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BACKGROUND: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. MATERIAL AND METHODS: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. RESULTS: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. CONCLUSIONS: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Metástasis Linfática , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/patología , Invasividad Neoplásica/patología , Pronóstico , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: The importance of Gram-positive microorganisms and atypical bacteria in chronic bacterial prostatitis (CBP) has recently been described. For this reason, this study analyzes the etiology of CBP, as well as the evolution of antibiotic resistance through a systematic review. METHODS: A systematic review of studies obtained through the MEDLINE (PubMed) database, related to the etiology and antibiotic resistance profile of CBP, published up July 1, 2021. RESULTS: The most frequent isolated microorganisms that we have found in publications are Enterococcus faecalis (46.90%), Staphylococcus spp. (22.30%), Escherichia coli (15.09%) and atypical bacteria (6.04%). CONCLUSIONS: CBP is undergoing and unprecedented change of paradigm. Gram-positive bacteria and atypical bacteria are the main pathogens involved in the aetiology of this entity. This forces us to rethink the therapeutic strategy used, since it is necessary to use antibiotics that assume the etiological change and the profile of antibiotic resistance described.
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Infecciones Bacterianas , Prostatitis , Masculino , Humanos , Prostatitis/tratamiento farmacológico , Prostatitis/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Bacterias , Antibacterianos/uso terapéutico , Bacterias Grampositivas , Escherichia coli , Enfermedad CrónicaRESUMEN
Mini-puberty refers to the transient activation of the hypothalamic-pituitary-gonadal axis during the first months of life. This activation in preterm infants could be more exaggerated and prolonged. Ob jective: To present a case of exaggerated mini-puberty in an extremely preterm infant, with recurrent genital bleeding. Clinical Case: A 25-week preterm newborn presented at 5 months old with breast buds, areolar pigmentation, and estrogenic effects on the vaginal mucosa, with recurrent genital blee ding in three consecutive months. Her laboratory evaluation showed elevated values of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2). An exaggerated mini-puber ty due to extreme prematurity was suspected, therefore a conservative approach was taken. During follow-up, the patient showed partial regression of breast buds and cessation of genital bleeding, and decreasing levels of gonadotropin and estradiol. Conclusion: Mini-puberty in preterm newborns can present exaggeratedly, simulating precocious puberty and even presenting, exceptionally, recurrent genital bleeding. Considering the increasing survival of extremely premature infants, it is important to know the spectrum of clinical and laboratory manifestations of this phenomenon, in order to carry out adequate management.
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Estradiol , Hormona Luteinizante , Femenino , Genitales , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Pezones , RecurrenciaRESUMEN
AIM: Despite its limitation, bag collection is still widely used for a preliminary urine screening test in non-toilet-trained children suspected of febrile urinary tract infection. A previous study conducted by our group raised the hypothesis that the absence of direct contact between urine and the perinea during urine collection could limit urine contamination by perineal flora. The aim of this study was to evaluate the impact of the patient's position during urine collection (upright standing position versus free position) on the rate of contaminated urine samples in non-toilet-trained children with suspected febrile urinary tract infection. METHODS: This prospective, randomized, controlled study took place in seven pediatric emergency departments. Two groups were compared: the intervention group (infants held in an upright standing position during urination) and the control group (free position during urination). RESULTS: Among the 800 pediatric patients randomized to the study, 124 had a urine culture, 60 in the intervention group and 64 in the control group. Among the 124 urine cultures, 12 (9.7%) were contaminated: eight (13.3%) in the intervention group and four (6.3%) in the control group (p = 0.1824). CONCLUSION: The results show that the patient's position does not have a significant impact on the quality of urine samples collected by bag.
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Infecciones Urinarias , Toma de Muestras de Orina , Niño , Humanos , Lactante , Estudios Prospectivos , Urinálisis , Infecciones Urinarias/diagnóstico , Micción , Toma de Muestras de Orina/métodosRESUMEN
The use of anionic salts to prevent milk fever in dairy cattle has been an effective nutritional strategy; however, the degree of acidification that determines the most acceptable productive responses and well-being of the cow is still a controversial topic. The objective of this study was to assess urine pH in prepartum Holstein cows fed anionic diets and determine its association with plasma total Ca, Mg, P, ß-hydroxyl-butyrate (BHB) concentrations at parturition and the occurrence of peripartum disorders. This investigation consisted of 2 studies. Study 1 was conducted on a grazing dairy. Between February and May 2019, 60 prepartum multiparous cows were tested for urine pH and plasma metabolite concentration at parturition. Total Ca, P, Mg and BHB at day 1 in milk (DIM) were assessed and statistically analyzed by ANOVA (models for polynomial regression). Study 2 was conducted on a drylot dairy farm. Between July 2018 and January 2019, 203 cows were evaluated for urine pH and followed-up for 30 DIM to obtain the incidence of dystocia, stillbirths, milk fever, retained fetal membranes, metritis, clinical mastitis and ketosis. Cows were categorized based on their last urine pH as group 1: pHâ¯>â¯7.0 (nâ¯=â¯135); group 2: pH between 6.0 and 7.0 (nâ¯=â¯46) and group 3: pHâ¯<â¯6.0 (nâ¯=â¯22). A logistic regression model for each health event was conducted considering urine pH group as the main effect. Urine sample was collected at 2.71⯱â¯2.84â¯days before parturition. In study 1, there was a quadratic effect of urine pH on total Ca. Total Ca concentration was higher between urine pHâ¯6.0 and 7.0, while decreasing below pHâ¯6.0 and above pHâ¯7.0. There was a trend (Pâ¯=â¯0.11) for a quadratic effect of urine pH on the concentration of plasma BHB at parturition. ß-Hydroxyl-butyrate was lower approximately between urine pHâ¯6.5 and 7.5. In study 2, the odds for a stillborn in cows with urine pHâ¯<â¯6.0 was 2.39 (95% CIâ¯=â¯1.06-5.40) times the odds for a stillborn in cows with urine pHâ¯≥â¯7.0. There was no association between urine pH and the other diseases. In conclusion, cows with prepartum urine pHâ¯<â¯6.0 and >7.0 had lower concentration of plasma total Ca and tended to have a higher concentration of BHB. Cows with urine pHâ¯<â¯6.0 had a higher incidence of stillbirths than cows with urine pHâ¯>â¯7.0.
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Enfermedades de los Bovinos , Lactancia , Animales , Calcio , Bovinos , Enfermedades de los Bovinos/epidemiología , Dieta , Femenino , Concentración de Iones de Hidrógeno , Leche , Plasma , Periodo Posparto , EmbarazoRESUMEN
Platelet rich plasma (PRP) is used to speed up tissue repair. Despite its widespread use, the therapeutic application of PRP generates controversies in clinical results due to the variability in methods of obtaining the different preparations and differences between the components of different types of PRP, so it's recommended to mention the type of platelet preparation used. In this article, we describe technical and biologics characteristics of our platelet product, and we compare them to different commercial preparations described in order to validate their clinical use. Our results determine that the preparation can be considered a platelet rich plasma with biological activity in vivo and in vitro, which supports its use as a valid therapeutic tool, alternative to products currently available in Regenerative Medicine. (AU)
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Humanos , Medicina Regenerativa/tendencias , Plasma Rico en Plaquetas , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.
Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.
RESUMEN
Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.
La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.
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Humanos , Niño , Adulto , Prestación Integrada de Atención de Salud , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Chile , Estado Nutricional , Fibrosis Quística/rehabilitación , Consenso , Recursos en SaludRESUMEN
OBJECTIVE: Male genital infections are a major problem due to their high frequency and morbidity and their role in cases of male infertility. We studied the presence, in males assisted in specialized care, of non-ulcerative genital tract infections-producing agents. METHODS: We studied descriptively and retrospective microbiological results of 3,066 samples of male patients, with diagnosis of genital tract infection episode, received between January 1, 2016 and December 31, 2017. Detection of microorganisms in the sample was performed using techniques of artificial culture and PCR (BD-MAX). RESULTS: Positive results were obtained in 451 samples (14.71%). By culture, the most frequent pathogens were Enterobacterales (18.40%), Enterococcus (13.75%), Haemophilus (8.65%), Neisseria gonorrhoeae (8.43%), Ureaplasma (5.10%), and Candida (3.77%). By polymerase chain reaction (PCR), the most frequent were N. gonorrhoeae (28.37%), Chlamydia trachomatis (26.95%), Ureaplasma urealyticum (17.73%), Mycoplasma hominis/Ureaplasma parvum (10.64%), and Mycoplasma genitalium (7.10%). The age was older in patients infected with Enterobacterales, Candida, or Enterococcus and younger in those infected with N. gonorrhoeae. CONCLUSIONS: N. gonorrhoeae and C. trachomatis are still more common in male genital infection pathogens, although other culturable microorganisms have an important role. These findings demonstrate the importance of systematically applying both conventional culture and PCR techniques for pathogen detection.
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Infecciones del Sistema Genital/epidemiología , Infecciones del Sistema Genital/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios Transversales , Humanos , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
Nine wild Iberian provenances of Castanea sativa Mill. grouped in two gene pools, North Iberian Peninsula and Mediterranean, were evaluated for several adaptive traits in two provenance-progeny trials with the aim of evaluating the role of natural selection in shaping adaptive variation and increasing our understanding of the genetic structure of this species, as well as reporting complete information on the genetic variation among and within the studied populations. An annual growth rhythm experiment was evaluated during the first 3 years after establishment for phenology, growth, stem form and survival, and a periodic drought-stress experiment was evaluated for dry weight, growth, survival and other related drought traits in both well-watered and drought-stress treatments. The high genetic variability reported in both trials is largely due to the genetic variation among populations. The significant differences reported between quantitative genetic and neutral marker differentiation indicated the local adaptation of these populations through directional selection, mainly for phenology, growth and biomass allocation. A clinal variation among populations was determined through correlations of phenology with latitude and xerothermic index of the provenances, showing that central and southern Mediterranean populations had earlier phenology than northern populations and that drought played a relevant role in this differentiation. The significant correlation between phenological traits and the ancestry values in the Mediterranean gene pool supported the different pattern of behavior between both gene pools and also indicated the existence of two ecotypes: xeric and mesophytic ecotypes, corresponding to Mediterranean and North Iberian gene pools, respectively. The results obtained in the drought-stress experiment confirmed that, in general terms, xeric populations showed a greater adaptability to drought, with more developed root systems and higher survival than northern populations. Moreover, the genetic variability observed within populations indicated the potential response capacity of Iberian C. sativa populations to undergo fast adaptive evolution.
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Fagaceae/genética , Variación Genética , Adaptación Fisiológica , Evolución Biológica , Biomasa , Sequías , Ecotipo , Fagaceae/crecimiento & desarrollo , Pool de Genes , Región Mediterránea , Hojas de la Planta/crecimiento & desarrollo , Selección Genética , EspañaRESUMEN
Autoimmunity appears to play a role in abdominal aortic aneurysm (AAA) pathology. Although the chemokine CCL20 has been involved in autoimmune diseases, its relationship with the pathogenesis of AAA is unclear. We investigated CCL20 expression in AAA and evaluated it as a potential biomarker for AAA. CCL20 was measured in plasma of AAA patients (n = 96), atherosclerotic disease (AD) patients (n = 28) and controls (n = 45). AAA presence was associated with higher plasma levels of CCL20 after adjustments for confounders in the linear regression analysis. Diagnostic performance of plasma CCL20 was assessed by ROC curve analysis, AUC 0.768 (CI:0.678-0.858; p<0.001). Classification and regression tree analysis classified patients into two CCL20 plasma level groups. The high-CCL20 group had a higher number of AAA than the low-CCL20 group (91% vs 54.3%, p< 0.001). mRNA of CCL20 and its receptor CCR6 were higher in AAA (n = 89) than in control aortas (n = 17, p<0.001). A positive correlation was found between both mRNA in controls (R = 0674; p = 0.003), but not in AAA. Immunohistochemistry showed that CCR6 and CCL20 colocalized in the media and endothelial cells. Infiltrating leukocytes immunostained for both proteins but only colocalized in some of them. Our data shows that CCL20 is increased in AAA and circulating CCL20 is a high sensitive biomarker of AAA.
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Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/diagnóstico , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Quimiocina CCL20/sangre , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , PronósticoRESUMEN
Objetivos: La prostatitis crónica bacteriana (PCB) es la enfermedad urológica más frecuente en menores de 50 años, cuya clínica de larga evolución puede estar relacionada con una inadecuada pauta terapéutica. El objetivo fue analizar la sensibilidad de los microorganismos aislados de pacientes con PCB y medir las concentraciones de antibiótico semanalmente en suero, semen y orina. Material y métodos: Para el estudio de la sensibilidad antibiótica, entre enero de 2013 y diciembre de 2014 se incluyeron 60 aislados clínicos procedentes de muestras de semen de pacientes confirmados microbiológicamente con PCB, y se llevó a cabo por microdilución en caldo. Para el estudio de las concentraciones de antibióticos, entre los meses de enero y mayo de 2014 se recogieron muestras de orina, sangre y semen, semanalmente, durante 4 semanas de tratamiento de 8 pacientes con cultivo positivo para PCB, y se midieron las concentraciones mediante cromatografía de líquidos de ultra alta eficacia acoplada a espectrometría de masas en tándem (UHPLC-MS/MS). Resultados: Fosfomicina y nitrofurantoína fueron los antibióticos con mayor actividad (95,2% en ambos casos). Las concentraciones medias de antibiótico en semen durante las 4 semanas estudiadas fueron las siguientes: 1,68 mg/l; 8,30 mg/l; 2,61 mg/l; 0,33 mg/l y 2,90 mg/l, respectivamente para los pacientes 1 a 5, que recibieron levofloxacino; 1,625 mg/l para el paciente 6, que recibió ciprofloxacino 2,67 mg/l para el paciente 7, que fue tratado con ampicilina, y 1,05 mg/l para el paciente 8, que recibió doxiciclina. Se obtuvieron mayores concentraciones en las muestras de orina que en suero y semen, siendo coparables estas 2 últimas. Conclusiones: Fosfomicina se postula como principal alternativa al tratamiento empírico de la PCB por su elevada actividad in vitro. La concentración de antibiótico en semen fue superior a la concentración mínima inhibitoria frente al agente etiológico, aunque no siempre se correlacionó la negativización microbiológica con la evolución clínica favorable
Objectives: Chronic bacterial prostatitis (CBP) is the most common urological disease in patients younger than 50 years, whose long-standing symptoms could be related to an inappropriate therapeutic regimen. The objective was to analyse the sensitivity of microorganisms isolated from patients with CBP and measure the weekly antibiotic concentrations in serum, semen and urine. Material and methods: For the antibiotic sensitivity study, 60 clinical isolates were included between January 2013 and December 2014 from semen samples from patients with microbiologically confirmed CBP. Broth microdilution was performed on the samples. For the antibiotic concentration study from January to May 2014, urine, blood and semen samples were collected weekly, over 4 weeks of treatment from 8 patients with positive cultures for CBP. The concentrations were measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Results: The antibiotics fosfomycin and nitrofurantoin had the highest activity (95.2% in both cases). The mean antibiotic concentrations in semen during the 4 weeks studied were as follows: 1.68 mg/L, 8.30 mg/L, 2.61 mg/L, 0.33 mg/L and 2.90 mg/L, respectively, for patients 1 to 5, who were treated with levofloxacin; 1.625 mg/L for patient 6, who was treated with ciprofloxacin; 2.67 mg/L for patient 7, who was treated with ampicillin; and 1.05 mg/L for patient 8, who was treated with doxycycline. Higher concentrations were obtained in the urine samples than in serum and semen, the latter 2 of which were comparable. Conclusions: Fosfomycin is proposed as the primary alternative to the empiric treatment of CBP due to its high in vitro activity. The antibiotic concentration in semen was higher than the minimal inhibitory concentration against the aetiological agent, although microbiological negativisation was not always correlated with a favourable clinical outcome
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Humanos , Antibacterianos/farmacocinética , Prostatitis/microbiología , Infecciones del Sistema Genital/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Antibacterianos/aislamiento & purificación , Fosfomicina/farmacocinética , Nitrofurantoína/farmacocinética , Análisis de SemenRESUMEN
OBJECTIVES: Chronic bacterial prostatitis (CBP) is the most common urological disease in patients younger than 50 years, whose long-standing symptoms could be related to an inappropriate therapeutic regimen. The objective was to analyse the sensitivity of microorganisms isolated from patients with CBP and measure the weekly antibiotic concentrations in serum, semen and urine. MATERIAL AND METHODS: For the antibiotic sensitivity study, 60 clinical isolates were included between January 2013 and December 2014 from semen samples from patients with microbiologically confirmed CBP. Broth microdilution was performed on the samples. For the antibiotic concentration study from January to May 2014, urine, blood and semen samples were collected weekly, over 4 weeks of treatment from 8 patients with positive cultures for CBP. The concentrations were measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). RESULTS: The antibiotics fosfomycin and nitrofurantoin had the highest activity (95.2% in both cases). The mean antibiotic concentrations in semen during the 4 weeks studied were as follows: 1.68mg/L, 8.30mg/L, 2.61mg/L, 0.33mg/L and 2.90mg/L, respectively, for patients 1 to 5, who were treated with levofloxacin; 1.625mg/L for patient 6, who was treated with ciprofloxacin; 2.67mg/L for patient 7, who was treated with ampicillin; and 1.05mg/L for patient 8, who was treated with doxycycline. Higher concentrations were obtained in the urine samples than in serum and semen, the latter 2 of which were comparable. CONCLUSIONS: Fosfomycin is proposed as the primary alternative to the empiric treatment of CBP due to its high in vitro activity. The antibiotic concentration in semen was higher than the minimal inhibitory concentration against the aetiological agent, although microbiological negativisation was not always correlated with a favourable clinical outcome.
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Antibacterianos/metabolismo , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Prostatitis/metabolismo , Prostatitis/microbiología , Antibacterianos/análisis , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Infecciones Bacterianas/tratamiento farmacológico , Enfermedad Crónica , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Prostatitis/tratamiento farmacológico , Semen/metabolismo , Factores de TiempoRESUMEN
Stroke modifies the composition of cell membranes by eliciting the breakdown of membrane phospholipids whose products, such as arachidonic acid (AA), are released in the cytosol. The action of enzymes such as cyclooxygenases on AA leads to inflammatory stimuli and increases the cell oxidative stress. We report here the neuroprotective effect of 2-hydroxyarachidonic acid (2OAA), a cyclooxygenase inhibitor derived from AA, as a promising neuroprotective therapy against stroke. The effect of a single dose of 2OAA, administered intragastrically 1h after the ischaemic insult, in a rat model of transient middle cerebral artery occlusion (tMCAO) was tested after 24h of reperfusion. Infarct volume was measured by TTC method to evaluate the neuroprotective effect. Levels of phospholipids and neutral lipids were measured by thin-layer chromatography. The expression of cPLA2 and sPLA2 phospholipases responsible for the cleavage of membrane phospholipids, as well as the expression of antioxidant enzymes, was measured by qPCR. Lipid peroxidation was measured as the concentration of malondialdehyde and 4-hydroxynonenal. The treatment with 2OAA reduced the infarct volume and prevented ischaemia-induced increases in transcription levels of free fatty acid (FFAs), as well as in both phospholipases A2 (cPLA2 and sPLA2). The lipid peroxidation and the transcription levels of antioxidant enzymes induced by ischaemia were also decreased by this treatment. We conclude that 2OAA treatment results in a strong neuroprotective effect that seems to rely on a decrease in PLA2 transcriptional activity. This would reduce their action on the membrane phospholipids reducing reactive oxygen and nitrogen species generated by FFAs. Based on the transcriptional activity of the antioxidant enzymes, we conclude that the treatment prevents oxidative stress rather than promoting the antioxidant response. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
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Ácidos Araquidónicos/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Animales , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Peroxidación de Lípido , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Fosfolipasas A2/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Transit data analysis and artificial neural networks (ANNs) have proven to be a useful tool for characterizing and modelling non-linear hydrological processes. In this paper, these methods have been used to characterize and to predict the discharge of Lor River (North Western Spain), 1, 2 and 3 days ahead. Transit data analyses show a coefficient of correlation of 0.53 for a lag between precipitation and discharge of 1 day. On the other hand, temperature and discharge has a negative coefficient of correlation (-0.43) for a delay of 19 days. The ANNs developed provide a good result for the validation period, with R(2) between 0.92 and 0.80. Furthermore, these prediction models have been tested with discharge data from a period 16 years later. Results of this testing period also show a good correlation, with R(2) between 0.91 and 0.64. Overall, results indicate that ANNs are a good tool to predict river discharge with a small number of input variables.
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Modelos Teóricos , Redes Neurales de la Computación , Ríos/química , Contaminantes Químicos del Agua/química , Hidrología , EspañaRESUMEN
No disponible
Asunto(s)
Anciano de 80 o más Años , Femenino , Humanos , Urinálisis/instrumentación , Urinálisis/métodos , Urinálisis , Toma de Muestras de Orina/métodos , Micosis/diagnóstico , Micosis/microbiología , Micosis/orina , Micosis Fungoide/microbiología , Micosis Fungoide/cirugía , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/orina , Cromatografía de Gases y Espectrometría de Masas , Cloranfenicol/uso terapéuticoRESUMEN
Global cerebral ischemia induces selective acute neuronal injury of the CA1 region of the hippocampus. The type of cell death that ensues may include different programmed cell death mechanisms namely apoptosis and necroptosis, a recently described type of programmed necrosis. We investigated whether necroptosis contributes to hippocampal neuronal death following oxygen-glucose deprivation (OGD), an in vitro model of global ischemia. We observed that OGD induced a death receptor (DR)-dependent component of necroptotic cell death in primary cultures of hippocampal neurons. Additionally, we found that this ischemic challenge upregulated the receptor-interacting protein kinase 3 (RIP3) mRNA and protein levels, with a concomitant increase of the RIP1 protein. Together, these two related proteins form the necrosome, the complex responsible for induction of necroptotic cell death. Interestingly, we found that caspase-8 mRNA, a known negative regulator of necroptosis, was transiently decreased following OGD. Importantly, we observed that the OGD-induced increase in the RIP3 protein was paralleled in an in vivo model of transient global cerebral ischemia, specifically in the CA1 area of the hippocampus. Moreover, we show that the induction of endogenous RIP3 protein levels influenced neuronal toxicity since we found that RIP3 knock-down (KD) abrogated the component of OGD-induced necrotic neuronal death while RIP3 overexpression exacerbated neuronal death following OGD. Overexpression of RIP1 also had deleterious effects following the OGD challenge. Taken together, our results highlight that cerebral ischemia activates transcriptional changes that lead to an increase in the endogenous RIP3 protein level which might contribute to the formation of the necrosome complex and to the subsequent component of necroptotic neuronal death that follows ischemic injury.
Asunto(s)
Apoptosis/fisiología , Isquemia Encefálica/patología , Hipocampo/patología , Hipoxia/metabolismo , Neuronas/patología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Regulación hacia Arriba/fisiología , Animales , Anticuerpos/farmacología , Apoptosis/efectos de los fármacos , Isquemia Encefálica/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Maleato de Dizocilpina/farmacología , Embrión de Mamíferos , Glucosa/deficiencia , Hipocampo/citología , Hipoxia/patología , Imidazoles/farmacología , Indoles/farmacología , L-Lactato Deshidrogenasa/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Incorporation of biophysical and biochemical cues into the design of biomaterials is an important strategy for tissue engineering, the design of biomedical implants and cell culture. Hydrogels synthesized from poly(ethylene glycol) diacrylate (PEGDA) were investigated as a platform to simultaneously present human corneal epithelial cells (HCECs) in vitro with topography and adhesion peptides to mimic the native physical and chemical attributes of the basement membrane underlying the epithelium in vivo. Hydrogels synthesized from aqueous solutions of 20% PEGDA (M(w) = 3400 g/mol) prevented nonspecific cell adhesion and were functionalized with the integrin-binding peptide Arg-Gly-Asp (RGD) in concentrations from 5 to 20 mM. The hydrogels swelled minimally after curing and were molded with ridge and groove features with lateral dimensions from 200 to 2000 nm and 300-nm depth. HCECs were cultured on topographic surfaces functionalized with RGD and compared with control unfunctionalized topographic substrates. HCEC alignment, either parallel or perpendicular to ridges, was influenced by the culture media on substrates promoting nonspecific attachment. In contrast, the alignment of HCECs cultured on RGD hydrogels showed substantially less dependence on the culture media. In the latter case, the moldable RGD-functionalized hydrogels allowed for decoupling the cues from surface chemistry, soluble factors, and topography that simultaneously impact HCEC behavior.