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Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia. Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers. Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001). Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease.
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Gonorrhoea infections are frequently diagnosed at extragenital locations in asymptomatic individuals and are historically related to poor recovery in culture, which hinders antimicrobial susceptibility testing. The aim of this study was to evaluate recovery rates of Neisseria gonorrhoeae by culture among asymptomatic individuals who tested positive by nucleic acid amplification tests between 2018 and 2019 in Barcelona (Spain). In total, 10 396 individuals were tested for N. gonorrhoeae on first-void urine, rectal, pharyngeal and/or vaginal swabs depending on sexual behaviour. Overall infection prevalence was 5·5% (95% confidence interval [CI] 5·0-5·9). Seven hundred and ten samples were positive corresponding to 567 individuals. The most common site of infection was the pharynx (71·3%), followed by rectum (23·1%) and genitals (4·7%) (P < 0·0001). The N. gonorrhoeae recovery rate in culture, time from positive screening to culture specimen and inoculation delay were calculated. Recovery rate was 21·7% in pharynx, 66·9% in rectum and 37·0% in genitals (25·0% vagina, 71·4% urethra) (P < 0·0001). Median culture collection time was 1 [0; 3] days, and median inoculation delay was 5·01 [4·99-7·99] h, with no impact on N. gonorrhoeae recovery, P = 0·8367 and P = 0·7670, respectively. Despite efforts towards optimizing pre-analytical conditions, the N. gonorrhoeae recovery rate in asymptomatic individuals is unacceptably low (especially for pharynx), representing a problem for monitoring antimicrobial-resistant infections.
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Gonorrea , Neisseria gonorrhoeae , Femenino , Humanos , Neisseria gonorrhoeae/genética , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/prevención & control , Técnicas de Amplificación de Ácido Nucleico , Faringe , RectoRESUMEN
INTRODUCTION: The aim of the present study was to determine the contribution of the heme oxygenase (HO) system to the adaptation of the uteroplacental circulation to pregnancy in the rat, and its relationship with the maintenance of blood pressure during late gestation. METHODS: The HO inhibitor, stannous mesoporphyrin (SnMP), or vehicle were administered intraperitoneally to virgin and midpregnant rats. Mean arterial pressure (MAP) was measured before and after the treatment, in the conscious rats. Uterine and radial arteries blood flow velocities were obtained from pregnant rats at days 14 and 19 of gestation using high frequency ultrasonography. Trophoblast invasion and spiral arteries remodelling were analyzed in the mesometrial triangle of pregnant rats by immunohistochemistry. RESULTS: HO activity inhibition during late gestation induced a significantly increase in the MAP of pregnant rats (114 ± 1 mmHg vs 100 ± 2 mmHg, p < 0.05) but it did not affect this parameter in virgin rats (121 ± 2 mmHg vs 124 ± 3 mmHg). MAP elevation was associated with marked (p < 0.05) decreases in the systolic and diastolic flow velocities in uterine and radial arteries, as compared with pregnant control rats. Furthermore, spiral arteries of pregnant rats treated with SnMP showed lower (p < 0.001) proportion of lumen circumference covered by trophoblast (21 ± 3%) and a higher (p < 0.05) proportion of vascular smooth muscle (33 ± 5%) than control pregnant rats (59 ± 5% and 16 ± 5%, respectively) DISCUSSION: These data indicate that HO system play an important role in the adaptation of the uteroplacental circulation to pregnancy and in the blood pressure regulation during late gestation.
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Presión Sanguínea/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Circulación Placentaria/efectos de los fármacos , Trofoblastos/efectos de los fármacos , Remodelación Vascular/efectos de los fármacos , Animales , Arterias/efectos de los fármacos , Arterias/fisiología , Femenino , Hemodinámica/efectos de los fármacos , Metaloporfirinas/farmacología , Placenta/irrigación sanguínea , Embarazo , Ratas , Trofoblastos/fisiología , Útero/irrigación sanguínea , Remodelación Vascular/fisiologíaRESUMEN
Ethylcellulose nanoparticles have been obtained from O/W nano-emulsions of the water/polyoxyethylene 10 oleyl ether/[ethyl acetate+4wt% ethylcellulose] system by low energy-energy emulsification at 25°C. Nano-emulsions with droplet sizes below 200nm and high kinetic stability were chosen for solubilising dexamethasone (DXM). Phase behaviour, conductivity and optical analysis studies of the system have evidenced for the first time that both, the polymer and the drug play a role on the structure of the aggregates formed along the emulsification path. Nano-emulsion formation may take place by both, phase inversion and self-emulsification. Spherical polymeric nanoparticles containing surfactant, showing sizes below 160nm have been obtained from the nano-emulsions by organic solvent evaporation. DXM loading in the nanoparticles was high (>90%). The release kinetics of nanoparticle dispersions with similar particle size and encapsulated DXM but different polymer to surfactant ratio were studied and compared to an aqueous DXM solution. Drug release from the nanoparticle dispersions was slower than from the aqueous solution. While the DXM solution showed a Fickian release pattern, the release behaviour from the nanoparticle dispersions was faster than that expected from a pure Fickian release. A coupled diffusion/relaxation model fitted the results very well, suggesting that polymer chains undergo conformational changes enhancing drug release. The contribution of diffusion and relaxation to drug transport in the nanoparticle dispersions depended on their composition and release time. Surfactant micelles present in the nanoparticle dispersion may exert a mild reservoir effect. The small particle size and the prolonged DXM release provided by the ethylcellulose nanoparticle dispersions make them suitable vehicles for controlled drug delivery applications.
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Nanopartículas/química , Polímeros/química , Sistemas de Liberación de Medicamentos/métodos , EmulsionesRESUMEN
This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P < 0.05). This reduction in renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 µg/min vs. 72 ± 8 µg/min; P < 0.05) COX2np-treated rats. Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.
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Envejecimiento/fisiología , Angiotensina II/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Angiotensina II/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Hipertensión/fisiopatología , Riñón/metabolismo , Masculino , Proteinuria/metabolismo , Ratas , Ratas Sprague-Dawley , Caracteres SexualesRESUMEN
Objetivo: Valorar la sobrecarga férrica mediante el cálculo del valor T2* en el hígado y el miocardio en los pacientes con hemocromatosis secundaria. Evaluar la correlación de los valores obtenidos con los niveles de ferritina en sangre y la concentración de hierro hepático (CHH) calculada mediante resonancia magnética (RM), y la correlación de los valores T2* entre sí. Material y métodos: Se incluyeron 16 pacientes (13 varones y 3 mujeres), evaluados entre los anos 2008 y 2009, con una edad media de 61 anos. Quince eran pacientes politransfundidos y uno estaba diagnosticado de anemia sideroblástica hereditaria. Se estudió la ferritina en sangre, la CHH por RM, la función cardíaca mediante RM y el valor T2* mediante secuencias multieco en el hígado (TR/TE1/ TE/n◦ecos/ : 21/1,18/1.0/20/35◦) y el miocardio (26/1,04/0.8/30/60◦). Se realizó el análisis de correlación-regresión de los valores T2* cardíaco y hepático con los valores de ferritina y CHH, y entre sí. Resultados: Trece pacientes mostraron valores de ferritina superiores a 1.000 ng/ml (mediana/mínimo/máximo: 1.762/294/3.785 ng/ml). Trece pacientes presentaron CHH elevada, mayor de 80 mol/g (mediana/mínimo/máximo: 125,4/41,2/241,5 mol/g). En todos los casos la función cardíaca estaba preservada. En 15 pacientes el valor T2* hepático fue menor de 6,3 ms. Solo en un caso, el valor T2*miocárdico fue menor de 20 ms. Se observó una alta correlación para los valores T2*hepático/CHH (r: -0,912). La correlación fue estadísticamente significativa para T2* hepático/ferritina (r: -0,541). La correlación T2*miocárdico/ferritina, T2*miocárdico/CHH y T2*miocárdico/T2*hepático no fue estadísticamente significativa. Conclusión: Los valores T2* hepático muestran una alta correlación con la CHH y una correlación estadísticamente significativa con la ferritina. No se observó correlación entre los valores T2* miocárdico y la ferritina en sangre, la CHH, ni con el valor T2* hepático (AU)
Objective: To determine whether there is iron overload by calculating the T2* value in the liver and myocardium in patients with secondary haemochromatosis. To analyse the correlation of the values obtained with the iron levels in blood, with the liver iron concentration (LIC) calculated using magnetic resonance (MR) imaging, and the correlation between them. Material and methods: A total of 16 patients (13 males, 3 females), with a mean age of 61 years, were included and evaluated in the years 2008 and 2009. Fifteen of them had received multiple transfusions, and one was diagnosed with hereditary sideroblastic anaemia. The measurements included, blood ferritin, LIC by MRI, cardiac function using MRI and the T2* value by means of multi-echo sequences in the liver (TR/TE1/ TE/No of echos/ : 21/1,18/1.0/20/35◦) and myocardium (26/1.04/0.8/30/60◦). A correlation-regression analysis was performed by comparing the cardiac and liver T2* values with the ferritin, LIC and between each of them. Results: A total of 13 patients had ferritin values greater than 1000 ng/ml (median/minimum/maximum: 1762/294/3785 ng/ml). An increased LIC greater than 80 mol/g (median/minimum/maximum: 125.4/41.2/241.5 mol/g) was observed in 13 patients. In all cases cardiac function was conserved, and in 15 cases the liver T2* value was less than 6.3 ms. The myocardium T2* value was less than 20 ms. in only one case. A high correlation was observed between the liver T2* values and the LIC (r: -0.912). The correlation was statistically significant between the liver T2* value and ferritin (r: -0.541). The correlations between myocardium T2* and ferritin, myocardium T2* and LIC, and myocardium T2* and liver T2* were not statistically significant. Conclusions: The liver T2* showed a high correlation with LIC and a statistically significant correlation with ferritin. No association was observed between the myocardium T2* values and ferritin in blood, the LIC or the liver T2* value (AU)
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Humanos , Masculino , Femenino , Isquemia/complicaciones , Isquemia/diagnóstico , Colitis Isquémica , Abdomen Agudo/complicaciones , Abdomen Agudo , /métodos , Estudios Retrospectivos , Enfermedades Vasculares Periféricas , Tomografía Computarizada Espiral/métodos , Tomografía Computarizada EspiralRESUMEN
OBJECTIVES: To evaluate the analgesic effect as well as patient cooperation and satisfaction with sub-tenon's anesthesia in glaucoma surgery. MATERIAL AND METHODS: Prospective uncontrolled study. Fifty-three patients who underwent glaucoma surgery, with or without cataract extraction, with sub-Tenon's anesthesia have been studied. Satisfaction and cooperation were evaluated on a qualitative scale. The pain level was quantified using a numerical scale from 1 (no pain) to 10 (unsupportable pain). RESULTS: The mean pain score at the different periods was: 2.13 (standard deviation [SD] 1.47) on administering anesthesia, 1.74 (SD 1.27) during the surgery, 1.63 SD (1.23) immediately after the procedure, 1.38 (SD 0.38) 30 min later, and 1.38 (SD 0.63) when leaving the recovery unit. The postoperative satisfaction was "fairly or very satisfied" in 92.6% of the cases for both the surgeons and the patients. Twenty-four patients complained during the surgery, 15 of them at the conjunctival suture; in these cases additional anesthesia was administered, and, in 4 cases, intravenous paracetamol was given. Pain scores were significatively higher during the surgery (P=.033), and immediately after the procedure (P=.027) in trabeculectomy than in deep sclerectomy patients. CONCLUSIONS: The good analgesic level reached led to a high level of patient and surgeon satisfaction, even in longer procedures such as deep sclerectomy combined with cataract extraction, or implantation of drainage devices. Pain scores were significatively higher in trabeculectomy than in deep sclerectomy patients.
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Anestesia Local/métodos , Glaucoma/cirugía , Satisfacción en el Trabajo , Satisfacción del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Conducta Cooperativa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cápsula de TenonRESUMEN
Objetivos: Valorar el efecto analgésico así como la colaboración y satisfacción de los pacientes en la cirugía de glaucoma con anestesia subtenoniana. Material y métodos: Estudio prospectivo no controlado. Se estudiaron datos de 53 pacientes operados de glaucoma, asociado o no a cirugía de catarata, bajo anestesia subtenoniana, valorándose de manera cualitativa la satisfacción y colaboración, así como el grado de analgesia mediante una escala numérica de 1 (no dolor) a 10 (máximo). Resultados: La calificación media del dolor ha sido: 2,13 desviación estándar (DE): 1,47 al administrar la anestesia, 1,74 DE: 1,27 durante la intervención, 1,63 DE: 1,23 en el postoperatorio inmediato, 1,38 DE: 0,38 a los 30min y 1,38 DE: 0,63 al alta. El grado de satisfacción fue «bastante o muy satisfecho» en el 92,6% de los casos, tanto para pacientes como para cirujanos. En 24 casos el paciente refirió molestias, 15 de ellos durante la sutura conjuntival, requiriendo anestesia adicional y en cuatro casos, paracetamol sistémico. La puntuación del dolor fue significativamente mayor durante la cirugía (p=0,033) y en el postoperatorio inmediato (p=0,027) en los pacientes operados de trabeculectomía que en la esclerectomía profunda no penetrante (EPNP). Conclusiones: El buen nivel analgésico conseguido favoreció un alto grado de satisfacción por parte de cirujanos y pacientes, incluso en procedimientos de larga duración como esclerectomía profunda no penetrante combinada con facoemulsificación e implantes de dispositivos de drenaje. El dolor percibido por los pacientes durante la cirugía y postoperatorio inmediato fue mayor en la trabeculectomía que en la EPNP(AU)
Objectives: To evaluate the analgesic effect as well as patient cooperation and satisfaction with sub-tenon's anesthesia in glaucoma surgery. Material and methods: Prospective uncontrolled study. Fifty-three patients who underwent glaucoma surgery, with or without cataract extraction, with sub-Tenon's anesthesia have been studied. Satisfaction and cooperation were evaluated on a qualitative scale. The pain level was quantified using a numerical scale from 1 (no pain) to 10 (unsupportable pain). Results: The mean pain score at the different periods was: 2.13 (standard deviation [SD] 1.47) on administering anesthesia, 1.74 (SD 1.27) during the surgery, 1.63 SD (1.23) immediately after the procedure, 1.38 (SD 0.38) 30min later, and 1.38 (SD 0.63) when leaving the recovery unit. The postoperative satisfaction was fairly or very satisfied in 92.6% of the cases for both the surgeons and the patients. Twenty-four patients complained during the surgery, 15 of them at the conjunctival suture; in these cases additional anesthesia was administered, and, in 4 cases, intravenous paracetamol was given. Pain scores were significatively higher during the surgery (P=.033), and immediately after the procedure (P=0.027) in trabeculectomy than in deep sclerectomy patients. Conclusions: The good analgesic level reached led to a high level of patient and surgeon satisfaction, even in longer procedures such as deep sclerectomy combined with cataract extraction, or implantation of drainage devices. Pain scores were significatively higher in trabeculectomy than in deep sclerectomy patients(AU)
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Humanos , Glaucoma/cirugía , Anestesia/métodos , Dolor Postoperatorio/epidemiología , Estudios Prospectivos , Cápsula de Tenon , Satisfacción del Paciente , Extracción de Catarata/métodos , Facoemulsificación/métodosRESUMEN
Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT(1) receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT(1) receptor antagonist (ARAnp) during the nephrogenic period. ARAnp-treated rats were hypertensive, but an age-dependent rise in AP was only found in males. Three days of treatment with candesartan (7 mg·kg(-1)·day(-1)) led to a fall of AP that was greater (P < 0.05) in male than in female 10- to 11-mo-old ARAnp-treated rats. Oxidated proteins were elevated (P < 0.05), and the decrease in AP elicited by candesartan was reduced (P < 0.05) when these rats are also treated with tempol (18 mg·kg(-1)·day(-1)). Hypertension was not maintained by an elevation of AT(1) receptors in kidneys and mesenteric arteries. The acute renal hemodynamic response to ANG II (30 ng·kg(-1)·min(-1)) was similarly enhanced (P < 0.05) in both sexes of ARAnp-treated rats at 3-4 but not at 10-11 mo of age. Our results suggest that an adverse event during the nephrogenic period induces an ANG II-dependent increment in AP that is aggravated only in males during aging and that oxidative stress but not an increase in AT(1) receptor contributes to the rise in AP. This study also shows that the renal hemodynamic sensitivity to ANG II is transitorily enhanced in both sexes of rats with altered renal development.
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Angiotensina II/fisiología , Presión Arterial , Riñón/crecimiento & desarrollo , Envejecimiento/fisiología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Presión Arterial/efectos de los fármacos , Bencimidazoles/farmacología , Compuestos de Bifenilo , Femenino , Riñón/efectos de los fármacos , Masculino , Arterias Mesentéricas/fisiopatología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/fisiología , Caracteres Sexuales , Tetrazoles/farmacologíaRESUMEN
OBJECTIVE: The aims of this review are to describe the main characteristics for the CT diagnosis of isolated caecal ischaemia (ICA) and give details of the differential diagnosis with other conditions with a similar clinical picture. MATERIAL AND METHODS: A retrospective study was conducted to review the CT findings of 4 patients diagnosed with ICA in our hospital. The parameters recorded to analyse their characteristics in the CT were: maximum thickness of the caecum wall, the appearance of the peri-caecum fat, presence of free fluid, signs of caecal or portal pneumatosis, the appearance of the caecal appendix, and general signs of the presence of vasculopathy. RESULTS: In all cases it was recorded that there was a thickening of the walls of the blind loop with an abrupt transition between the caecal wall and the walls of the ascending colon wall. In all cases the caecal thickening had a characteristic image in the central area. Signs of caecal pneumatosis were observed in two cases. All of them had an appendix with normal characteristics. CONCLUSIONS: The combination of caecal wall thickening with oedematous characteristics, with no changes in the appendix, ileum and colon, suggest the diagnosis of caecal ischaemia, particularly with the presence of pneumatosis.
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Ciego/irrigación sanguínea , Isquemia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
La colonografía por TC fue aceptada por la American Cancer Society en el 2008 como técnica de cribado para el cáncer colorrectal. Este hecho debe considerarse un gran paso en el reconocimiento de la técnica, que aun siendo relativamente nueva está cambiando ya algunos algoritmos diagnósticos. En esta actualización sobre colonografía por TC se describen los parámetros de calidad que hacen a una colonografía por TC diagnóstica y se revisan las innovaciones técnicas y de preparación colónica. Se apunta, aunque brevemente, un recordatorio de la semiología, y se discute, para finalizar, el estado actual de sus indicaciones, incidiendo en las controversias actuales (AU)
In 2008, CT colonography was approved by the American Cancer Society as a technique for screening for colorectal cancer. This approval should be considered an important step in the recognition of the technique, which although still relatively new is already changing some diagnostic algorithms. This update about CT colonography reports the quality parameters necessary for a CT colonographic study to be diagnostic and reviews the technical innovations and colonic preparation for the study. We provide a brief review of the signs and close with a discussion of the current indications for and controversies about the technique (AU)
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Humanos , Masculino , Femenino , Radiología/educación , Radiología , Servicio de Radiología en Hospital , Colonografía Tomográfica Computarizada/métodos , Colonografía Tomográfica Computarizada , Neoplasias Colorrectales , Tomografía Computarizada por Rayos X/tendencias , Colon/patología , ColonRESUMEN
In 2008, CT colonography was approved by the American Cancer Society as a technique for screening for colorectal cancer. This approval should be considered an important step in the recognition of the technique, which although still relatively new is already changing some diagnostic algorithms. This update about CT colonography reports the quality parameters necessary for a CT colonographic study to be diagnostic and reviews the technical innovations and colonic preparation for the study. We provide a brief review of the signs and close with a discussion of the current indications for and controversies about the technique.
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Enfermedades del Colon/diagnóstico por imagen , Colonografía Tomográfica Computarizada , Colonografía Tomográfica Computarizada/métodos , Colonografía Tomográfica Computarizada/normas , Humanos , Programas InformáticosRESUMEN
Cyclooxygenase 2 (COX2) is involved in regulating renal hemodynamics after renal ablation. It is also known that high protein intake (HPI) leads to a deterioration of renal function when there is preexisting renal disease and that there are important gender differences in the regulation of renal function. This study tested the hypothesis that the role of COX2 in regulating renal function and the renal hemodynamic effects elicited by HPI are enhanced when nephrogenesis is altered during renal development. It was also expected that the role of COX2 and the effects elicited by HPI are age and sex dependent. Newborn Sprague-Dawley rats were treated with an AT(1) ANG II receptor antagonist during the nephrogenic period (ARAnp). Experiments were performed at 3-4 and 10-11 mo of age. Arterial pressure was elevated (P < 0.05) at both ages and in both sexes of ARAnp-treated rats. Renal COX2 expression was only elevated (P < 0.05) at 10-11 mo of age in both sexes of ARAnp-treated rats. COX2 inhibition induced greater renal vasoconstriction in male and female hypertensive than in normotensive rats at both ages. HPI did not induce glomerular filtration rate (GFR) in the youngest hypertensive rats and in the oldest female hypertensive rats. However, the GFR decreased during HPI (0.63 ± 0.07 to 0.19 ± 0.05 ml/min) in the oldest male hypertensive rats. The HPI-induced increment in proteinuria was greater (P < 0.05) in male (99 ± 22 mg/day) than in female (30 ± 8 mg/day) hypertensive rats. These results show that COX2 plays an important role in the regulation of renal function when renal development is altered and that prolonged HPI can lead to a renal insufficiency in males but not in females with reduced nephron endowment.
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Ciclooxigenasa 2/metabolismo , Proteínas en la Dieta/efectos adversos , Riñón/enzimología , Organogénesis , Insuficiencia Renal/etiología , Animales , Animales Recién Nacidos , Inhibidores de la Ciclooxigenasa 2/farmacología , Femenino , Riñón/crecimiento & desarrollo , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Caracteres SexualesRESUMEN
PURPOSE: The main objectives of enucleation, evisceration or secondary orbital implants are to replace orbital volume and obtain good motility and adaptation of the implant and the external prosthesis. We describe our experience using autologous dermis graft sutured to Tenon and conjunctiva following evisceration, enucleation and any reconstruction requiring either a primary or secondary orbital implant, even those with large tissue loss. MATERIALS AND METHODS: A retrospective case series of patients who received an autologous dermis graft to assist in closure of a Tenon's capsule and conjunctiva at the time of placement of secondary orbital implants or evisceration or enucleation with fornices retraction or tension in tissues. We also describe how and from where to take the dermis graft. RESULTS: 72 patients were included and all received orbital porous polyethylene implants: 28 patients had secondary orbital implants, 36 patients had evisceration and 8 patients had enucleation. Implant size was 20 mm in most cases, but went to 22 mm. Follow-up ranged from 3 to 36 months. No intraoperative complications were observed in donor or receptor area. 8 cases had incipient ischemia of the dermis graft, but were treated and resolved with autologous serum. CONCLUSIONS: Implant exposure is due to bad surgical technique, an inadequate implant size or excessive tension on the suture. Dermis autologous graft allows moving the orbital implant anteriorly because it replaces surface to suture Tenon and conjunctiva without tension, so a good adaptation of a thinner external prosthesis is possible, resulting in better motility.
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Órbita/cirugía , Implantes Orbitales , Procedimientos de Cirugía Plástica/métodos , Trasplante de Piel/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anoftalmos/cirugía , Estudios de Cohortes , Estética , Enucleación del Ojo , Evisceración del Ojo , Ojo Artificial , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis/métodos , Estudios Retrospectivos , Medición de Riesgo , Trasplante Autólogo/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
El cáncer de recto es una neoplasia con elevada incidencia en nuestro medio. Las distintas opciones terapéuticas que podrán aplicarse en cada caso van a depender fundamentalmente de la extensión que presente el tumor en el momento del diagnóstico. Por esto, los radiólogos tenemos un papel central en su tratamiento. En el presente texto se discuten la técnica radiológica óptima, algunos aspectos anatómicos fundamentales y la semiología aceptada en la interpretación de los distintos estudios de imagen que se realizan a estos pacientes, además de su rendimiento, y una visión general del pronóstico y de las distintas opciones terapéuticas. Su conocimiento es muy útil para participar en equipos formados por diferentes especialistas y comprender la trascendencia de la información aportada por la interpretación de los estudios que realizamos a estos pacientes (AU)
Rectal cancer has a high incidence in our area. The different treatment options that can be used in each case depend fundamentally on the extension of the tumor at the time of diagnosis. Thus, radiologists have a central role in the management of this disease. We discuss the optimum imaging technique for staging rectal cancer, some fundamental histological aspects, and the accepted semiology in the interpretation of different imaging studies carried out in these patients, as well as the diagnostic performance of each technique. We provide a general overview of the prognosis and different treatment options. This knowledge is very useful for radiologists participating in multidisciplinary teams and for understanding the transcendence of the information provided by image interpretation in these patients (AU)
Asunto(s)
Humanos , Masculino , Femenino , Estadificación de Neoplasias/métodos , Estadificación de Neoplasias , Neoplasias del Recto/clasificación , Neoplasias del Recto/diagnóstico , Recto/patología , Recto , Ganglios Linfáticos , España/epidemiología , Canal Anal/patología , Canal Anal , Neoplasias del Ano , Neoplasia Residual , Quimioterapia Adyuvante , Radioterapia Adyuvante , EndoscopíaRESUMEN
Rectal cancer has a high incidence in our area. The different treatment options that can be used in each case depend fundamentally on the extension of the tumor at the time of diagnosis. Thus, radiologists have a central role in the management of this disease. We discuss the optimum imaging technique for staging rectal cancer, some fundamental histological aspects, and the accepted semiology in the interpretation of different imaging studies carried out in these patients, as well as the diagnostic performance of each technique. We provide a general overview of the prognosis and different treatment options. This knowledge is very useful for radiologists participating in multidisciplinary teams and for understanding the transcendence of the information provided by image interpretation in these patients.
Asunto(s)
Neoplasias del Recto/patología , Humanos , Estadificación de Neoplasias/métodos , Pronóstico , Neoplasias del Recto/terapiaRESUMEN
We have demonstrated that the reduction of angiotensin II effects during the nephrogenic period reduces the nephron number and induces the development of hypertension. The hypotheses examined are that this reduction of angiotensin effects leads to the development of an age-dependent sodium sensitive hypertension and that the hypertension is angiotensin II dependent. Newborn rats were treated with an angiotensin II type 1 receptor antagonist during the first 2 weeks of age. At 3 to 4 and 11 to 12 months of age, changes in systolic blood pressure, proteinuria, and renal function in response to a prolonged high sodium intake were examined. The basal blood pressure response to the administration of the angiotensin II receptor antagonist was also evaluated at both ages. Basal blood pressure was similarly elevated (P<0.05) in male and female treated rats, and the increment was age dependent. High sodium intake only elicited a blood pressure elevation (136+/-1 to 154+/-3 mm Hg; P<0.05) and a decrease in glomerular filtration rate (28%; P<0.05) at 11 to 12 months in treated rats. Blockade of angiotensin II receptors during renal development induced an increase (P<0.05) in proteinuria that was age and sex dependent, but high sodium intake only induced an elevation in proteinuria in the younger rats (50%; P<0.05). Hypertension was maintained by angiotensin II at both ages because blood pressure decreased to normal levels after treatment with an angiotensin II type 1 receptor antagonist. This study shows that the reduction of angiotensin II effects during the nephrogenic period modifies renal function and induces the development of an angiotensin II-dependent hypertension that becomes sodium sensitive during aging.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Hipertensión Renal/patología , Nefronas/efectos de los fármacos , Nefronas/patología , Cloruro de Sodio Dietético/farmacología , Factores de Edad , Angiotensina II/metabolismo , Animales , Animales Recién Nacidos , Proteínas en la Dieta/farmacología , Modelos Animales de Enfermedad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión Renal/inducido químicamente , Hipertensión Renal/tratamiento farmacológico , Masculino , Nefronas/crecimiento & desarrollo , Proteinuria/patología , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/metabolismo , Factores SexualesRESUMEN
Functional genomics approaches are indispensable tools in the drug discovery arena and have recently attained increased attention in antibacterial drug discovery research. However, the application of functional genomics to post-genomics research of Plasmodia is still in comparatively early stages. Nonetheless, with this genus having the most species sequenced of any eukaryotic organism so far, the Plasmodia could provide unique opportunities for the study of intracellular eukaryotic pathogens. This review presents the status quo of functional genomics of the malaria parasite including descriptions of the transcriptome, proteome and interactome. We provide examples for the in silico mining of the X-ome data sets and illustrate how X-omic data from drug challenged parasites might be used in elucidating amongst others, the mode-of-action of inhibitory compounds, validate potential targets and discover novel targets/therapeutics.
Asunto(s)
Antimaláricos , Diseño de Fármacos , Genómica , Malaria/tratamiento farmacológico , Plasmodium/efectos de los fármacos , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Perfilación de la Expresión Génica , Humanos , Malaria/parasitología , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteoma , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
The aim was to evaluate whether blockade of ANG II effects during renal development modifies the renal response to an increment of plasma amino acid concentration. It was also examined in anesthetized rats whether the reduction of the renal ability to eliminate an acute volume expansion (VE), elicited by blockade of ANG II during renal development, is sex and/or age dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT(1)-receptor antagonist (ARA) during postnatal nephrogenesis. Amino acid infusion induced increments (P < 0.05) of glomerular filtration rate (31 +/- 6%) and renal plasma flow (26 +/- 5%) in male but not in female vehicle-treated rats. Natriuretic and diuretic responses to amino acid infusion were similar in male and female vehicle-treated rats. These renal hemodynamics and excretory responses to amino acid infusion were abolished in ARA-treated rats. Renal responses to VE were evaluated at 3-4 and 9-10 mo of age in vehicle and ARA-treated rats. VE-induced natriuresis and diuresis were reduced by more than 38% (P < 0.05) in 3- to 4-mo-old male and female ARA-treated rats. An age-dependent reduction (P < 0.05) in the renal ability to eliminate VE was found in male but not in female rats treated with ARA. Our results demonstrate that the renal effects induced by an increment in amino acids are abolished when ANG II effects have been reduced during nephrogenesis. In addition, this reduction of ANG II effects elicits an impairment of the renal ability to eliminate an acute VE in males and females, which is aggravated by age only in male rats.
Asunto(s)
Angiotensina II/sangre , Riñón/irrigación sanguínea , Riñón/crecimiento & desarrollo , Circulación Renal/fisiología , Factores de Edad , Aminoácidos/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Animales Recién Nacidos , Volumen Sanguíneo/fisiología , Diuresis/efectos de los fármacos , Diuresis/fisiología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Soluciones Isotónicas/farmacología , Masculino , Natriuresis/efectos de los fármacos , Natriuresis/fisiología , Embarazo , Ratas , Ratas Sprague-Dawley , Circulación Renal/efectos de los fármacos , Factores SexualesRESUMEN
This study was designed to test the hypothesis that blockade of angiotensin II effects during renal development accelerates the aging-related changes in renal hemodynamics and proteinuria, and that these changes are sex dependent. It has also been examined whether the deterioration of urinary concentrating ability elicited by angiotensin II blockade is sex and/or aging dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT(1) angiotensin II receptor antagonist (ARA) during the first 14 postnatal days. Blood pressure, glomerular filtration rate, proteinuria, and urinary concentrating ability in response to dehydration were examined in conscious rats at 3 and 11 mo of age. ARA treatment elicited a similar increment in blood pressure in males and females that was greater (P < 0.05) at 11 than at 3 mo of age. Glomerular filtration rate only decreased (P < 0.05) in 11-mo-old male ARA-treated rats (0.59 +/- 0.07 vs. 0.80 +/- 0.07 ml.min(-1).g(-1) in control group). At 3 mo of age, proteinuria increased in male (107%) but not in female ARA-treated rats. However, at 11 mo of age, proteinuria increased in both sexes, but the increment was greater (P < 0.05) in male (244%) than in female (138%) ARA-treated rats. Renal ability to concentrate urine in response to prolonged water dehydration was only reduced in ARA-treated males. The reduction of urinary concentrating ability was accentuated by aging. Therefore, we conclude that blockade of angiotensin II effects during renal development elicits an important deterioration of cortical and medullary function that is sex and aging dependent.