actividades grupales de educación en salud; y Acciones comunitarias de promoción de la salud. Conclusión: se concluye que, en ambos municipios, los enfermeros desarrollan prácticas individuales y colectivas de promoción de la salud por medio de grupos y acciones comunitarias, con énfasis en modificar estilos de vida. En Florianópolis se fundamentan en la Política Nacional de Promoción de la Salud y, en Girona, las acciones de promoción de la salud se basan en actividades relacionadas con grupos específicos dirigidos a prevenir enfermedades.


RESUMO Objetivo: compreender as práticas de promoção da saúde desenvolvidas por enfermeiros no contexto da Atenção Primária de Florianópolis e Girona. Método: trata-se de um estudo comparativo, de abordagem qualitativa, do tipo exploratório descritivo, realizado em unidades de saúde que desenvolviam práticas de promoção da saúde, com oito enfermeiros, no período entre junho de 2021 a abril de 2022. Os dados, coletados por entrevistas semiestruturadas, foram analisados por meio de análise temática com base no referencial da promoção da saúde. Resultados: emergiram dos dados quatro categorias relacionadas às práticas de promoção da saúde: Ações de formação de profissionais de saúde em promoção da saúde; Atividades de promoção da saúde na consulta individual; Atividades grupais de educação em saúde; Ações comunitárias de promoção da saúde. Conclusão: conclui-se que em ambos os municípios os enfermeiros desenvolvem práticas de promoção da saúde individuais e coletivas por meio de grupos e ações comunitárias, com enfoque na mudança de estilos de vida. Em Florianópolis estão fundamentadas na Política Nacional de Promoção da Saúde e, em Girona, as ações de promoção da saúde estão baseadas nas ações envolvendo grupos específicos voltados para a prevenção da doença.

7.
Ginecol. obstet. Méx ; Ginecol. obstet. Méx;91(9): 706-710, ene. 2023. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1520962

RESUMEN

Resumen ANTECEDENTES: Las quemaduras son la forma más severa de estrés que el cuerpo puede sufrir; pueden generarse por diferentes agentes térmicos y químicos. CASO CLÍNICO: Paciente de 25 años, con dolor intenso en la región genital de 12 horas de evolución, secundario a la introducción en la vagina de una piedra de alumbre. Se le hicieron múltiples irrigaciones con solución salina al 0.9% sin obtener el resto de la piedra de alumbre. Se le aplicó sulfadiazina de plata en la cavidad vaginal cada 12 horas, óvulos vaginales de ketanserina, miconazol y metronidazol cada 8 horas, ketorolaco por vía oral 10 mg cada 8 horas. Durante su estancia hospitalaria tuvo buena evolución, con disminución de la inflamación en la zona genital, epitelización adecuada. Al tercer día se dio de alta del hospital con cita para valoración a los siete días. CONCLUSIÓN: El tratamiento de las quemaduras en el área genital, por agentes químicos, tiene como piedra angular la identificación del agente causante de la lesión que permita actuar de forma inmediata y evitar las secuelas físicas, sexuales y psicológicas mediante el lavado exhaustivo con solución o agua estéril para remover el agente causal y disminuir que continúe actuando en el sitio afectado.


Abstract BACKGROUND: Burns are the most severe form of stress that the body can suffer; they can be caused by various thermal and chemical agents. CLINICAL CASE: A 25-year-old female patient presented with severe genital pain of 12 hours' duration, secondary to the introduction of an alum stone into the vagina. She underwent several irrigations with 0.9% saline without obtaining the rest of the alum stone. She was given vaginal silver sulfadiazine every 12 hours, vaginal ketanserin, miconazole and metronidazole every 8 hours and oral ketorolac 10 mg every 8 hours. During her stay in hospital, she progressed well, with a decrease in genital inflammation and adequate epithelialisation. She was discharged on the third day with an appointment for a seven-day follow-up. CONCLUSION: The management of genital burns caused by chemical agents is based on the identification of the agent causing the lesion, which allows immediate action and prevents physical, sexual and psychological sequelae by thorough washing with sterile solution or water to remove the causative agent and reduce its continued action in the affected area.

8.
Infect Dis (Lond) ; 54(11): 810-818, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35854671

RESUMEN

BACKGROUND: COVID-19 may trigger an acute hyperinflammatory syndrome characterised by heightened levels of acute phase reactants and is associated with adverse outcomes among hospitalised individuals. The relationship between 48-hour changes in acute phase reactants and adverse outcomes is unclear. This study evaluated the relationship between change in four acute phase reactants (interleukin-6, procalcitonin, ferritin, and C-reactive protein), and the risk for in-hospital death and invasive mechanical ventilation. METHODS: A retrospective cohort among 2,523 adult patients hospitalised with COVID-19 pneumonia was conducted. Changes in IL-6, procalcitonin, ferritin, and CRP from admission to 48 h after admission were recorded. Delta was calculated using the difference in each acute phase reactant at admission and at 48-hours. Delta in acute phase reactants and the risk for in-hospital death and invasive mechanical ventilation was assessed using logistic regression models adjusting for demographics and comorbidities. RESULTS: Patients with both admission and 48-hour measurement for interleukin-6 (IL-6) (n = 541), procalcitonin (n = 828), ferritin (n = 1022), and C-reactive protein (CRP) (n = 1919) were included. Baseline characteristics were similar across all four populations. Increases in ferritin associated with a heightened risk of in-hospital death (OR 1.00032; 95%CI 1.00007- 1.00056; p < .001) and invasive mechanical ventilation (OR 1.00035; 95%CI 1.00014- 1.00055; p = .001). Therefore, for every 100 ng/mL increase in ferritin, the odds for in-hospital death and invasive mechanical ventilation increase by 3.2% and 3.5%, respectively. CONCLUSIONS: Delta in ferritin is associated with in-hospital death and invasive mechanical ventilation. Other acute phase reactants were not associated with these outcomes among COVID-19 inpatients.


Asunto(s)
COVID-19 , Adulto , Proteína C-Reactiva , COVID-19/terapia , Ferritinas , Mortalidad Hospitalaria , Humanos , Interleucina-6 , Polipéptido alfa Relacionado con Calcitonina , Respiración Artificial , Estudios Retrospectivos , SARS-CoV-2
9.
Nurs Rep ; 12(2): 291-303, 2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35466249

RESUMEN

Nurses' lifestyle habits play a key role in promoting healthy lifestyles; although, they may not always be entirely healthy and can be influenced by working conditions. This paper aims to analyze the influence of doing shift work on nurses' lifestyle habits. Participants (n = 219) were recruited from 27 primary health care centres in Spain. Data were collected on socio-demographic characteristics, working conditions and lifestyle behaviour, assessed by use of an adhoc questionnaire including validated measures. Descriptive analysis and logistic regression models were performed. A total of 95% of the nurses reported having an adequate diet; 45.2% did not engage in any type of physical activity; and 85.8% did not smoke, especially women. A total of 60.3% did shift work, especially the younger ones (80.8%; p < 0.001), these nurses being the ones with the worst food habits (81.8%). In contrast, nurses who did shift work, exercised more days a week (69.5%; p < 0.001). The dietary habits of the nurses were adequate. Low tobacco consumption and low adherence to physical activity were observed, especially among women. Shift work harmed eating habits and obesity rates, but was a protective factor in terms of adherence to physical exercise.

10.
Arch. argent. pediatr ; 120(2): e71-e74, abril 2022. tab, ilus
Artículo en Español | LILACS, BINACIS | ID: biblio-1363967

RESUMEN

Las intoxicaciones medicamentosas son un motivo de consulta frecuente en pediatría, además de una de las principales causas externas de mortalidad en adolescentes. El diagnóstico y tratamiento tempranos son fundamentales para el manejo adecuado de estos casos. Se presenta una niña de 13 años que, luego de ingerir un fármaco desconocido, muestra decaimiento y manifestaciones clínicas gastrointestinales. Por sospecha de intoxicación con hierro y la imposibilidad de determinar los niveles de sideremia de manera urgente, se realiza radiografía de abdomen, que confirma el diagnóstico y permite el tratamiento adecuado de la paciente. En este caso, se destaca la utilidad de la radiología para el diagnóstico en la sospecha de intoxicación con hierro, gracias a la radiopacidad de sus sales


Drug intoxication is a common reason for pediatric emergency department (ED) visits and one of the leading causes of death among teenagers. Early diagnosis and treatment are essential for a proper management of these patients. We present a 13-year-old girl attended at the ED showing excessive sleepiness and gastrointestinal symptoms after taking an unknown drug. Due to suspected iron overdose and the impossibility of measuring urgent iron levels, an abdominal X-ray was performed, which confirmed the diagnosis. We highlight the utility of radiology in the diagnosis of iron poisoning, which is possible due to its radiopacity.


Asunto(s)
Humanos , Femenino , Adolescente , Servicio de Urgencia en Hospital , Hierro , Intoxicación , Rayos X
11.
Lima; Organismo Andino de Salud Convenio Hipólito Unanue; 103; 27 ene, 2022. 3 p.
No convencional en Español | LILACS, LIPECS | ID: biblio-1381217

RESUMEN

Webinar N° 103 del ORAS-CONHU, realizado el 27 de enero de 2022, Oxfam presentó el informe "Las desigualdades matan. Se requieren medidas sin precedentes para acabar con el inaceptable aumento de las desigualdades por la COVID-19". Conferencistas del webinar: Carlos Mejía, Director Ejecutivo Oxfam Colombia, Gloria García, Directora Regional de Programas e Influencia Oxfam en América Latina y Ernesto Rodríguez, Consultor ORAS-CONHU, Director del Centro Latinoamericano sobre Juventud.


Asunto(s)
Factores Socioeconómicos , Perú , Venezuela , Bolivia , Colombia , Infecciones por Coronavirus , Ecuador , COVID-19
12.
Edumecentro ; 14: e2201, 2022. tab, graf
Artículo en Español | LILACS | ID: biblio-1404644

RESUMEN

RESUMEN Fundamento: José Martí, Héroe Nacional de Cuba, consideraba que la medicina era como el derecho, profesión de lucha, y que se necesitaba un alma bien templada para desempeñar con éxito ese sacerdocio. Objetivo: diseñar un sistema de aplicaciones interactivas para segundo año de la carrera de Medicina con vistas a profundizar en la relación que tuvo José Martí con las ciencias médicas. Métodos: se realizó una investigación de desarrollo en el periodo septiembre-diciembre de 2018 en la Facultad de Ciencias Médicas de Bayamo, Cuba. Se utilizaron métodos teóricos y empíricos: revisión documental y cuestionario a estudiantes. Resultados: se confeccionó una herramienta efectiva para el conocimiento sobre José Martí y su relación con las ciencias médicas; antes de aplicar el sistema, la mayoría de los estudiantes del grupo control reflejaron un bajo nivel de conocimientos y poca motivación sobre esta temática; resultado que fue revertido después de aplicarlo, cuando la mayoría de los alumnos del grupo experimental alcanzó buenas calificaciones y se sintieron motivados por este tema. Conclusiones: el sistema de aplicaciones interactivas sobre los aspectos relacionados con José Martí y la medicina obtuvo valoraciones muy positivas por los expertos e influyó en el incremento del conocimiento y la motivación en los estudiantes, quienes mostraron una aceptación excelente por esta innovación tecnológica.


ABSTRACT Background: José Martí, National Hero of Cuba, considered that medicine was like law, a fighting profession, and that a well-tempered soul was needed to carry out this priesthood successfully. Objective: to design a system of interactive applications for the second year of Medicine with a view to deepening the relationship that José Martí had with medical sciences. Methods: a development research was carried out from September to December 2018 at the Faculty of Medical Sciences of Bayamo, Cuba. Theoretical and empirical methods were used: documentary review and student questionnaire. Results: an effective tool for knowledge about José Martí and his relationship with medical sciences was created; Before applying the system, most of the students in the control group reflected a low level of knowledge and little motivation on this subject; a result that was reversed after applying it, when most of the students in the experimental group achieved good grades and felt motivated by this topic. Conclusions: the system of interactive applications on aspects related to José Martí and medicine obtained very positive evaluations by the experts and influenced the increase of knowledge and motivation in the students, who showed an excellent acceptance for this technological innovation.


Asunto(s)
Estudiantes de Medicina , Aplicaciones de la Informática Médica , Proyectos de Tecnologías de Información y Comunicación , Educación Médica
13.
Artículo en Inglés | MEDLINE | ID: mdl-34886527

RESUMEN

BACKGROUND: Fibromyalgia is a chronic and complex disease whose management by patients requires a high level of commitment. Patient empowerment therefore represents an important milestone in chronic disease treatment and control. We explored the impact of a peer social support network from the perspective of women with fibromyalgia. METHODS: A generic qualitative design was proposed for the study, for which women who had been diagnosed with fibromyalgia were purposefully selected. Six semi-structured interviews were conducted, and the collected data were thematically analysed. RESULTS: Three key themes emerged regarding the peer social support network: (1) empowerment (facilitating acceptance of the diagnosis and acting as a source of information); (2) effects on well-being and quality of life (attenuated the stigma, improved physical well-being, provided emotional support and was a socialization medium); and (3), valuable aspects (transmitted feelings of being understood and listened to and increased personal feelings of satisfaction). CONCLUSIONS: A peer social support network for women with fibromyalgia exerts positive effects on their physical, mental, and social well-being and empowers them to better manage their disease. Healthcare for women with fibromyalgia should include strategies that connect them through peer social support networks.


Asunto(s)
Fibromialgia , Femenino , Humanos , Grupo Paritario , Investigación Cualitativa , Calidad de Vida , Apoyo Social
14.
Bioorg Med Chem ; 37: 116093, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33773393

RESUMEN

We discovered 6-substituted thieno[2,3-d]pyrimidine compounds (3-9) with 3-4 bridge carbons and side-chain thiophene or furan rings for dual targeting one-carbon (C1) metabolism in folate receptor- (FR) expressing cancers. Synthesis involved nine steps starting from the bromo-aryl carboxylate. From patterns of growth inhibition toward Chinese hamster ovary cells expressing FRα or FRß, the proton-coupled folate transporter or reduced folate carrier, specificity for uptake by FRs was confirmed. Anti-proliferative activities were demonstrated toward FRα-expressing KB tumor cells and NCI-IGROV1 ovarian cancer cells. Inhibition of de novo purine biosynthesis at both 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and glycinamide ribonucleotide formyltransferase (GARFTase) was confirmed by metabolite rescue, metabolomics and enzyme assays. X-ray crystallographic structures were obtained with compounds 3-5 and human GARFTase. Our studies identify first-in-class C1 inhibitors with selective uptake by FRs and dual inhibition of enzyme targets in de novo purine biosynthesis, resulting in anti-tumor activity. This series affords an exciting new platform for selective multi-targeted anti-tumor agents.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Fosforribosilaminoimidazolcarboxamida-Formiltransferasa/antagonistas & inhibidores , Fosforribosilglicinamida-Formiltransferasa/antagonistas & inhibidores , Pirimidinas/farmacología , Tiofenos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Células CHO , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cricetulus , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Receptores de Folato Anclados a GPI/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Fosforribosilaminoimidazolcarboxamida-Formiltransferasa/metabolismo , Fosforribosilglicinamida-Formiltransferasa/metabolismo , Unión Proteica , Pirimidinas/síntesis química , Pirimidinas/metabolismo , Relación Estructura-Actividad , Tiofenos/síntesis química , Tiofenos/metabolismo
15.
J Pediatr Hematol Oncol ; 43(4): e457-e461, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33031162

RESUMEN

INTRODUCTION: During the administration of antineoplastic drugs, acute complications because of toxicity occur, determining their hospital readmission, visits to the emergency department, use of antimicrobials, and possibilities of presenting systemic infections, impacting on their life quality. METHODS: Through a prospective cohort, 60 children with acute lymphoblastic leukemia were followed-up for 30 days after the hospital discharge because of chemotherapy administration, those patients were previously included in a single-blinded study in which 30 (group 1) received Lactobacillus rhamnosus GG probiotic during the administration of chemotherapy. The remaining 30 patients did not receive probiotics (group 2). There were evaluated gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distension, meteorism, constipation, nausea, and vomit, development of infections, antibiotic use, number of emergency department visits, number of hospitalizations, and sepsis diagnosis. STATISTICAL ANALYSIS: To assess the impact of the use of probiotics, the difference in proportions between both study groups was evaluated. RESULTS: Gastrointestinal manifestations (nausea, vomiting, diarrhea, constipation) occurred in 30% of patients in group 1 versus 63% of group 2 (P=0.009). Nine of 30 patients (30.0%) in group 1 went to the emergency room, versus 33.3% of group 2 (P=0.7). Antimicrobials were used in 8 subjects (26.6%) in group 1 versus 6 subjects (53.3%) in group 2 (P=0.03) suspected of an infectious disease. Four (13.3%) group 1 patients were hospitalized versus 30% of group 2 (P=0.1). Two subjects (6.6%) in group 1 had sepsis versus 7 (23.3%) in group 2 (P=0.07).Conclusions:The results indicate that the use of probiotics can be a great alternative in the improvement of gastrointestinal symptoms and the adverse effects associated with chemotherapy.


Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Probióticos/uso terapéutico , Antineoplásicos/uso terapéutico , Niño , Diarrea/inducido químicamente , Diarrea/prevención & control , Femenino , Humanos , Lacticaseibacillus rhamnosus/fisiología , Masculino , Náusea/inducido químicamente , Náusea/prevención & control , Estudios Prospectivos , Vómitos/inducido químicamente , Vómitos/prevención & control
16.
J Pediatr Gastroenterol Nutr ; 71(1): 59-63, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32044834

RESUMEN

OBJECTIVES: The aim of the study was to describe diagnostic criteria used in children with coeliac disease (CD) and selective IgA deficiency; to determine if the publication of the 2012 ESPGHAN criteria prompted any changes; to evaluate the evolution of serological markers. METHODS: Multicenter, retrospective, descriptive study of a cohort of children under 15 years with selective IgA deficiency diagnosed with CD (January 2006 to December 2016). Demographic, clinical, genetic, histological and IgG-based antibodies were collected at diagnosis and follow-up. RESULTS: Eighty-six children were included, 60 diagnosed after the guide. Two groups were established: G1 (n = 63) and G2 (n = 23) with or without diagnostic biopsy respectively. In G1: 87.3% were symptomatic, 87.3% had human leukocyte antigan (HLA) DQ2/DQ8 typing (all positive), all had IgG serology positive (71.5% ATG, 35% EMA, 19% DPG, 9.5% AGA), and all had villous atrophy (Marsh-Oberhuber 2-3). Follow-up data were available in 58 children, 34 after 2 years on a gluten-free diet. Fifty-two percentage remained ATG IgG-positive despite good dietary adherence and symptom remission. Regarding G2: all were diagnosed post-2012, had typical symptoms, HLA DQ2/DQ8 positive and ATG IgG × 10 ULN. Additionally, EMA IgG was performed in 14 (60%), all positive. CONCLUSIONS: In our cohort of children with selective IgA deficiency and diagnosed with CD, children without a diagnostic biopsy suggests that IgG serology was considered the equivalent as IgA isotype, even when this is not addressed in the aforementioned guidelines. Great heterogeneity was observed in the IgG serology used at diagnosis. After 2 years of a gluten-free diet, half of children remained with a positive serology.


Asunto(s)
Enfermedad Celíaca , Deficiencia de IgA , Autoanticuerpos , Biopsia , Enfermedad Celíaca/diagnóstico , Niño , Estudios de Seguimiento , Humanos , Deficiencia de IgA/complicaciones , Deficiencia de IgA/diagnóstico , Inmunoglobulina A , Estudios Retrospectivos , Transglutaminasas
17.
Cell Signal ; 53: 281-293, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30352252

RESUMEN

Conjugated linoleic acid (CLA) constitutes a group of isomers derived from linoleic acid. Diverse studies have suggested that these unsaturated fatty acids have beneficial effects on human health. However, it has also been reported that their consumption can generate alterations in hepatic tissue. Thus, in the present study, we evaluated the effect of two of the major isomers of CLA, cis-9, trans-11-CLA and trans-10, cis-12-CLA, in the regulation of insulin signaling in a hepatic cell model, clone 9 (C9). We found that the two isomers decrease insulin-stimulated phosphorylation of the main proteins involved in insulin signaling, such as Akt at Ser473 and Thr308, the insulin receptor at Tyr1158, IRS-1 at Tyr632, and GSK-3 at Ser9/21. Protein expression, however, was unaffected. Interestingly, both isomers of CLA promoted phosphorylation and activation of PKCε. Inhibition of PKCε activity by a dominant-negative form or knockdown of endogenous PKCε prevented the adverse effects of CLA isomers on insulin-induced Akt phosphorylation. Additionally, we also found that both isomers of CLA increase phosphorylation of IRS-1 at Ser612, a mechanism that probably underlies the inhibition of IRS-1 signaling by PKCε. Using confocal microscopy, we found that both isomers of CLA induced lipid accumulation in C9 cells with the presence of spherical cytosolic vesicles, suggesting their identity as neutral lipid droplets. These findings indicate that cis-9, trans-11-CLA and trans-10, cis-12-CLA isomers could have a significant role in the development of insulin resistance in hepatic C9 cells through IRS-1 serine phosphorylation, PKCε activation, and hepatic lipid accumulation.


Asunto(s)
Resistencia a la Insulina , Ácidos Linoleicos Conjugados/metabolismo , Hígado/citología , Proteína Quinasa C-epsilon/metabolismo , Animales , Línea Celular , Activación Enzimática , Insulina/metabolismo , Isomerismo , Hígado/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas
18.
Actual. nutr ; 19(3): 95-100, Septiembre 2018.
Artículo en Español | LILACS | ID: biblio-970130

RESUMEN

La hiperglucemia es una alteración de las cifras de glucosa reportada frecuentemente por el personal de enfermería en los pacientes hospitalizados que representa un factor de riesgo para diferentes entidades patológicas, como el infarto de miocardio, infarto cerebral, sepsis, infecciones nosocomiales, insuficiencia cardíaca y renal, además de ser una complicación de difícil manejo por la falta de protocolos apropiados. Para ello, existen diferentes tipos de insulina de los cuales debe conocerse su farmacocinética y posología para el tratamiento de las hiperglucemias intrahospitalarias. El esquema que se emplea con mayor frecuencia es el de insulina rápida, utilizando la regla de 2UI de insulina rápida por cada 50 mg/dL de glucosa por arriba de 150 mg/dL.


Asunto(s)
Humanos , Pacientes , Atención Hospitalaria , Hospitales , Hiperglucemia , Insulina
19.
Nutr Cancer ; 70(4): 663-670, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29697274

RESUMEN

INTRODUCTION: Head and neck cancer patients are at high risk of anorexia-cachexia syndrome and literature shows that Eicosapentaenoic acid (EPA) could regulate it. We aim to determine the EPA effect on body composition and pro-inflammatory markers in patients with head neck cancer. MATERIALS AND METHODS: A randomized single-blind placebo-controlled clinical trial was conducted in patients with head and neck squamous cell cancer who received a polymeric diet with 2 g of EPA or a standard polymeric diet for six weeks before antineoplastic treatment. We assessed body composition by bioelectrical impedance analysis and determined IL-1ß, IL-6, TNF-α and IFN-γ, CRP, serum proteins, and blood count at baseline and at the end of the study. RESULTS: 32 patients received EPA (2 g/day) and 32 became controls. A decrease in serum levels of IL-1ß, IL-6, TNF-α, and IFN-γ was observed in the experimental group, as well as regulation of body weight (-0.3 ± 5.9 vs. -2.1 ± 3.7), lean body mass (-0.2 ± 3.8 vs. -1.3 ± 3.6), body fat mass (0.2 ± 3.5 vs. -1.2 ± 3.8), and quality of life (10 ± 33 vs. 5 ± 34). CONCLUSION: Supplementing with 2 g/day of EPA to head and neck cancer patient during antineoplastic treatment regulates serum pro-inflammatory cytokines, body weight, lean body mass, and improve quality of life.


Asunto(s)
Composición Corporal/efectos de los fármacos , Ácido Eicosapentaenoico/farmacología , Neoplasias de Cabeza y Cuello/complicaciones , Inflamación/prevención & control , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Adulto , Anciano , Biomarcadores/análisis , Peso Corporal/efectos de los fármacos , Suplementos Dietéticos , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inflamación/metabolismo , Interferón gamma/sangre , Interleucina-8/sangre , México , Persona de Mediana Edad , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia
20.
Neoplasia ; 20(5): 524-532, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29626752

RESUMEN

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.


Asunto(s)
Tumor Desmoplásico de Células Pequeñas Redondas/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Tumor Desmoplásico de Células Pequeñas Redondas/metabolismo , Humanos , Imidazoles , Masculino , Ratones , Piridinas , Pirimidinas , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Sarcoma/tratamiento farmacológico , Sarcoma/metabolismo , Proteínas WT1/genética
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