Foliar applications of zinc oxide nanoparticles and boric acid affect leaf oxidative metabolism and productivity in young pecan trees.

Zinc and boron are nutrients that often suffer low bioavailability to pecan trees grown in calcareous soils whereas adequate supplies of these two elements is essential for commercial pecan production. Working with young pecan trees, we evaluated changes in oxidative metabolism, levels of bioactive compounds, yield components and foliar nutrient concentrations in response to foliar sprays (50 or 100 mg L-1) of zinc oxide nanoparticles (ZnO NPs) and boron (H3BO3). Four different treatment solutions were applied in a completely randomised design with six replications per treatment (24 trees in total). Zinc and B treatments were applied before pistil receptivity (3 weeks before anthesis) and at stem elongation stage 31, 39/60; flowering stage 69; fruit stages 7-75 and continued for a total of five applications at 14-day intervals. We evaluated enzyme activities (SOD, H2O2, CAT and GPx), AC, phenols, flavonoids, leaf area, chlorophyll, total anthocyanins and nut yield and quality (nut weight and % kernel). The mineral concentrations in the leaflets were also determined. The mineral concentrations (N, P, K, Ca, Mg, Fe, Cu, Mn, Ni, Zn and B) in the leaflets were also determined. Spraying ZnO NPs and B increased SOD activity, CA, chlorophyll concentration, mineral nutrients (N, K, Ca, Zn and B) and yield. However, reductions were observed for CAT activity, nut quality and concentrations of phenol, flavonoid, anthocyanin and Fe. Boron increased GPx activity and P concentration. These results demonstrate that spraying low doses (50 mg L-1) of ZnO NPs and B can help reduce oxidative stress and increase yield, nut quality and leaf concentrations of Zn and B in young cv. Wichita pecan trees established on a calcareous soil.

Aproximación para establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes infectados con virus de hepatitis C, revisión estructurada (actualización 2015-2017) / Structured review of establishing and evaluating clinical relevance of drug interactions in hepatitis C virus treatment (Update 2015 - 2017)

Resumen Objetivo: establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes con hepatitis C. Método: se realizó una búsqueda en PubMed/MedLine de artículos publicados en inglés y en español, desde el 1 de enero de 2015 hasta el 30 de marzo de 2017, utilizando los términos Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, de estudios realizados en humanos. La relevancia clínica de las interacciones medicamentosas se estableció y evaluó con base en la probabilidad de ocurrencia y la gravedad de la interacción. Resultados: se identificaron 184 artículos, de los cuales 92 se seleccionaron por el título y resumen para revisión completa, a 2 de ellos no fue posible acceder al texto completo. De estos, 57 aportaban interacciones, lo que permitió identificar 155 parejas de interacciones medicamentosas, de las cuales 154 (99,4 %) fueron farmacocinéticas y 1 (0,6 %) farmacodinámica. Por su parte, de las 155 parejas, 34 (21,9 %) se valoraron de nivel 1; 73 (47,1 %) de nivel 2; 48 (31,0 %) de nivel 3; y 0 (0,0 %) de nivel 4. Además, se identificaron 29 parejas agrupadas como interacciones con evidencia de ausencia de relevancia clínica. Conclusiones: más de 99 % de las interacciones medicamentosas de relevancia clínica son farmacocinéticas, asociadas con cambios en el metabolismo y el transporte de fármacos; el simeprevir y la terapia 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) fueron los medicamentos con mayor número de interacciones.

Abstract Objective: This study-s objective is to establish and evaluate the clinical relevance of drug interactions during treatment of patients with hepatitis C. Method: A PubMed/MedLine search was conducted for articles published in English and Spanish from January 1, 2015 to March 30, 2017 using the terms Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, from studies conducted in humans. The clinical relevance of drug interactions was established and evaluated based on probability of occurrence and severity of interactions. Results: Of the 184 four articles identified, 92 were selected by title and abstract for full review. The full texts of two articles could not be accessed. Of the remaining articles, 57 describ ed relevant interactions. Of the 155 pairs of drugs that interact that were identified, 154 (99.4%) were pharmacokinetic, and one (0.6%) was pharmacodynamic. Thirty-four of the 155 pairs (21.9%) were assessed at level 1; 73 (47.1%) were assessed at level 2; 48 (31.0%) were assessed at level 3, none were assessed at level 4. In addition, 29 pairs of interacting drugs had no evidence of clinical relevance. Conclusions: More than 99% of clinically relevant drug interactions are pharmacokinetics and are associated with changes in metabolism and transport of drugs. Simeprevir and 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) therapy had the greatest number of interactions.

Study of the interaction between cisplatin and the Au18(SR)14 cluster: in search of an appropriate cisplatin carrier.

Cisplatin is a well known anti-cancer drug and considered as essential by the World Health Organization. However, cisplatin features side effects during medical treatments due to its lack of selectivity resulting in the indiscriminate death of cells including healthy cells. To solve this issue, it is mandatory to improve its delivery towards affected organs or tissues. The well known bio-compatibility of gold clusters encouraged us to study the interaction between cisplatin molecules and the Au18(SR)14 cluster (named Au18) and our DFT calculations have provided insight into this aspect. Calculated adsorption energy values of the cisplatinn/Au18 complexes are within the 0.5-3.6 eV range, which attests to their unique interaction. In addition, their calculated optical absorption (UV-vis) and circular dichroism (CD) spectra display distinct peaks in such a manner that UV/CD spectra can be used as fingerprints by experimentalists.

Evaluación clínica del paciente con síntomas del tracto urinario inferior / Clinical evaluation of the patient with lower urinary tract symptoms

Lower urinary tract symptoms are divided into three groups, storage, voiding and post micturition symptoms. Their level of agreement with urodynamic investigation is poor. Clinicalhistory should be complemented by the application of validated symptom questionnaires and the recording of urinary events. Here we refer to: a) the International Consultation onIncontinence Questionnaire, Short Form (ICIQ-SF), b) the Urogenital Distress Inventory - Short Form (UDI-6) and Incontinence Impact Questionnaire – Short Form (IIQ-7), c) the urinary incontinence Severity Index and d) the American Urological Association Symptom Index. The recordings of urinary events can be done in three main forms: a) micturition time chart, b)frequency volume chart, and c) bladder diary. The International Consultation on Incontinence Questionnaire bladder diary (ICIQ bladder diary) is the only one validated. Physical exam should include abdominal and genital examination, covering pelvic organ prolapse quantification in women, prostate evaluation in men, pelvic floor muscle function evaluation in both genders, and a neurologic examination focused on evaluation of the sacral nerves. It is useful to supplementthe physical examination with the evaluation of the mobility of the bladder neck and proximal urethra through the Q-tip test, and with the quantification of urine leakage through the pad test.

[Coverage of diagnostic upper gastrointestinal endoscopy for the prevention of gastric cancer in Chile: results from the 2009-2010 National Health Survey]. / Cobertura de la estrategia preventiva de cáncer gástrico en Chile: resultados de la Encuesta Nacional de Salud 2009-2010.

BACKGROUND: In Chile, gastric cancer (GC) is a major cause of cancer related deaths. The current screening strategy consists of an upper gastrointestinal endoscopy (UGE) for people aged 40 years or more with epigastric pain. AIM: To evaluate the diagnostic coverage of the use of UGE for early detection of GC in Chile. MATERIAL AND METHODS: As part of the digestive module of the 2009-10 National Health Survey, 5293 adults over 15 years were asked about the presence of epigastric pain, possible upper gastrointestinal bleeding (PUGB), use of proton pump inhibitors (PPIs) or histamine H2-receptor antagonists (H2RAs), family history of GC and having performed an UGE. RESULTS: Persistent epigastric pain was observed in 3.4% of the population. PUGB signs were observed in 3.3% of the population. The prevalence of PPIs and H2RAs use was 4.3% and 2.2% respectively, reaching 21.6% in people aged 70 years and older. Life span prevalence of UGE was 18.3%, with differences by region, health insurance and educational level. UGE coverage in people aged 40 years or older with and without persistent epigastric pain was 14.4% and 3.2% respectively (Odds ratio 4.8, p < 0.01). The prevalence of UGE was similar among people with or without PUGB or family history of CG. CONCLUSIONS: The estimated coverage of the current GC prevention strategy in Chile is 14.4%, evaluated at a population level. Further studies are required to determine the impact of this strategy on early GC diagnosis and mortality.

Cobertura de la estrategia preventiva de cáncer gástrico en Chile: resultados de la Encuesta Nacional de Salud 2009-2010 / Coverage of diagnostic upper gastrointestinal endoscopy for the prevention of gastric cancer in Chile: results from the 2009-2010 National Health Survey

Background: In Chile, gastric cancer (GC) is a major cause of cancer related deaths. The current screening strategy consists of an upper gastrointestinal endoscopy (UGE) for people aged 40 years or more with epigastric pain. Aim: To evaluate the diagnostic coverage of the use of UGE for early detection of GC in Chile. Material and Methods: As part of the digestive module of the 2009-10 National Health Survey, 5293 adults over 15 years were asked about the presence of epigastric pain, possible upper gastrointestinal bleeding (PUGB), use of proton pump inhibitors (PPIs) or histamine H2-receptor antagonists (H2RAs), family history of GC and having performed an UGE. Results: Persistent epigastric pain was observed in 3.4% of the population. PUGB signs were observed in 3.3% of the population. The prevalence of PPIs and H2RAs use was 4.3% and 2.2% respectively, reaching 21.6% in people aged 70 years and older. Life span prevalence of UGE was 18.3%, with differences by region, health insurance and educational level. UGE coverage in people aged 40 years or older with and without persistent epigastric pain was 14.4% and 3.2% respectively (Odds ratio 4.8, p < 0.01). The prevalence of UGE was similar among people with or without PUGB or family history of CG. Conclusions: The estimated coverage of the current GC prevention strategy in Chile is 14.4%, evaluated at a population level. Further studies are required to determine the impact of this strategy on early GC diagnosis and mortality.

[Origin of surgical metastatic bone disease]. / Origen de la enfermedad ósea metastática quirúrgica.

BACKGROUND: Metastatic bone disease should be considered as a public health problem. The alterations it may cause include pain that is refractory to medical treatment, metabolic instability, pathologic fractures and spinal disorders. MATERIAL AND METHODS: The primary tumor site that led to the need for surgery was investigated in a series of patients with a diagnosis of metastatic bone disease. The bone involved and the histology of the lesions were also studied. RESULTS: Kidney cancer was the one that most frequently required a surgical procedure; it was followed by breast and prostate cancer. The primary tumor was not found in 6.36% of cases. The bones affected by the lesions studied were as follows in order of occurrence: femur, spine, humerus and pelvis. Adenocarcinoma was the most frequent histological diagnosis. DISCUSSION: The diagnosis of metastatic bone disease should always be considered in patients over forty years of age with skeletal lesions, preferably lytic. CONCLUSIONS: In this study, kidney cancer, the proximal limbs and adenocarcinomas were the variables that most frequently produced metastatic bone lesions that warranted a surgical procedure.

Expresión de los receptores hormonales (RE/RP) y sobreexpresión de la proteína HER-2/neu en carcinoma ductal infiltrante / Expression of hormone receptors receptors (ER/RP) and overexpression of HER-2/neu protein overexpression in infiltrating ductal carcinoma

Introducción: El grado de diferenciación tumoral, la expresión de los receptores de estrógeno y progesterona y la sobreexpresión de la proteína HER-2/neu son factores de tipo pronóstico y predictivo importantes en la evolución y conducta terapéutica del carcinoma mamario infiltrante. Se ha encontrado en diversos estudios que los inmunofenotipos que no expresan los receptores hormonales o que sobre expresan la proteína HER-2/neu se asocian con pobre diferenciación tumoral. Objetivo: Determinar el perfil inmunofenotípico del carcinoma ductal infiltrante y establecer su relación con el grado de diferenciación tumoral. Metodología: Usando técnicas de inmunohistoquímica se determinaron los receptores de estrógeno (RE) y progesterona (RP), y la sobreexpresión de la proteína HER-2/neu en muestras de carcinoma ductal infiltrante y se identificaron sus fenotipos basados en la clasificación de Cheang. La variedad histológica y el grado de diferenciación tumoral en los carcinomas ductales infiltrantes fueron evaluados en tejido coloreado con hematoxilina-eosina. Resultados: Se incluyeron las muestras de 58 pacientes con carcinoma ductal infiltrante. El 15,5% de los carcinomas eran bien diferenciados, 63,8% moderadamente diferenciados y el 20,7% restante pobremente diferenciados. El inmunofenotipo triple negativo se presentó en 29,3% de las muestras, HER2+ en el 20,7%, luminal/ HER2+ en el 1,7%, luminal A en el 43,1% y ER-/PR+/HER2- en el 5,2%. Conclusión: En nuestro estudio, no se encontró asociación entre el grado de diferenciación tumoral y los inmunofenotipos. Salud UIS 2011; 43 (2): 149-158.

Introduction: The degree of tumor differentiation, the expression of estrogen and progesterone receptors and HER-2/ neu protein overexpressing are important prognostic and predictive factors in the evolution and therapeutic management of invasive breast carcinoma. In different studies were found that the immunophenotypes that do not express hormonal receptors or the HER-2/neu protein overexpressing have been associated with poor tumor differentiation. Purpose: To determine the immunophenotypic profile of invasive ductal carcinoma and establish its relationship with the histological grade. Methodology: Using immunohistochemistry were determined the estrogen receptor (ER) and progesterone (PR) and HER-2/neu protein overexpression in invasive ductal carcinoma samples and their phenotypes were identified based on classification of Cheang. The histological subtype and degree of tumor differentiation in invasive ductal carcinomas were evaluated in tissue stained with hematoxylin-eosin. Results: In this study were included 58 patients with invasive ductal carcinoma. 15.5% of the carcinomas were well differentiated, 63.8% moderately differentiated and the remaining 20.7% poorly differentiated. The triple-negative immunophenotype was show in 29.3% of the samples, HER2+ in the 20.7%, luminal/HER2 + in the 1.7%, luminal A in the 43.1% and the phenotype (ER-/PR+/HER2) in the 5.2%. Conclusion: In this study don't was found association between the degree of tumor differentiation and the immunophenotypes. Salud UIS 2011; 43 (2): 149-158.

Percepciones de terapeutas ocupacionales sobre el lenguaje y la comunicación de los niños con déficit de integración sensorial / Language and communication in children with sensory deficit: the occupational therapists perception

Antecedentes. Los terapeutas ocupacionales y fonoaudiólogos trabajan, con frecuencia, en equipo interdisciplinario, para que los niños con déficit de integración sensorial puedan mejorar su desempeño personal, social y escolar. Estos equipos interprofesionales desarrollan con la práctica una valiosa comprensión de las características lingüísticas y comunicativas de los niños en tratamiento. Objetivo. Describir la percepción que tienen los terapeutas ocupacionales sobre las características lingüísticas y comunicativas de los niños con déficit de integración sensorial. Material y métodos. Se realizaron entrevistas semiestructuradas a cinco terapeutas ocupacionales de Bogotá, certificadas como integradoras sensoriales, con experiencia en el manejo de niños (entre los 4 y 6 años) con diagnóstico de déficit de integración sensorial. Resultados. Los resultados muestran que los niños con déficit de integración sensorial, dependiendo del tipo de sistema sensorial afectado, se describen como niños con un lenguaje desorganizado, dificultades de habla y de escritura. Esta situación sugiere la necesidad de trabajo interdisciplinario con el fonoaudiólogo. Conclusión. Según la opinión de las terapeutas ocupacionales entrevistadas, la intervención en terapia ocupacional basada en la integración sensorial es efectiva y produce cambios positivos en el lenguaje, y no siempre es necesaria la intervención fonoaudiológica a menos que el niño muestre problemas importantes con el habla y la escritura. Estos hallazgos sugieren la necesidad de trabajo interprofesional.

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Uruguay: development of tissues quality control and quality management system in the National Multi-Tissue Bank of Uruguay.

BNOT was created and regulated in 1977 and started its operation in 1978 according to the Decree No. 86/1977. By the Decree 248/005 is transformed in the National Institute of Donation and Transplantation of Cells, Tissues and Organs (Instituto Nacional de Donación y Trasplante de Células, Tejidos y Organos--INDT). The organisation has been operating within the State University Medical School and the Public Health Secretary and it is the governmental organisation responsible for the regulation, policy and management of donation and transplantation in Uruguay. By the Decree 160/2006 is responsible for human cells and tissues regulation too. The participation of the INDT in the IAEA program facilitated the introduction of the radiation sterilisation technique for the first time in the country. The radiation sterilisation of tissues processed by INDT (ex BNOT), was initially carried out in the 60 Cobalt Industrial Plant in the National Atomic Energy Commission of Argentina and now is carried out in INDT, using a Gamma Cell 220 Excel, which was provided by the IAEA through the national project URU/7/005. The results of the implementation of tissues, quality control and quality management system, are showed.

Periodic perturbations in Shaker K+ channel gating kinetics by deletions in the S3-S4 linker.

Upon depolarization positive charges contained in the transmembrane segment S4 of voltage-dependent channels are displaced from the cytoplasmic to the external milieu. This charge movement leads to channel opening. In Shaker K+ channels four positively charged arginines in the S4 domain are transferred from the internal to the external side of the channel during activation. The distance traveled by the S4 segment during activation is unknown, but large movements should be constrained by the S3-S4 linker. Constructing deletion mutants, we show that the activation time constant and the midpoint of the voltage activation curve of the Shaker K+ channel macroscopic currents becomes a periodic function of the S3-S4 linker length for linkers shorter than 7 aa residues. The periodicity is that typical of alpha-helices. Moreover, a linker containing only 3 aa is enough to recover the wild-type phenotype. The deletion method revealed the importance of the S3-S4 linker in determining the channel gating kinetics and indicated that the alpha-helical nature of S4 extends toward its N terminus. These results support the notion that a small displacement of the S4 segment suffices to displace the four gating charges involved in channel opening.

Traumatic disruption of the pancreatic duct: diagnosis with MR pancreatography.

OBJECTIVE. We evaluated the ability of MR pancreatography to reveal traumatic disruptions of the pancreatic duct compared with retrograde pancreatography. CONCLUSION. MR pancreatography is an adequate noninvasive test for the detection of complete traumatic disruptions of the main pancreatic duct. MR pancreatography is especially useful for delineating the segments of the duct that cannot be evaluated with retrograde pancreatography.

Papel de la laparoscopia en el tratamiento del síndrome de Peutz Jeghers: revisión de la literatura / Role of laparoscopy in the treatment of Peutz Jeghers Syndrome

La enteroscopia en combinacion con la laparoscopia son un metodo seguro y efectivo en el tratamiento de los polipos en el sindrome de Peutz Jeghers, eliminando las multiples laparotomias que estos pacientes requieren y las complicaciones derivadas de ellas, más las ventajas de la cirugia videoasistida ya conocidas por todos. Se reporta nuestra experiencia con un paciente joven con diagnostico previo de sindrome de Peutz Jeghers, con cuadro de dolor abdominal asociado a sindrome anemico; se le realiza acceso combinado de laparoscopia y enteroscopia intraoperatoria videoasistida con polipectomia y reseccion de polipos. Se realiza una breve revision de la literatura y la descripcion de la tecnica operatoria.

Diagnosing bile duct stones: comparison of unenhanced helical CT, oral contrast-enhanced CT cholangiography, and MR cholangiography.

OBJECTIVE: In this investigation we compared the diagnostic performance of unenhanced helical CT, oral contrast-enhanced CT cholangiography, and MR cholangiography for the diagnosis of choledocholithiasis. SUBJECTS AND METHODS: Fifty-one patients referred for endoscopic retrograde cholangiography of suspected biliary stones were studied with unenhanced helical CT, MR cholangiography, and helical CT performed after oral administration of a cholangiographic contrast agent (iopodic acid). The studies were randomized for interpretation. Two radiologists evaluated the images by consensus and determined the presence and location of stones. We used retrograde cholangiography findings as the standard of reference. Sensitivity and specificity (with 95% confidence intervals [CIs]) of the three examinations were calculated and compared using the exact form of the McNemar test. RESULTS: Bile duct stones were revealed with retrograde cholangiography in 26 patients (51%). Sensitivity was 65% (95% CI, 44.4-82%) for unenhanced helical CT, 92% (95% CI, 73-99%) for CT cholangiography, and 96% (95% CI, 78-99%) for MR cholangiography. Specificity was 84% (95% CI, 63-95%) for unenhanced helical CT, 92% (95% CI, 73-99%) for CT cholangiography, and 100% (95% CI, 83-100%) for MR cholangiography. The sensitivity of CT cholangiography and MR cholangiography was significantly higher than that of unenhanced helical CT (p<0.01). Differences in specificity were not significant. CONCLUSION: Our results indicate that oral contrast-enhanced CT cholangiography and MR cholangiography are significantly more sensitive than unenhanced helical CT for the detection of bile duct calculi.

Detection of choledocholithiasis with MR cholangiography: comparison of three-dimensional fast spin-echo and single- and multisection half-Fourier rapid acquisition with relaxation enhancement sequences.

PURPOSE: To compare the performance of three pulse sequences commonly used at magnetic resonance (MR) cholangiography in the diagnosis of choledocholithiasis. MATERIALS AND METHODS: MR cholangiography was performed in 57 patients who were suspected of having choledocholithiasis and referred for endoscopic retrograde cholangiography. Non-breath-hold three-dimensional fast spin-echo, breath-hold single-section half-Fourier rapid acquisition with relaxation enhancement (RARE), and breath-hold multisection half-Fourier RARE sequences were compared. Two radiologists independently interpreted the MR cholangiograms. Evaluated diagnostic performance parameters included sensitivity, specificity, receiver operating characteristic (ROC) curves, and interobserver agreement (kappa statistics). Endoscopic retrograde cholangiography was the standard of reference. RESULTS: Eight patients were excluded because of incomplete MR examinations (n = 4) or failure in the cannulation of the bile duct at retrograde cholangiography (n = 4). In 49 patients, the three MR cholangiographic sequences were completed successfully. In 24 (49%) of these patients, retrograde cholangiography demonstrated stones. Sensitivity and specificity of MR cholangiography exceeded 90%, and the area under the ROC curve was greater than 0.95 for both radiologists and for the three sequences. Interobserver agreement for presence of bile duct stones was at least 0.80 (very good) for the three sequences. CONCLUSION: The three MR cholangiographic sequences had similarly high sensitivities and specificities for the detection of choledocholithiasis.

Experiencia inicial con el stent esofagico de song para el tratamiento paliativo de la disfagia maligna benigna y fistula esofagotraqueal / Initial experience with esophageal stent, song type fot palliative treatment of bening and malignat dysphagia and tracheoesophageal fistula

Se evaluaron los resultados clínicos de la colocación de stents esofágicos autoexpandibles recubiertos tipo Song de fabricación local en el tratamiento paliativo de la disfagia tumoral, por estenosis benigna y en casos de fístula esofagotraqueal. Entre Agosto de 1998 y Mayo de 1999 se colocaron 27 stents en 24 pacientes, 20 pacientes con estenosis malignas del esófago y 4 pacientes con estenosis benignas. El stent se construyó localmente con alambre de acero inoxidable en Z, cubierto de una membrana de poliuretano. Todos los pacientes presentaban disfagia severa a líquidos o comidas blandas y se consideraron inoperables o malos candidatos quirúrgicos. La colocación del stent fue técnicamente posible en 23 pacientes. En un paciente el stent migró superiormente. Dos pacientes requirieron 2 stents cada uno. Mejoría significativa de la disfagia se observó en 23 pacientes. Las complicaciones tempranas fueron dolor severo (n=3) y sangrado que requirió transfusión (n= 1). Complicaciones tardías incluyeron migración (n = 1) y obstrucción por comida (n = 1). Síntomas de reflujo gastroesofágico severo se observaron en 3 pacientes. Stents con válvulas antirreflujos se utilizaron en 4 pacientes sin presencia de reflujo significativo ni obstrucción por comida. Los stents esofágicos autoexpandibles recubiertos ofrecen una paliación efectiva de la disfagia de origen tumoral y es el tratamiento de elección en las fístulas traqueoesofágicas en pacientes que no sean candidatos quirúrgicos. En un grupo seleccionado de pacientes con estenosis esofágicas benignas, la colocación de stents en forma temporal o permanente ofrece una alternativa al manejo no quirúrgico de la disfagia

Biliary obstruction: findings at MR cholangiography and cross-sectional MR imaging.

Twenty-two patients with malignant biliary obstruction and 21 patients with suspected obstruction of biliary-enteric anastomoses were evaluated over a 12-month period with magnetic resonance (MR) cholangiography and cross-sectional MR imaging. In patients with malignant obstruction, MR cholangiography helped accurately determine the status of the biliary ductal system by identifying the exact location and extent of the obstruction and the severity of duct dilatation. In so doing, MR cholangiography helped determine whether percutaneous transhepatic cholangiography with antegrade stent placement or retrograde cholangiography with stent placement constituted the more suitable treatment. Cross-sectional MR imaging was necessary to identify the organ of tumor origin, define the tumor margins, and determine the stage of disease. This information helped evaluate the appropriateness of curative surgical therapy versus palliative drainage procedures. In patients with biliary-enteric anastomoses, MR cholangiography clearly depicted the site of the anastomosis and demonstrated the status of the intrahepatic ducts, thereby helping determine which patients would benefit from undergoing antegrade duct cannulation with a drainage procedure or perhaps balloon dilation. In some of these patients, MR cholangiography was sufficient to help plan therapeutic intervention. MR cholangiography also demonstrates the presence and size of biliary stones and associated findings such as intraductal tumor growth. In addition, MR cholangiography may obviate retrograde cholangiography, which can be technically difficult to perform.

Localization of the K+ lock-In and the Ba2+ binding sites in a voltage-gated calcium-modulated channel. Implications for survival of K+ permeability.

Using Ba2+ as a probe, we performed a detailed characterization of an external K+ binding site located in the pore of a large conductance Ca2+-activated K+ (BKCa) channel from skeletal muscle incorporated into planar lipid bilayers. Internal Ba2+ blocks BKCa channels and decreasing external K+ using a K+ chelator, (+)-18-Crown-6-tetracarboxylic acid, dramatically reduces the duration of the Ba2+-blocked events. Average Ba2+ dwell time changes from 10 s at 10 mM external K+ to 100 ms in the limit of very low [K+]. Using a model where external K+ binds to a site hindering the exit of Ba2+ toward the external side (Neyton, J., and C. Miller. 1988. J. Gen. Physiol. 92:549-568), we calculated a dissociation constant of 2.7 mircoM for K) at this lock-in site. We also found that BK(Ca) channels enter into a long-lasting nonconductive state when the external [K+] is reduced below 4 microM using the crown ether. Channel activity can be recovered by adding K+, Rb+, Cs+, or NH4+ to the external solution. These results suggest that the BK(Ca) channel stability in solutions of very low [K+] is due to K+ binding to a site having a very high affinity. Occupancy of this site by K+ avoids the channel conductance collapse and the exit of Ba2+ toward the external side. External tetraethylammonium also reduced the Ba2+ off rate and impeded the channel from entering into the long-lasting nonconductive state. This effect requires the presence of external K+. It is explained in terms of a model in which the conduction pore contains Ba2+, K+, and tetraethylammonium simultaneously, with the K+ binding site located internal to the tetraethylammonium site. Altogether, these results and the known potassium channel structure (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69-77) imply that the lock-in site and the Ba2+ sites are the external and internal ion sites of the selectivity filter, respectively.

Role of the S4 segment in a voltage-dependent calcium-sensitive potassium (hSlo) channel.

We investigated the role of individual charged residues of the S4 region of a MaxiK channel (hSlo) in channel gating. We measured macroscopic currents induced by wild type (WT) and point mutants of hSlo in inside-out membrane patches of Xenopus laevis oocytes. Of all the residues tested, only neutralizations of Arg-210 and Arg-213 were associated with a reduction in the number of gating charges as determined using the limiting slope method. Channel activation in WT and mutant channels was interpreted using an allosteric model. Mutations R207Q, R207E, and R210N facilitated channel opening in the absence of Ca2+; however, this facilitation was not observed in the channels Ca2+-bound state. Mutation R213Q behaved similarly to the WT channel in the absence of Ca2+, but Ca2+ was unable to stabilize the open state to the same extent as it does in the WT. Mutations R207Q, R207E, R210N, and R213Q reduced the coupling between Ca2+ binding and channel opening when compared with the WT. Mutations L204R, L204H, Q216R, E219Q, and E219K in the S4 domain showed a similar phenotype to the WT channel. We conclude that the S4 region in the hSlo channel is part of the voltage sensor and that only two charged amino acid residues in this region (Arg-210 and Arg-213) contribute to the gating valence of the channel.