Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
BMC Med Educ ; 23(1): 173, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36941597

RESUMEN

BACKGROUND: In medicine, critical thinking is required for managing and tolerating medical uncertainty, as well as solving professional problems and treating diseases. However, the core of Confucianism, teacher-centered and exam-oriented settings in middle and high school education may pose challenges to developing critical thinking in Han Chinese or Taiwanese students. Students may be adversely affected by these pedagogies since student-centered settings were more effective in stimulating their critical and reflective thinking, as well as a sense of responsibility, in the ever-changing world. Therefore, guiding students with less stable foundations of critical thinking might require a different approach. A review article highlighted the potential utility of the Socratic method as a tool for teaching critical thinking in the healthcare field. The method involves posing a series of questions to students. More importantly, medical students and residents in clinical teaching are familiar with the method. Almost all healthcare students must complete a biochemistry laboratory course as part of their basic science training. Thus, we aimed to train students to develop critical thinking in the biochemistry laboratory course by using learning sheets and teacher guidance based on the Socratic method and questioning. METHOD: We recruited second-year students from a medical school, of whom 32 had medical science and biotechnology majors (MSB), 27 had pharmaceutical science majors (PS), and 85 were medical undergraduate (MU) students. An exercise in critical thinking was conducted during a biochemistry laboratory course, which consisted of five different biochemical experiments, along with learning sheets that contained three or four critical thinking questions. Then, the teacher evaluated the students' ability to think critically based on nine intellectual dimensions (clarity, accuracy, precision, relevance, depth, breadth, logic, fairness, and significance) based on the universal intellectual standards developed by Prof. Linda Elder and Richard Paul. In the following analysis, regression models and multivariate analysis were used to determine how students improved over time, and trajectory analysis were carried out in order to observe the trends in students' critical thinking skills construction. RESULTS: Clarity and logic dimensions were identified as the key elements to facilitate the development of critical thinking skills through learning sheets and teacher guidance in students across all three different healthcare majors. The results showed that metacognitive monitoring via Socratic questioning learning sheets have demonstrated potential encourage students to develop critical thinking skills in all dimensions. Another unique contribution of current study was present the heterogeneous learning patterns and progress trajectories of clarity and logic dimensions within classes. CONCLUSION: Using the Socratic learning model could effectively develop students' critical thinking skills so they can more effectively care for their patients.


Asunto(s)
Bachillerato en Enfermería , Estudiantes de Medicina , Humanos , Anciano , Pensamiento , Solución de Problemas , Bachillerato en Enfermería/métodos , Atención a la Salud
2.
Healthc Technol Lett ; 5(1): 38-44, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29515815

RESUMEN

Blood leakage and blood loss are serious life-threatening complications occurring during dialysis therapy. These events have been of concerns to both healthcare givers and patients. More than 40% of adult blood volume can be lost in just a few minutes, resulting in morbidities and mortality. The authors intend to propose the design of a warning tool for the detection of blood leakage/blood loss during dialysis therapy based on fog computing with an array of photocell sensors and heteroassociative memory (HAM) model. Photocell sensors are arranged in an array on a flexible substrate to detect blood leakage via the resistance changes with illumination in the visible spectrum of 500-700 nm. The HAM model is implemented to design a virtual alarm unit using electricity changes in an embedded system. The proposed warning tool can indicate the risk level in both end-sensing units and remote monitor devices via a wireless network and fog/cloud computing. The animal experimental results (pig blood) will demonstrate the feasibility.

3.
J Appl Physiol (1985) ; 124(4): 899-905, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29357510

RESUMEN

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8-15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1ß, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Benzaldehídos/uso terapéutico , Niacinamida/análogos & derivados , Lesión Pulmonar Aguda/etiología , Animales , Benzaldehídos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Lipopolisacáridos , Masculino , Ratones Endogámicos C57BL , Niacinamida/farmacología , Niacinamida/uso terapéutico
4.
Oncotarget ; 8(61): 104007-104021, 2017 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-29262617

RESUMEN

Microtubule targeting drugs like taxanes, vinca alkaloids, and epothilones are widely-used and effective chemotherapeutic agents that target the dynamic instability of microtubules and inhibit spindle functioning. However, these drugs have limitations associated with their production, solubility, efficacy and unwanted toxicities, thus driving the need to identify novel antimitotic drugs that can be used as anticancer agents. We have discovered and characterized the Microtubins (Microtubule inhibitors), a novel class of small synthetic compounds, which target tubulin to inhibit microtubule polymerization, arrest cancer cells predominantly in mitosis, activate the spindle assembly checkpoint and trigger an apoptotic cell death. Importantly, the Microtubins do not compete for the known vinca or colchicine binding sites. Additionally, through chemical synthesis and structure-activity relationship studies, we have determined that specific modifications to the Microtubin phenyl ring can activate or inhibit its bioactivity. Combined, these data define the Microtubins as a novel class of compounds that inhibit cancer cell proliferation by perturbing microtubule polymerization and they could be used to develop novel cancer therapeutics.

5.
IEEE Trans Biomed Circuits Syst ; 11(4): 784-793, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28727557

RESUMEN

Blood leakage and blood loss are serious complications during hemodialysis. From the hemodialysis survey reports, these life-threatening events occur to attract nephrology nurses and patients themselves. When the venous needle and blood line are disconnected, it takes only a few minutes for an adult patient to lose over 40% of his / her blood, which is a sufficient amount of blood loss to cause the patient to die. Therefore, we propose integrating a flexible sensor and self-organizing algorithm to design a cloud computing-based warning device for blood leakage detection. The flexible sensor is fabricated via a screen-printing technique using metallic materials on a soft substrate in an array configuration. The self-organizing algorithm constructs a virtual direct current grid-based alarm unit in an embedded system. This warning device is employed to identify blood leakage levels via a wireless network and cloud computing. It has been validated experimentally, and the experimental results suggest specifications for its commercial designs. The proposed model can also be implemented in an embedded system.


Asunto(s)
Nube Computacional , Hemorragia/diagnóstico , Monitoreo Fisiológico/instrumentación , Diálisis Renal , Tecnología Inalámbrica , Algoritmos , Sistemas de Computación , Humanos
6.
IET Syst Biol ; 11(2): 69-76, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28476975

RESUMEN

Atherosclerosis and resultant peripheral arterial disease (PAD) are common complications in patients with type 2 diabetes mellitus or end-stage renal disease and in elderly patients. The prevalence of PAD is higher in patients receiving haemodialysis therapy. For early assessment of arterial occlusion using bilateral photoplethysmography (PPG), such as changes in pulse transit time and pulse shape, bilateral timing differences could be used to identify the risk level of PAD. Hence, the authors propose a discrete fractional-order integrator to calculate the bilateral area under the systolic peak (AUSP). These indices indicated the differences in both rise-timing and amplitudes of PPG signals. The dexter and sinister AUSP ratios were preliminarily used to separate the normal condition from low/high risk of PAD. Then, transition probability-based decision-making model was employed to evaluate the risk levels. The joint probability could be specified as a critical threshold, < 0.81, to identify the true positive for screening low or high risk level of PAD, referring to the patients' health records. In contrast to the bilateral timing differences and traditional methods, the proposed model showed better efficiency in PAD assessments and provided a promising strategy to be implemented in an embedded system.


Asunto(s)
Técnicas de Apoyo para la Decisión , Técnicas de Diagnóstico Cardiovascular , Modelos Estadísticos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/etiología , Fotopletismografía , Diálisis Renal/efectos adversos , Algoritmos , Simulación por Computador , Toma de Decisiones Asistida por Computador , Técnicas de Diagnóstico Cardiovascular/instrumentación , Estudios de Factibilidad , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
7.
Physiol Rep ; 4(17)2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27624688

RESUMEN

Although exertional dyspnea and worsening hypoxia are hallmark clinical features of idiopathic pulmonary fibrosis (IPF), no drug currently available could treat them. GBT1118 is a novel orally bioavailable small molecule that binds to hemoglobin and produces a concentration-dependent left shift of the oxygen-hemoglobin dissociation curve with subsequent increase in hemoglobin-oxygen affinity and arterial oxygen loading. To assess whether pharmacological modification of hemoglobin-oxygen affinity could ameliorate hypoxemia associated with lung fibrosis, we evaluated GBT1118 in a bleomycin-induced mouse model of hypoxemia and fibrosis. After pulmonary fibrosis and hypoxemia were induced, GBT1118 was administered for eight consecutive days. Hypoxemia was determined by monitoring arterial oxygen saturation, while the severity of pulmonary fibrosis was assessed by histopathological evaluation and determination of collagen and leukocyte levels in bronchoalveolar lavage fluid. We found that hemoglobin modification by GBT1118 had strong antihypoxemic therapeutic effects with improved arterial oxygen saturation to near normal level. Moreover, GBT1118 treatment significantly attenuated bleomycin-induced lung fibrosis, collagen accumulation, body weight loss, and leukocyte infiltration. This study is the first to suggest the beneficial effects of hemoglobin modification in fibrotic lungs and offers a promising and novel therapeutic strategy for the treatment of hypoxemia associated with chronic fibrotic lung disorders in human, including IPF.


Asunto(s)
Benzaldehídos/administración & dosificación , Bleomicina/administración & dosificación , Hipoxia/inducido químicamente , Fibrosis Pulmonar Idiopática/inducido químicamente , Niacinamida/análogos & derivados , Oxígeno/metabolismo , Oxihemoglobinas/efectos de los fármacos , Administración Oral , Animales , Benzaldehídos/metabolismo , Benzaldehídos/farmacocinética , Benzaldehídos/farmacología , Bleomicina/efectos adversos , Bleomicina/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Disnea/diagnóstico , Disnea/etiología , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Niacinamida/administración & dosificación , Niacinamida/metabolismo , Niacinamida/farmacocinética , Niacinamida/farmacología , Oxígeno/sangre , Oxihemoglobinas/metabolismo , Distribución Aleatoria
8.
Healthc Technol Lett ; 3(4): 290-296, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30800319

RESUMEN

Blood leakages and blood loss are both serious complications during dialysis therapies. According to dialysis survey reports, these events are life-threatening issues for nephrology nurses, medical staff, and patients. When venous needle dislodgement occurs, it takes only <2.5 min of reaction time for blood loss in an adult patient, resulting in mortality. As an early-warning design, a wireless assistive technology using an integrated flexible sensor and virtual alarm unit was developed to detect blood leakage during dialysis therapies. The flexible sensor was designed using a screen print technique with printing electronic circuits on a plastic substrate. A self-organising algorithm was used to design a virtual alarm unit, consisting of a virtual direct current grid and a virtual alarm driver. In other words, this warning device was employed to identify the blood leakage levels via wireless fidelity wireless network in cloud computing. The feasibility was verified, and commercialisation designs can also be implemented in an embedded system.

9.
Healthc Technol Lett ; 2(3): 64-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26609407

RESUMEN

The bilateral photoplethysmography (PPG) analysis for arteriovenous fistula (AVF) dysfunction screening with a fractional-order feature and a cooperative game (CG)-based embedded detector is proposed. The proposed detector uses a feature extraction method and a CG to evaluate the risk level for AVF dysfunction for patients undergoing haemodialysis treatment. A Sprott system is used to design a self-synchronisation error formulation to quantify the differences in the changes of blood volume for the sinister and dexter thumbs' PPG signals. Bilateral PPGs exhibit a significant difference in rise time and amplitude, which is proportional to the degree of stenosis. A less parameterised CG model is then used to evaluate the risk level. The proposed detector is also studied using an embedded system and bilateral optical measurements. The experimental results show that the risk of AVF stenosis during haemodialysis treatment is detected earlier.

10.
ScientificWorldJournal ; 2015: 697569, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26171419

RESUMEN

This study proposes virtual-reality (VR) simulator system for double interventional cardiac catheterization (ICC) using fractional-order vascular access tracker and haptic force producer. An endoscope or a catheter for diagnosis and surgery of cardiovascular disease has been commonly used in minimally invasive surgery. It needs specific skills and experiences for young surgeons or postgraduate year (PGY) students to operate a Berman catheter and a pigtail catheter in the inside of the human body and requires avoiding damaging vessels. To improve the training in inserting catheters, a double-catheter mechanism is designed for the ICC procedures. A fractional-order vascular access tracker is used to trace the senior surgeons' consoled trajectories and transmit the frictional feedback and visual feedback during the insertion of catheters. Based on the clinical feeling through the aortic arch, vein into the ventricle, or tortuous blood vessels, haptic force producer is used to mock the elasticity of the vessel wall using voice coil motors (VCMs). The VR establishment with surgeons' consoled vessel trajectories and hand feeling is achieved, and the experimental results show the effectiveness for the double ICC procedures.


Asunto(s)
Cateterismo Cardíaco , Catéteres Cardíacos , Simulación por Computador , Interfaz Usuario-Computador , Algoritmos , Angiografía , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/métodos , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/cirugía , Humanos , Procesamiento de Imagen Asistido por Computador , Procedimientos Quirúrgicos Mínimamente Invasivos , Reproducibilidad de los Resultados
11.
J Exp Med ; 212(7): 1011-20, 2015 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-26077720

RESUMEN

Regulatory T cell (T reg cell) numbers and activities are tightly calibrated to maintain immune homeostasis, but the mechanisms involved are incompletely defined. Here, we report that the lysophosphatidylserine (LysoPS) receptor GPR174 is abundantly expressed in developing and mature T reg cells. In mice that lacked this X-linked gene, T reg cell generation in the thymus was intrinsically favored, and a higher fraction of peripheral T reg cells expressed CD103. LysoPS could act in vitro via GPR174 to suppress T cell proliferation and T reg cell generation. In vivo, LysoPS was detected in lymphoid organ and spinal cord tissues and was abundant in the colon. Gpr174(-/Y) mice were less susceptible to experimental autoimmune encephalomyelitis than wild-type mice, and GPR174 deficiency in T reg cells contributed to this phenotype. This study provides evidence that a bioactive lipid, LysoPS, negatively influences T reg cell accumulation and activity through GPR174. As such, GPR174 antagonists might have therapeutic potential for promoting immune regulation in the context of autoimmune disease.


Asunto(s)
Homeostasis/inmunología , Lisofosfolípidos/metabolismo , Receptores Acoplados a Proteínas G/inmunología , Receptores Lisofosfolípidos/inmunología , Linfocitos T Reguladores/inmunología , Animales , Antígenos CD/metabolismo , Proliferación Celular , Cromatografía Liquida , Colon/metabolismo , Cartilla de ADN , Citometría de Flujo , Cadenas alfa de Integrinas/metabolismo , Tejido Linfoide/metabolismo , Ratones , Receptores Acoplados a Proteínas G/metabolismo , Receptores Lisofosfolípidos/metabolismo , Médula Espinal/metabolismo , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/metabolismo , Espectrometría de Masas en Tándem
12.
PLoS Comput Biol ; 11(3): e1004153, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25826798

RESUMEN

Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60-70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/).


Asunto(s)
Biología Computacional/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Algoritmos , Sitios de Unión , Bases de Datos Factuales , Diseño de Fármacos , Humanos , Ligandos
13.
Materials (Basel) ; 8(12): 8392-8413, 2015 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-28793718

RESUMEN

The biomechanical properties of soft tissues vary with pathological phenomenon. Ultrasound elasticity imaging is a noninvasive method used to analyze the local biomechanical properties of soft tissues in clinical diagnosis. However, the echo signal-to-noise ratio (eSNR) is diminished because of the attenuation of ultrasonic energy by soft tissues. Therefore, to improve the quality of elastography, the eSNR and depth of ultrasound penetration must be increased using chirp-coded excitation. Moreover, the low axial resolution of ultrasound images generated by a chirp-coded pulse must be increased using an appropriate compression filter. The main aim of this study is to develop an ultrasound elasticity imaging system with chirp-coded excitation using a Tukey window for assessing the biomechanical properties of soft tissues. In this study, we propose an ultrasound elasticity imaging system equipped with a 7.5-MHz single-element transducer and polymethylpentene compression plate to measure strains in soft tissues. Soft tissue strains were analyzed using cross correlation (CC) and absolution difference (AD) algorithms. The optimal parameters of CC and AD algorithms used for the ultrasound elasticity imaging system with chirp-coded excitation were determined by measuring the elastographic signal-to-noise ratio (SNRe) of a homogeneous phantom. Moreover, chirp-coded excitation and short pulse excitation were used to measure the elasticity properties of the phantom. The elastographic qualities of the tissue-mimicking phantom were assessed in terms of Young's modulus and elastographic contrast-to-noise ratio (CNRe). The results show that the developed ultrasound elasticity imaging system with chirp-coded excitation modulated by a Tukey window can acquire accurate, high-quality elastography images.

14.
Chem Res Toxicol ; 28(1): 43-50, 2015 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-25486454

RESUMEN

Acrylamide (AA), a rodent carcinogen, is widely used in industry and present in cigarette smoke as well as in foods processed at high temperatures. The metabolic activation of AA to glycidamide (GA) could be critical for AA carcinogenicity since GA causes DNA adduct formation in vivo. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct of AA, is subjected to spontaneous and enzymatic depurination and excreted through urine. Urinary N7-GAG analysis can confirm AA genotoxicity and identify active species of AA metabolites in humans, thereby serving as a risk-associated biomarker for molecular epidemiology studies. This study aimed to develop an isotope-dilution solid-phase extraction liquid chromatography tandem mass spectrometry method to comparatively analyze urinary N7-GAG levels in nonsmokers and smokers. Urinary N-acetyl-S-(propionamide)-cysteine (AAMA), a metabolite of AA, was also analyzed as a biomarker for current AA exposure. Urinary N7-GAG was quantified by monitoring m/z 239 → 152 for N7-GAG and m/z 242 → 152 for (13)C3-labeled N7-GAG under positive electron spray ionization and multiple reaction mode. The median urinary N7-GAG level was 0.93 µg/g creatinine in nonsmokers (n = 33) and 1.41 µg/g creatinine in smokers (n = 30). Multiple linear regression analysis of data revealed that N7-GAG levels were only significantly associated with AAMA levels. These results demonstrate that urinary N7-GAG of nonsmokers and smokers is significantly associated with a very low level of dietary AA intake, assessed by analyzing urinary AAMA.


Asunto(s)
Acetilcisteína/análogos & derivados , Acrilamida/metabolismo , Carcinógenos/metabolismo , Cotinina/orina , Guanina/análogos & derivados , Fumar/orina , Acetilcisteína/orina , Adulto , Biomarcadores/orina , Dieta , Exposición a Riesgos Ambientales/análisis , Guanina/orina , Humanos , Adulto Joven
15.
J Med Chem ; 57(17): 7355-66, 2014 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-25122533

RESUMEN

To block the metabolically labile sites of novel tubulin inhibitors targeting the colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, and biologically tested three focused sets of new derivatives with modifications at the carbonyl linker, the para-position in the C ring of SMART template, and modification of A ring of the PAT template. Structure-activity relationships of these compounds led to the identification of new benzimidazole and imidazo[4,5-c]pyridine-fused ring templates, represented by compounds 4 and 7, respectively, which showed enhanced antitumor activity and substantially improved the metabolic stability in liver microsomes compared to SMART. MOM group replaced TMP C ring and generated a potent analogue 15, which showed comparable potency to the parent SMART compound. Further modification of PAT template yielded another potent analogue 33 with 5-indolyl substituent at A ring.


Asunto(s)
Antineoplásicos/farmacología , Colchicina/química , Moduladores de Tubulina/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colchicina/metabolismo , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Químicos , Modelos Moleculares , Estructura Molecular , Unión Proteica , Estructura Terciaria de Proteína , Relación Estructura-Actividad , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/metabolismo
16.
ScientificWorldJournal ; 2014: 203148, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24892039

RESUMEN

This study proposes multiple-site hemodynamic analysis of Doppler ultrasound with an adaptive color relation classifier for arteriovenous access occlusion evaluation in routine examinations. The hemodynamic analysis is used to express the properties of blood flow through a vital access or a tube, using dimensionless numbers. An acoustic measurement is carried out to detect the peak-systolic and peak-diastolic velocities of blood flow from the arterial anastomosis sites (A) to the venous anastomosis sites (V). The ratio of the supracritical Reynolds (Re(supra)) number and the resistive (Res) index quantitates the degrees of stenosis (DOS) at multiple measurement sites. Then, an adaptive color relation classifier is designed as a nonlinear estimate model to survey the occlusion level in monthly examinations. For 30 long-term follow-up patients, the experimental results show the proposed screening model efficiently evaluates access occlusion.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Hemodinámica , Ultrasonografía Doppler en Color , Humanos , Diálisis Renal
17.
Clin Nephrol ; 81(5): 359-62, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-23110773

RESUMEN

A 68-year-old man presented with a spontaneous bilateral perirenal hemorrhage following a 2-month fever of unknown origin. A renal biopsy for a pathologic diagnosis seemed very risky because of the patient's bilateral perirenal hemorrhage. Therefore, we diagnosed polyarteritis nodosa using an abdominal computed tomography scan, a renal angiogram, and American College of Rheumatology criteria. The patient's multiple symptoms then responded well to the prescribed immunosuppressive regimen. This case is an uncommon presentation of polyarteritis nodosa with fever of unknown origin before a spontaneous bilateral perirenal hemorrhage.


Asunto(s)
Fiebre de Origen Desconocido/complicaciones , Hemorragia/etiología , Poliarteritis Nudosa/complicaciones , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/análisis , Humanos , Masculino , Tomografía Computarizada por Rayos X
18.
Diagn Microbiol Infect Dis ; 77(3): 254-7, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24029433

RESUMEN

Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial pathogens, commonly causing catheter-related urinary tract infections or vascular catheter-related bloodstream infections. In this study, 10 Enterococcus faecium and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome-type VR clinical isolates were detected. The potential role of fosfomycin-based combination regimens for biofilm-related VRE infection is in vitro evaluated. Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline, rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based combinations were studied by time-kill method and a biofilm model. Of the fosfomycin-based combinations, a synergistic effect was particularly noted for teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin-based combinations, excluding rifampicin (40%), failed to enhance antibacterial activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%), or teicoplanin (44%). However, an antagonistic effect was found for ampicillin plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial activities of the drugs tested against VRE in vitro varied by species. Ampicillin exhibited potential activity against planktonic- and biofilm-embedded VR E. faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects against VRE even in the biofilm model, and this observation warrants further clinical studies.


Asunto(s)
Antibacterianos/farmacología , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Fosfomicina/farmacología , Resistencia a la Vancomicina , Sinergismo Farmacológico , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos
19.
Int J Cancer ; 132(6): 1475-85, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-22915089

RESUMEN

We investigated the in vitro metabolism and estrogenic and antiestrogenic activity of toremifene (TOR), tamoxifen (TAM) and their metabolites to better understand the potential effects of cytochrome P-450 2D6 (CYP2D6) status on the activity of these drugs in women with breast cancer. The plasma concentrations of TOR and its N-desmethyl (NDM) and 4-hydroxy (4-OH) metabolites during steady-state dosing with TOR were also determined. Unlike TOR, TAM and its NDM metabolite were extensively oxidized to 4-OH TAM and 4-OH-NDM TAM by CYP2D6, and the rate of metabolism was affected by CYP2D6 status. 4-OH-NDM TOR concentrations were not measurable at steady state in plasma of subjects taking 80 mg of TOR. Molecular modeling provided insight into the lack of 4-hydroxylation of TOR by CYP2D6. The 4-OH and 4-OH-NDM metabolites of TOR and TAM bound to estrogen receptor (ER) subtypes with fourfold to 30-fold greater affinity were 35- to 187-fold more efficient at antagonizing ER transactivation and had antiestrogenic potency that was up to 360-fold greater than their parent drugs. Our findings suggest that variations in CYP2D6 metabolic capacity may cause significant differences in plasma concentrations of active TAM metabolites (i.e., 4-OH TAM and 4-OH-NDM TAM) and contribute to variable pharmacologic activity. Unlike TAM, the clinical benefits in subjects taking TOR to treat metastatic breast cancer would not likely be subject to allelic variation in CYP2D6 status or affected by coadministration of CYP2D6-inhibiting medications.


Asunto(s)
Citocromo P-450 CYP2D6/fisiología , Moduladores Selectivos de los Receptores de Estrógeno/metabolismo , Tamoxifeno/metabolismo , Toremifeno/metabolismo , Adulto , Humanos , Masculino , Oxidación-Reducción , Relación Estructura-Actividad , Tamoxifeno/análogos & derivados , Tamoxifeno/sangre
20.
Med Microbiol Immunol ; 202(2): 105-15, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22797522

RESUMEN

Group B streptococcus (GBS) is a common asymptomatic colonizer in acidic vagina of pregnant women and can transmit to newborns, causing neonatal pneumonia and meningitis. Biofilm formation is often associated with bacterial colonization and pathogenesis. Little is known about GBS biofilm and the effect of environmental stimuli on their growth along with biofilm formation. The objective of this study was to investigate the survival and biofilm formation of GBS, isolated from pregnant women, in nutrient-limited medium under various pH conditions. Growth and survival experiments were determined by optical density and viable counts. Crystal violet staining, scanning electron microscopy, and atomic force microscopy (AFM) were used to analyze the capacity of biofilm production. Our results showed that GBS isolates proliferated with increasing pH with highest maximum specific growth rate (µmax) at pH 6.5, but survived at pH 4.5 for longer than 48 h. Biofilm formation of the 80 GBS isolates at pH 4.5 was significantly higher than at pH 7.0. This difference was confirmed by two other methods. The low elastic modulus obtained from samples at pH 4.5 by AFM revealed the softness of biofilm; in contrast, little or no biofilm was measured at pH 7.0. Under acidic pH, the capability of biofilm formation of serotypes III and V showed statistically significant difference from serotypes Ia and Ib. Our finding suggested that survival and enhanced biofilm formation at vaginal pH are potentially advantageous for GBS in colonizing vagina and increase the risk of vaginosis and neonatal infection.


Asunto(s)
Biopelículas , Streptococcus agalactiae/fisiología , Vagina/microbiología , Adulto , Femenino , Perfilación de la Expresión Génica , Humanos , Concentración de Iones de Hidrógeno , Embarazo , Estudios Prospectivos , Serotipificación , Streptococcus agalactiae/aislamiento & purificación , Streptococcus agalactiae/ultraestructura
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...