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1.
J Sci Med Sport ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-39097510

RESUMEN

OBJECTIVES: The aim is to assess performance characteristics in jumps and functionality in participants with patellar tendinopathy and compare changes with various tendinopathy treatments in the short and medium term. As a secondary objective, the study aims to verify the relationship between changes in knee functionality assessed by the VISA-P and jump capacity in the different treatment groups. DESIGN: A double-blinded randomized controlled trial. METHODS: Recruitment was conducted at sport clubs, with 48 participants with patellar tendinopathy included in the study. Participants were randomized into groups: dry needling (DN), percutaneous electrolysis (PNE), and sham needling as the control group (CG), all combined with eccentric exercise (EE). Functionality and performance during jumps, including squat jump (SJ) and counter movement jump (CMJ), were assessed. RESULTS: Significant differences were found in functionality between the pre-test and post-test evaluations, as well as between the pre-test and follow-up evaluations, in all three groups (p < 0.001). The DN group experienced an improvement in eccentric power (p = 0.021). A moderate correlation was found between the pre-test and post-test changes in functionality and SJ maximum concentric force (r = 0.63, p < 0.01, CI: 0.1; 0.8), CMJ maximum concentric force (r = 0.52, p = 0.05, CI: -0.01; 0.8), and CMJ eccentric power in the DN group (r = 0.63, p = 0.01, CI: 0.1; 0.8). CONCLUSIONS: Eccentric exercise could be effective in improving functionality in patellar tendinopathy and DN could improve eccentric power in jumps performance. Moreover, the DN group experienced an increase in functionality that correlated with the improvements found in jump performance in eccentric power and concentric strength.

2.
Food Chem Toxicol ; 188: 114627, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561037

RESUMEN

Testes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular metabolome and the possible influence in the gut-gonad crosstalk. For this, BALB/c mice were given flumequine and diclofenac orally in food and potentially toxic trace elements (Cd, Hg, As) in drinking water. A mice group was supplemented with selenium, a well-known antagonist against many pollutants. Our results revealed that the steroid 5-alpha-androstan-17-beta-ol propionate, suggested as a parameter of androgenicity independent of testosterone levels, proline that improves reproductive indicators in male rabbits affected by environmental stress) among others metabolites are only present after CC exposure with rodent and selenium supplemented diet. Selenium also antagonized the up-or down-regulation of anandamide (20:l, n-9) (p < 0.001 and FC 0.54 of CC vs C but p > 0,05 and FC 0.74 of CC-Se vs C), that regulates gonadotropin-releasing hormones in mammals, 2,3-dinor-11b-PGF2a (p < 0.001 and FC 0.12 of CC vs C but p > 0,05 and FC 0.34 of CC-Se vs C), which has been related with reproductive hormones, besides others testicular metabolites altered by the exposure to the CC and reversed the levels to control. Moreover, numerous significant associations between gut microbes and testicular metabolites indicated a possible impact of pollutants in the testes mediated by gut microbiota due to a gut-gonad crosstalk.


Asunto(s)
Metabolómica , Ratones Endogámicos BALB C , Testículo , Animales , Masculino , Ratones , Testículo/efectos de los fármacos , Testículo/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Diclofenaco/toxicidad
3.
Rehabilitación (Madr., Ed. impr.) ; 57(4): [100810], Oct-Dic, 2023. ilus
Artículo en Español | IBECS | ID: ibc-228354

RESUMEN

Se presenta el caso de un varón de 68años con un cuadro progresivo de hipoestesia braquial y crural con ataxia de la marcha, sugiriendo una mielopatía subaguda de cordones posteriores, demostrada en RM. Tras analítica sanguínea se diagnostica de déficit de cobre tras intoxicación por zinc, secundario al uso de un pegamento para dentaduras postizas que contenía zinc. Se inició tratamiento con cobre, retirándose el pegamento dental. Se inició tratamiento rehabilitador con fisioterapia, hidroterapia y terapia ocupacional. Se consiguió una mejoría funcional, pasando de una lesión medular ASIAD nivel C4 a otra ASIAD nivel C7. Deberían estudiarse los niveles de cobre en todas aquellas mielopatías no compresivas, de aparición subaguda, si existe una clara afectación de los cordones posteriores. El déficit de cobre en análisis establecería el diagnóstico. El tratamiento rehabilitador, el aporte de cobre suplementario y la retirada del zinc es fundamental para la prevención de daño neurológico irreversible.(AU)


We present the case of a 68-year-old man with progressive brachial and crural hypoaesthesia with gait ataxia suggesting subacute myelopathy of the posterior cords, demonstrated by MRI. After blood tests, a diagnosis of copper deficiency was made following zinc intoxication, secondary to the use of denture glue containing zinc. Treatment was started with copper and the dental glue was removed. Rehabilitation treatment was started with physiotherapy, hydrotherapy and occupational therapy. Functional improvement was achieved, going from an ASIAD level C4 to an ASIAD level C7 spinal cord injury. Copper levels should be studied in all non-compressive myelopathies of subacute onset if there is clear involvement of the posterior cords. Copper deficiency in analysis would establish the diagnosis. Rehabilitative treatment, supplementary copper supplementation and zinc withdrawal are essential to prevent irreversible neurological damage.(AU)


Asunto(s)
Humanos , Masculino , Anciano , Resultado del Tratamiento , Enfermedades de la Médula Espinal/diagnóstico , Cobre , Zinc , Traumatismos de la Médula Espinal , Pacientes Internos , Examen Físico , Rehabilitación , Enfermedades de la Médula Espinal/complicaciones
4.
Rehabilitacion (Madr) ; 57(4): 100810, 2023.
Artículo en Español | MEDLINE | ID: mdl-37399638

RESUMEN

We present the case of a 68-year-old man with progressive brachial and crural hypoaesthesia with gait ataxia suggesting subacute myelopathy of the posterior cords, demonstrated by MRI. After blood tests, a diagnosis of copper deficiency was made following zinc intoxication, secondary to the use of denture glue containing zinc. Treatment was started with copper and the dental glue was removed. Rehabilitation treatment was started with physiotherapy, hydrotherapy and occupational therapy. Functional improvement was achieved, going from an ASIAD level C4 to an ASIAD level C7 spinal cord injury. Copper levels should be studied in all non-compressive myelopathies of subacute onset if there is clear involvement of the posterior cords. Copper deficiency in analysis would establish the diagnosis. Rehabilitative treatment, supplementary copper supplementation and zinc withdrawal are essential to prevent irreversible neurological damage.


Asunto(s)
Enfermedades de la Médula Espinal , Traumatismos de la Médula Espinal , Masculino , Humanos , Anciano , Cobre , Zinc , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/complicaciones
5.
J Hazard Mater ; 438: 129444, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35999733

RESUMEN

Biological systems are exposed to a complex environment in which pollutants can interact through synergistic or antagonistic mechanisms, but limited information is available on the combined effects. To this end, conventional and antibiotic-treated (Abx) mice models were fed regular rodent or selenium (Se) supplemented diets and exposed to a "chemical cocktail" (CC) including metals and pharmaceuticals. Metallomics, metabolomics, and metataxomics were combined to delve into the impact on gut microbiota, plasma selenoproteome, metabolome, and arsenic metabolization. At the molecular level, Se decreased the concentration of the antioxidant glutathione peroxidase in plasma and increased the arsenic methylation rate, possibly favoring its excretion, but not in the Abx and also plasma metabolomes of Abx, and Abx-Se were not differentiated. Moreover, numerous associations were obtained between plasma selenoproteins and gut microbes. Se-supplementation partially antagonizes the gut microbiota alteration caused by Abx, and slightly by CC, but strongly altered profiles were observed in CC-Abx-Se, suggesting synergistic deleterious effects between pollutants, Abx and Se. Moreover, although CC and Abx changed gut microbiota, several common taxa were enriched in CC-Abx and control mice, indicating possible synergistic effects. Our results suggest a potential beneficial impact of supplementation, but mediated by gut microbes being reversed in their absence.


Asunto(s)
Arsénico , Contaminantes Ambientales , Microbioma Gastrointestinal , Selenio , Animales , Arsénico/toxicidad , Suplementos Dietéticos , Ratones , Preparaciones Farmacéuticas , Selenio/farmacología
6.
Clin Nutr ; 41(8): 1680-1688, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35777107

RESUMEN

BACKGROUND AND AIMS: We aimed to describe and characterize the gut microbiota composition and diversity in children with obesity according to their metabolic health status. METHODS: Anthropometry, Triglycerides, HDL cholesterol, HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated (and z-score calculated) and faecal samples were collected from 191 children with obesity aged from 8 to 14. All children were classified depending on their cardiometabolic status in either a "metabolically healthy" (MHO; n = 106) or "metabolically unhealthy" (MUO; n = 85) group. Differences in gut microbiota taxonomies and diversity between groups (MUO vs MHO) were analysed. Alpha diversity index was calculated as Chao1 and Simpson's index, and ß-diversity was calculated as Adonis Bray-Curtis index. Spearman's correlations and logistic regressions were performed to study the association between cardiometabolic health and the microbiota. RESULTS: Children in the MUO presented significantly lower alpha diversity and richness than those in the MHO group (Chao1 index p = 0.021, Simpson's index p = 0.045, respectively), whereas microbiota ß-diversity did not differ by the cardiometabolic health status (Adonis Bray-Curtis, R2 = 0.006; p = 0.155). The MUO group was characterized by lower relative abundances of the genera Christensenellaceae R7 group (MHO:1.42% [0.21-2.94]; MUO:0.47% [0.02-1.60], p < 0.004), and Akkermansia (MHO:0.26% [0.01-2.19]; MUO:0.01% [0.00-0.36], p < 0.001) and higher relative abundances of Bacteroides (MHO:10.6% [4.64-18.5]; MUO:17.0% [7.18-27.4], p = 0.012) genus. After the adjustment by sex, age, and BMI, higher Akkermansia (OR: 0.86, CI: 0.75-0.97; p = 0.033), Christensenellaceae R7 group (OR: 0.86, 95% CI: 075-0.98; p = 0.031) and Chao1 index (OR: 0.86, CI: 0.96-1.00; p = 0.023) represented a lower risk of the presence of one or more altered cardiovascular risk factors. CONCLUSION: Lower proportions of Christensenellaceae and Akkermansia and lower diversity and richness seem to be indicators of a metabolic unhealthy status in children with obesity.


Asunto(s)
Enfermedades Cardiovasculares , Microbioma Gastrointestinal , Síndrome Metabólico , Antropometría , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Niño , Humanos , Obesidad , Factores de Riesgo
7.
J Hazard Mater ; 438: 129443, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35816792

RESUMEN

Several environmental pollutants have been shown to damage brain and affect gut microbiota. Limited evidence is available about the impact of "chemical cocktails" (CC) of xenobiotics on brain metabolome and their possible influence in the gut-brain crosstalk. To this end, BALB/c mice were exposed to heavy metals (As, Hg, Cd) and pharmaceuticals (diclofenac and flumequine) under regular rodent diet or supplemented with selenium (Se). Selenium, an antioxidant well-known for its antagonism against the neurotoxicity of several pollutants, modulated several brain metabolic impairments caused by CC (e.g., brain levels of the excitatory amino acid N-acetyl aspartic acid) by influencing mainly the metabolisms of purine, glycosylate and dicarboxylate, glutamate, glycerophospholipid, alanine and aspartate. Numerous associations were obtained between brain metabolites and gut microbes and they changed after Se-supplementation (e.g., Lactobacillus was positively associated with a brain ceramide, phosphoserine, phosphocholine, vitamin D3 derivative, fatty acids, malic acid, amino acids, and urea after the exposure, but not after Se-supplementation). Our results showed numerous evidences about the impact of CC on brain metabolome, the potential role of Se as an antagonist and their impact on the gut-brain axis. Further research is needed to understand the complex mechanism of action implied on CC-brain-microbiota interactions.


Asunto(s)
Contaminantes Ambientales , Selenio , Animales , Encéfalo , Eje Cerebro-Intestino , Suplementos Dietéticos , Metaboloma , Metabolómica/métodos , Ratones , Selenio/toxicidad , Xenobióticos
8.
Eur J Nutr ; 60(3): 1429-1442, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32728880

RESUMEN

BACKGROUND: Diet has an important role in host-microbiome interplay, which may result in intestinal permeability changes and physiopathological effects at a systemic level. Despite the importance of maternal microbiota as the main contributor to the initial microbial seeding, little is known about the effects of maternal diet during pregnancy on maternal-neonatal microbiota. OBJECTIVES: This study aimed at ascertaining the possible associations between maternal dietary intake during pregnancy and neonatal microbiota at birth and to evaluate the relationship with maternal intestinal markers. METHODS: In a nested cross-sectional study in the longitudinal MAMI cohort, maternal-neonatal microbiota profiling at birth (n = 73) was assessed by 16S rRNA gene sequencing. Maternal intestinal markers as zonulin, intestinal alkaline phosphatase (IAP) activity and faecal calprotectin were measured in faeces. Furthermore, maternal-neonatal clinical and anthropometric data, as well as maternal nutrient intake during pregnancy obtained by FFQ questionnaires, were collected. RESULTS: Maternal diet is associated with both maternal and neonatal microbiota at the time of birth, in a delivery mode-dependent manner. The existing link between maternal diet, intestinal makers and neonatal gut microbiota would be mainly influenced by the intake of saturated (SFA) and monounsaturated fatty acids (MUFA). Members of Firmicutes in the neonatal microbiota were positively associated with maternal fat intake, especially SFA and MUFA, and negatively correlated to fibre, proteins from vegetable sources and vitamins. CONCLUSIONS: Maternal diet during pregnancy, mainly fat intake (SFA and MUFA), was related to intestinal markers, thus likely shifting the microbial transmission to the neonate and priming the neonatal microbial profile with potential health outcomes. CLINICAL TRIAL REGISTRY: NCT03552939.


Asunto(s)
Microbioma Gastrointestinal , Estudios Transversales , Dieta , Femenino , Humanos , Recién Nacido , Intestinos , Embarazo , ARN Ribosómico 16S/genética
9.
Microbiome ; 8(1): 167, 2020 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-33228771

RESUMEN

BACKGROUND: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. METHODS: Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. RESULTS: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. CONCLUSIONS: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. TRIAL REGISTRATION: NCT03552939 . Video Abstract.


Asunto(s)
Entorno del Parto , Desarrollo Infantil , Microbioma Gastrointestinal/fisiología , Recién Nacido/crecimiento & desarrollo , Intestinos/microbiología , Intestinos/fisiología , Cesárea , Femenino , Microbioma Gastrointestinal/genética , Parto Domiciliario , Hospitalización , Humanos , Lactante , Masculino , Embarazo , ARN Ribosómico 16S/genética
10.
Artículo en Inglés | MEDLINE | ID: mdl-32963575

RESUMEN

The aim was to determine the effectiveness of minimally invasive techniques (MIT) in patients with patellar tendinopathy. Database searches were performed for randomized controlled trials (RCTs) in electronic databases (WOS, Cochrane Central, SportDiscus, and Medline via PubMed and PEDro). The inclusion criteria used were published in English or Spanish and involving adults with patellar tendinopathy (pain on the inferior pole of the patella for a minimum of 3 months), with at least one group receiving MIT. The quality of the relevant RCTs was evaluated using the PEDro scale. The primary outcome was functionality using the VISA-p questionnaire. Secondary outcome was focused on pain. A total of 1164 studies were screened for possible inclusion in our systematic review. Finally, 10 RCTs were included with a total of 326 individuals. Five RCTs were included in the meta-analysis. The quality assessment revealed that all the studies included were considered to possess high methodological quality. All studies analyzing MIT such as platelet-rich plasma (PRP), dry needling, or skin-derived tenocyte-like cells, when combined with exercise, proved to be effective for patellar tendinopathy. Moreover, the PRP technique with doses greater than 4 mL together and combined with an exercise program lasting over 6 weeks obtained better results in functionality and pain than other treatments in the short term. However, in the long term, dry needling and skin-derived tenocyte-like cells are more effective than PRP. Although the infiltration of drugs was effective at posttreatment, these improvements were not maintained over time and may have secondary effects. Although there are no RCTs analyzing the effectiveness of MIT like percutaneous needle electrolysis, there has been an increasing number of publications achieving excellent results in the last years. However, it is necessary to develop RCTs analyzing not only the effect but also comparing the effectiveness between different MIT such as dry needling and percutaneous needle electrolysis.

11.
J Comp Pathol ; 167: 32-40, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30898295

RESUMEN

Chicken anaemia virus (CAV) causes chicken infectious anaemia, a severe disease characterized by anaemia and immunosuppression and leading to serious economic losses in the poultry industry worldwide. Although CAV infection has been investigated under experimental conditions, information regarding natural infection is scarce. This report describes an outbreak of CAV infection in 18-day-old broiler chickens and investigates virus tropism in affected birds. Thymic atrophy, pale bone marrow, swelling of the legs and foot ulcers (gangrenous dermatitis) were the most common gross lesions. Severe lymphoid cell depletion in the thymic cortex and presence of intranuclear acidophilic inclusion bodies, depletion of haemopoietic cells in bone marrow and presence of lymphoid infiltrates in several organs were also observed. Immunohistochemical labelling demonstrated the CAV antigens VP1 and VP3 in several organs. The expression of both proteins was similar in the thymic cortex and in the bone marrow, the main target organs of CAV; however, VP3 expression was more abundant in the other organs. Labelling of serial sections showed that CD3+ T lymphocytes might be responsible for the dissemination of the virus from the thymus and bone marrow to other organs and that virus-induced apoptosis, mediated through caspase-3, occurred mainly in the thymus and bone marrow.


Asunto(s)
Infecciones por Circoviridae/veterinaria , Enfermedades de las Aves de Corral/virología , Tropismo Viral , Animales , Virus de la Anemia del Pollo , Pollos
12.
J Bodyw Mov Ther ; 23(1): 122-137, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30691739

RESUMEN

BACKGROUND: Minimally invasive non-surgical techniques have been widely used worldwide to treat musculoskeletal injuries. Of these techniques, injectable pharmaceutical agents are the most commonly employed treatments, with corticosteroids being the most widely used drugs. The aim of this article is to review current scientific evidence as well as the effectiveness of minimally invasive non-surgical techniques, either alone or combined, for the treatment of plantar fasciitis. METHODS: This systematic review was conducted from April 2016 until March 2017, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and was registered with PROSPERO. Randomized controlled trials (RCTs) of adult patients diagnosed with plantar fasciitis were included as well as intervention studies, with a minimal sample size of 20 subjects per study (10 per group). Assessment of study eligibility was developed by three reviewers independently in an unblinded standardized manner. The physiotherapy evidence database (PEDro) scale was used to analyse the methodological quality of studies. RESULTS: Twenty-nine full-text articles on minimally invasive techniques were reviewed. These articles focused on corticosteroid injections, platelet-rich plasma, Botox, dextrose injections, as well as comparative studies with dry needling vs sham needling. CONCLUSION: The treatment of plantar fasciitis has dramatically improved in the past decade with minimally invasive techniques becoming increasingly available. Research findings have shown that the long term effects of minimally invasive (non-surgical) treatments such as shock wave therapy, botulinum toxin type-A injections, platelet-rich plasma injections and intratissue percutaneous electrolysis dry needling show similar and sometimes better results when compared to only corticosteroid injections. The latter have been the mainstay of treatment for many years despite their associated side effects both locally and systemically. To date, there is no definitive treatment guideline for plantar fasciitis, however the findings of this literature review may help inform practitioners and clinicians who use invasive methods for the treatment of plantar fasciitis regarding the levels of evidence for the different treatment modalities available.


Asunto(s)
Fascitis Plantar/terapia , Manejo del Dolor/métodos , Terapia por Acupuntura/métodos , Corticoesteroides/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Glucosa/uso terapéutico , Humanos , Inyecciones Intraarticulares , Dimensión del Dolor , Modalidades de Fisioterapia , Plasma Rico en Plaquetas , Polidesoxirribonucleótidos/uso terapéutico , Tratamiento de Tejidos Blandos/métodos
13.
Transplant Proc ; 50(2): 601-604, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29579864

RESUMEN

INTRODUCTION: Donation after circulatory death (DCD) has increased in the last decade, although a slight increase in surgical complications has been reported in liver transplantation (LT). Therefore, DCD is not recommended with donors aged 60 years or more because it entails an added risk. However, donation after brain death (DBD)-LT with donors aged 70 years or more shows acceptable results. OBJECTIVE: The objective was to analyze the characteristics and complications of DCD-LT with donors aged 70 years or more (DCD-70). MATERIALS AND METHODS: We included 14 DCD-70-LT and compared them with a control group of 28 DBD-LT aged 70 years or more. STATISTICAL ANALYSIS: A descriptive analysis, Mann-Whitney U test, and Pearson chi-square or Fisher test were performed when appropriate. RESULTS: Significant differences were found in aminotransferase peak at 24 hours, with an increase in the DCD-70 group (aspartate aminotransferease [AST] 1038 vs 507, P = .013; alanine aminotransferase [ALT] 750 vs 399, P = .014). The cold ischemia time was lower in DCD-70 although without significant differences (4.8 vs 6.7 hours). Biliary complications (28.6% vs 31.7%) and vascular complications (7.1% vs 7.1%) were similar. A single transplant with DCD-70 required a retransplantation due to arterial thrombosis. Mortality was the same in both cases (14.3%). CONCLUSION: LT results with DCD-70 are similar to those of DBD-70, so the age criteria could also be extended in this type of donation.


Asunto(s)
Muerte Encefálica , Trasplante de Hígado/métodos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Choque , Factores de Tiempo
14.
Fam Cancer ; 16(4): 567-575, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28573494

RESUMEN

Li-Fraumeni syndrome (LFS) is an autosomal dominant, inherited tumor predisposition syndrome associated with heterozygous germline mutations in the TP53 gene. The molecular diagnosis of LFS is important to develop strategies for early detection and access to the genetic counseling. Our study evaluated germline TP53 mutations in Spanish families with a history suggestive of LFS. Germline TP53 alterations in 22 families with a history suggestive of LFS were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Loss of heterozygosity analysis and immunohistochemistry of the protein in the tumor were performed in order to evaluate the pathogenicity of a novel alteration detected. A total of seven TP53 mutations were detected, six point mutations (4 missense and 2 nonsense) and a novel inframe deletion. 93% of mutation carriers developed at least one malignancy (mainly breast cancer and sarcomas), with a mean age at diagnosis of the first tumor of 30.2 years. Two missense mutations acted as dominant-negative. The novel inframe mutation c.437_445del was located in the DNA-binding domain. This mutation segregated with cancer in the family, and both high expression of the protein and loss of the wild-type TP53 allele were detected in the tumor of the carrier. We have found a novel inframe deletion in TP53 that likely results in the loss of p53 function and acts in a non-dominant negative way, although further studies are necessary to clarify this issue. The identification of novel TP53 alterations is crucial for a personalized cancer-risk management of the Li-Fraumeni syndrome.


Asunto(s)
Mutación de Línea Germinal , Síndrome de Li-Fraumeni/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Femenino , Humanos , Pérdida de Heterocigocidad , Masculino , Linaje , España , Proteína p53 Supresora de Tumor/metabolismo
15.
Clin Transl Oncol ; 19(6): 761-768, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28054320

RESUMEN

BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Terapia Recuperativa/métodos , España , Resultado del Tratamiento
16.
Vet Pathol ; 54(1): 82-93, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27315822

RESUMEN

Animals infected with Mycobacterium avium subspecies paratuberculosis show a variety of granulomatous lesions that range from focal forms, seen in the subclinical stages, to diffuse lesions associated with clinical signs. The aim of this study was to phenotypically characterize the macrophages present in the different lesion types using immunohistochemical methods. Lesions from a total of 23 animals with bovine paratuberculosis, natural and experimental, were examined by immunohistochemistry. Antibodies against inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), CD163, interleukin 10 (IL-10), transforming growth factor ß (TGF-ß), major histocompatibility complex (MHC) class II, natural resistance-associated macrophage protein 1 (Nramp-1), calprotectin, Ki-67, CD68, lysozyme, and ionized calcium-binding adaptor molecule 1 (Iba-1) molecules were employed. Samples were scored semiquantitatively using a complete histological score (H-score), reflecting the staining intensity and the percentage of immunolabeled macrophages. Differences in the H-score were seen depending on the lesion type. In focal lesions, with none or few acid-fast bacilli (AFB), macrophages were polarized toward M1 phenotype, with high H-scores for iNOS and TNF-α. Diffuse multibacillary lesions showed M2 differentiation, with high expression of CD163, IL-10, and TGF-ß as well as Nramp-1 and MHC class II antigens. Macrophages in diffuse paucibacillary forms showed high H-scores for iNOS but low ones for TNF-α. Diffuse lesions, either multibacillary or paucibacillary, showed high calprotectin and low Ki-67 expression, suggesting a progressive character, while focal forms, with low H-scores for these antigens, would be consistent with latency. Lysozyme and CD68 expression were related to the amount of AFB. H-score for Iba-1 antibody was similar among all types. The findings of this study provide insights into the polarization status of macrophages and lesion development in bovine paratuberculosis.


Asunto(s)
Enfermedades de los Bovinos/patología , Intestinos/patología , Macrófagos/patología , Paratuberculosis/patología , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Femenino , Granuloma/patología , Granuloma/veterinaria , Interleucina-10/metabolismo , Intestinos/citología , Antígeno Ki-67/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
18.
Nano Lett ; 14(5): 2807-14, 2014 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-24745828

RESUMEN

Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of considerable technological importance but remains a challenge due to the amphoteric behavior of the dopant atoms. Here we show that placing a narrow GaAs quantum well in the AlAs shell effectively getters residual carbon acceptors leading to an unintentional p-type doping. Magneto-optical studies of such a GaAs/AlAs core-multishell NW reveal quantum confined emission. Theoretical calculations of NW electronic structure confirm quantum confinement of carriers at the core/shell interface due to the presence of ionized carbon acceptors in the 1 nm GaAs layer in the shell. Microphotoluminescence in high magnetic field shows a clear signature of avoided crossings of the n = 0 Landau level emission line with the n = 2 Landau level TO phonon replica. The coupling is caused by the resonant hole-phonon interaction, which points to a large two-dimensional hole density in the structure.

20.
Semergen ; 39(6): 304-8, 2013 Sep.
Artículo en Español | MEDLINE | ID: mdl-24034758

RESUMEN

OBJECTIVE: To describe the prescribing of topical non-steroidal anti-inflammatory drugs (NSAIDs) in an urban health center (Zaragoza, Spain). PATIENTS AND METHODS: A cross-sectional descriptive study was conducted on subjects who belonged to an urban center and were studied during the year 2010. The sample size with a confidence level of 95%, was calculated, a total of 843 prescriptions were analyzed. The sample was single random, and 150 cases were selected. The prevalence and confidence intervals were calculated. The statistical package STATA 9.1 was used for the calculations. RESULTS: The most used drug was diclofenac, in 27.33% (95% CI: 20.65-34.88). NSAIDs were most used in females. In 18% of the cases the area of application was the knee, followed by the 15% in the lower back area (95% CI: 10,22-21,78). There were no adverse reactions. CONCLUSIONS: Frequent use is made of topical NSAIDs in a basic health area. Current recommendations support the use in the knee and in the hand, but not in the back, where its use is common. The use of topical NSAIDs decreases side effects and drug interactions, therefore their use is recommended in patients on multiple drug therapy and in the elderly.


Asunto(s)
Antiinflamatorios no Esteroideos , Prescripciones de Medicamentos/estadística & datos numéricos , Administración Tópica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/administración & dosificación , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , España , Salud Urbana , Adulto Joven
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