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1.
Behav Modif ; 46(1): 36-62, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-32752883

RESUMEN

Exposure therapy works through inhibitory learning, whereby patients are exposed to stimuli that elicit anxiety in order to establish safety associations. Mindful emotion awareness, or nonjudgmental and present-focused attention toward emotions, may facilitate engagement in exposures, which may in turn enhance therapeutic outcome. This study utilizes a single-case experimental design (n = 6) to investigate the effect of mindful emotion awareness training on the use of avoidant strategies during exposures, distress during exposures, overall mindfulness, experiential avoidance, and symptom reduction in a sample of participants with social anxiety disorder. Data were analyzed using a combination of visual inspection and quantitative effect size metrics commonly applied in single-case experimental designs. To further investigate the relationship between distress and avoidant strategy use, contemporaneous and cross-lagged correlations were run. Results highlight individual differences in responses to mindful emotion awareness training and exposure exercises. Given these individual differences, repeated assessment and monitoring over the course of treatment may help clinicians most effectively identify treatment skills that will be most helpful for individual patients.


Asunto(s)
Terapia Implosiva , Atención Plena , Trastornos de Ansiedad/psicología , Concienciación/fisiología , Emociones/fisiología , Humanos , Atención Plena/métodos , Proyectos de Investigación
2.
Behav Ther ; 52(6): 1325-1338, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34656189

RESUMEN

The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders is an emotion-focused, cognitive-behavioral intervention developed to address the full range of anxiety, depressive, and related disorders. The UP consists of core therapeutic skills that, though unique in focus, are each designed to promote an approach-oriented stance toward emotional experiences. The goal of the present investigation was to characterize changes in these skills for patients that received a course of treatment with the UP, as well as to examine associations between skills and symptoms changes. Patients with principal anxiety disorders, assigned to receive treatment with the UP (N = 88) as part of a randomized controlled trial, were included in this study. They completed validated self-report measures of UP skills (Understanding Emotions, Mindful Emotion Awareness, Cognitive Flexibility, Countering Emotional Behaviors, and Interoceptive Awareness and Tolerance), as well as clinician-rated measures of psychological symptoms. Skill measures improved significantly over the course of 12 to 16 UP treatment sessions and changes in these skills measures were associated with improvements in anxiety symptoms. Determining whether improvement on all the skills learned during a course of treatment with UP is associated with symptom remission is critical to establishing the most streamlined and efficient interventions that may ultimately be best suited to widespread dissemination.


Asunto(s)
Terapia Cognitivo-Conductual , Atención Plena , Ansiedad/terapia , Trastornos de Ansiedad/terapia , Emociones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
3.
Behav Ther ; 51(6): 933-945, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33051035

RESUMEN

Dysregulated anger in the context of emotional (e.g., mood, anxiety, related) disorders is associated with treatment attrition and a lower likelihood of responding to extant treatments. Therefore, there is a need to identify the most effective skills for targeting this anger and prioritize their delivery in treatment with the hope of producing more potent interventions. The current study explored the specific effects of two treatment skills (mindfulness and countering emotional behaviors) in isolation and combination as interventions for dysregulated anger using single-case experimental design. Patients were randomized to a 2- or 4-week baseline with no intervention applied and then to the first treatment skill received. All patients subsequently completed the alternate treatment skill and 1 month of follow-up. Results suggested the first module had clinically meaningful effects for five patients and the second module produced incremental improvement for five patients. Visual inspection and effect sizes indicated mindfulness produced greater reductions in anger when delivered in isolation compared to countering emotional behaviors (d = 0.96, 0.33, for mindfulness and countering emotional behaviors, respectively). With regard to the second module, more patients (n = 4) experienced a reduction in anger in response to mindfulness than to countering emotional behaviors (n = 1); effect sizes indicated significant improvements in response to both modules (d = 0.83, 0.72, for mindfulness and countering emotional behaviors, respectively). Taken together, results suggest mindfulness may be a more efficacious intervention for anger than countering emotional behaviors. Implications of these results for addressing dysregulated anger in treatment are discussed.


Asunto(s)
Ira , Trastornos de Ansiedad , Emociones , Atención Plena , Ansiedad , Trastornos de Ansiedad/terapia , Humanos
4.
Behav Ther ; 51(6): 972-983, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33051038

RESUMEN

The Unified Protocol for Transdiagnostic Treatment (UP; Barlow et al., 2011) has recently demonstrated statistically equivalent therapeutic effects compared to leading cognitive behavioral therapy (CBT) protocols for anxiety disorders designed to address disorder-specific symptoms (i.e., single-disorder protocols [SDP]); Barlow et al., 2017). Although all treatment protocols included similar evidence-based CBT elements, investigation of those related to symptom improvement in the UP is warranted. Because the UP is unique from the SDPs for its inclusion of mindfulness, the present study evaluated mindfulness as a primary treatment element. We explored whether UP participants, compared to SDP, demonstrated greater improvements in mindfulness from pre- to posttreatment, and whether these improvements predicted posttreatment severity across anxiety disorder diagnoses. Participants were individuals with a principle anxiety disorder (N = 179) randomized to receive either the UP or SDP. Results indicated significant improvements pre- to posttreatment in mindfulness for participants receiving either the UP or SDP. However, at posttreatment, mindfulness scores were significantly greater for the UP condition. At the diagnosis level, posttreatment scores in mindfulness were significantly greater in the UP condition than the respective SDP conditions for principal Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SOC). Moreover, results suggest that change in mindfulness is related to posttreatment severity, when moderated by treatment condition, but only for participants with principal GAD. Taken together, the UP is effective in improving mindfulness in a sample with heterogeneous anxiety disorders, but this change seems particularly relevant for reduction in symptom severity for individuals with principal GAD.


Asunto(s)
Trastornos de Ansiedad , Terapia Cognitivo-Conductual , Atención Plena , Fobia Social , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/terapia , Humanos , Resultado del Tratamiento
5.
Behav Ther ; 47(2): 225-38, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26956654

RESUMEN

The present study explored whether distress reduction in response to strong negative emotions, a putative transdiagnostic mechanism of action, is facilitated by mindfulness strategies. Seven patients (mean age=31.14years, SD=12.28, range 19-48 years, 43% female, 86% Caucasian) with heterogeneous anxiety disorders (i.e., panic disorder with or without agoraphobia, social anxiety, generalized anxiety) were assigned a randomized order of weeklong blocks utilizing either mindfulness- or avoidance-based strategies while ascending a 6-week emotion exposure hierarchy. Participants completed three exposures per block and provided distress and avoidance use ratings following each exposure. Anxiety severity, distress aversion, and distraction/suppression tendencies were also assessed at baseline and the conclusion of each block. Visual, descriptive, and effect size results showing exposures utilizing mindfulness were associated with higher overall distress levels, compared with those utilizing avoidance. Within blocks, the majority of participants exhibited declining distress levels when employing mindfulness strategies, as opposed to more static distress levels in the avoidance condition. Systematic changes in anxiety severity, distress aversion, and distraction/suppression were not observed. These results suggest mindfulness strategies may be effective in facilitating emotion exposure; however, a minimum dosage may be necessary to overcome initial distress elevation. Potential transdiagnostic change mechanisms and clinical implications are discussed.


Asunto(s)
Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Adulto , Ansiedad/psicología , Emociones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Plena , Resultado del Tratamiento , Adulto Joven
6.
J Consult Clin Psychol ; 82(6): 1060-71, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25045911

RESUMEN

UNLABELLED: Idiographic research methods can provide rich information regarding the process of change in specific treatments. OBJECTIVE: Adopting an idiographic, exploratory approach, this study examined (a) temporal patterns of 3 transdiagnostic change constructs (mindfulness, cognitive reappraisal, and emotion avoidance), (b) the relationships between these constructs and depression and anxiety symptom severity over time, and (c) changes in these constructs in relation to the introduction of specific transdiagnostic intervention strategies in a single case. METHOD: The case was a 64-year-old, White, female patient with principal major depressive disorder and secondary generalized anxiety disorder being treated with the Unified Protocol (UP). Univariate and multivariate time series analyses were applied to symptom and change construct data. RESULTS: (a) Clinically significant decreases in depression and anxiety from baseline to posttreatment were observed, as well as clinically significant increases in mindfulness and reappraisal; (b) changes in mindfulness were associated with changes in depression and anxiety, and changes in mindfulness temporally preceded changes in depression and anxiety; (c) changes in reappraisal were associated with changes in depression, and changes in reappraisal temporally preceded changes in depression; (d) the UP module designed to increase present-focused emotion awareness exerted the strongest influence on mindfulness ratings, although other modules had an impact; (e) reappraisal ratings were most strongly influenced by the emotion monitoring and functional analysis module, although subsequent modules continued to have a measureable impact. CONCLUSIONS: Although specific to this case, these results begin to elucidate important processes of change in transdiagnostic cognitive-behavioral therapy for principal depression with comorbid anxiety.


Asunto(s)
Terapia Cognitivo-Conductual , Depresión/psicología , Depresión/terapia , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Atención Plena , Ansiedad/psicología , Ansiedad/terapia , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Concienciación , Terapia Cognitivo-Conductual/métodos , Comorbilidad , Depresión/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Emociones , Femenino , Humanos , Persona de Mediana Edad
7.
Mol Pharm ; 10(12): 4408-17, 2013 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-24171434

RESUMEN

Phospholipid vesicles (liposomes) formed in pharmaceutically acceptable nonaqueous polar solvents such as propylene glycol are of interest in drug delivery because of their ability to improve the bioavailability of drugs with poor aqueous solubility. We have demonstrated a stabilizing effect of cholesterol on lamellar phases formed by dispersion of distearoylphosphatidylcholine (DSPC) in water/propylene glycol (PG) solutions with glycol concentrations ranging from 0 to 100%. The stability of the dispersions was assessed by determining the effect of propylene glycol concentration on structural parameters of the lamellar phases using a complementary combination of X-ray and neutron scattering techniques at 25 °C and in the case of X-ray scattering at 65 °C. Significantly, although stable lamellar phases (and liposomes) were formed in all PG solutions at 25 °C, the association of the glycol with the liposomes' lamellar structures led to the formation of interdigitated phases, which were not thermostable at 65 °C. With the addition of equimolar quantities of cholesterol to the dispersions of DSPC, stable lamellar dispersions (and indeed liposomes) were formed in all propylene glycol solutions at 25 °C, with the significant lateral phase separation of the bilayer components only detectable in propylene glycol concentrations above 60% (w/w). We propose that the stability of lamellar phases of the cholesterol-containing liposomes formed in propylene glycol concentrations of up to 60% (w/w) represent potentially very valuable drug delivery vehicles for a variety of routes of administration.


Asunto(s)
Colesterol/química , Fosfatidilcolinas/química , Propilenglicol/química , Sistemas de Liberación de Medicamentos/métodos , Estabilidad de Medicamentos , Glicoles/química , Liposomas/química , Soluciones/química , Temperatura , Agua/química , Difracción de Rayos X/métodos
8.
Complement Ther Med ; 21(5): 529-34, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24050592

RESUMEN

Ambulatory knee surgery is a common procedure with over 100,000 knee arthroscopies performed in the U.K. in 2010-2011. Pain after surgery can decrease patient satisfaction, delay discharge, and decrease cost effectiveness. Multi-modal therapies, including complementary therapies, to improve pain control after surgery have been recommended. However, a comprehensive review of the literature regarding the use of complementary therapies to enhance pain control after ambulatory knee surgery is lacking, and this article aims to address this deficit. CINHAL, EMBASE, MEDLINE, AMED and CENTRAL databases were searched. Only Randomised Controlled Trials were included. All eligible papers were quality assessed using the Jadad system, and data was extracted using piloted forms. Two independent reviewers performed each stage of the review. Full details of the study methodology can be found on Prospero, a systematic review register. Five studies satisfied our eligibility criteria: three reporting on acupuncture, one on homeopathy, and one on acupoints. Acupoint pressure was the only study that demonstrated reduced pain compared with placebo. This study was the least methodologically robust. Arnica, although demonstrating a significant reduction in swelling, did not affect post-operative pain. Acupuncture did not affect post-operative pain; however, a reduction in ibuprofen use was demonstrated in two studies. Before recommending complementary therapy for routine use in ambulatory knee surgery, further work is required. Two areas of future research likely to bear fruit are demonstrating robust evidence for the effect of acupoint pressure on post-operative pain, and quantifying the positive effect of homeopathic arnica on post-operative swelling.


Asunto(s)
Terapia por Acupuntura , Homeopatía , Articulación de la Rodilla/cirugía , Manejo del Dolor/métodos , Dolor Postoperatorio/terapia , Ensayos Clínicos como Asunto , Humanos
9.
Behav Res Ther ; 51(11): 729-35, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24055681

RESUMEN

The effects of the antidepressant venlafaxine (VEN-225 mg daily) and transdiagnostic cognitive behavioral treatment (CBT) alone and in combination on alcohol intake in subjects with co-morbid alcohol use disorders (AUDs) and anxiety disorders were compared. Drinking outcomes and anxiety were assessed for 81 subjects treated for 11 weeks with one of 4 conditions: 1) VEN-CBT, 2) VEN-Progressive Muscle Relaxation therapy (PMR), 3) Placebo (PLC)-CBT and 4) a comparison group of PLC-PMR. For subjects who reported taking at least one dose of study medication, the Time×Group interaction was significant for percent days of heavy drinking and drinks consumed per day. For the measure of percent days heavy drinking, the paired comparison of PLC-CBT versus PLC-PMR group indicated that the PLC-CBT group had greater drinking reductions, whereas other groups were not superior to the comparison group. In Week 11, the proportion of subjects in the PLC-CBT group that had a 50% reduction from baseline in percent days heavy drinking was significantly greater than those in the comparison group. Of the 3 "active treatment" groups only the PLC-CBT group had significantly decreased heavy drinking when contrasted to the comparison group. This finding suggests that the transdiagnostic CBT approach of Barlow and colleagues may have value in the management of heavy drinking in individuals with co-morbid alcoholism and anxiety.


Asunto(s)
Trastornos Relacionados con Alcohol/complicaciones , Trastornos Relacionados con Alcohol/terapia , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Terapia Combinada/métodos , Ciclohexanoles/uso terapéutico , Adulto , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Consumo de Bebidas Alcohólicas/terapia , Trastornos Relacionados con Alcohol/tratamiento farmacológico , Antidepresivos de Segunda Generación/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico , Ciclohexanoles/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Terapia por Relajación , Clorhidrato de Venlafaxina
10.
Circ Arrhythm Electrophysiol ; 6(4): 738-45, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23873140

RESUMEN

BACKGROUND: Myocardial infarction (MI) is associated with the development of atrial fibrillation (AF). We aimed to characterize the atrial abnormalities because of MI and determine the role of ischemia to the AF substrate. METHODS AND RESULTS: Forty-four sheep were studied. MI was induced by occlusion of the left circumflex artery (LCX) or left anterior descending artery (LAD). Excluding 11 with fatal arrhythmias, equal groups of animals (LCX; LAD; and sham-operated) underwent sequential electrophysiology study for 45 minutes to determine atrial effective refractory periods, conduction velocity, conduction heterogeneity index, and AF inducibility. Postmortem evaluation was performed with 2,3,5 triphenyl tetrazolium chloride staining. MI resulted in greater left ventricular dysfunction (P<0.05), LA pressure (P<0.0003), and reduction in atrial effective refractory periods (P<0.0001) compared with control. 2,3,5 triphenyl tetrazolium chloride staining demonstrated that the left circumflex artery, and not the LAD, group had atrial infarction. The left circumflex artery group demonstrated the following compared with the LAD or control groups: greater slowing in atrial conduction velocity (P<0.0001 and P<0.001); increased absolute range of conduction phase delay (P<0.001 and P<0.001); increased conduction heterogeneity index (P<0.0001 and P<0.001); greater AF vulnerability (P<0.05 for both); and longer AF duration (P<0.05 for both). LAD group had modest but significant slowing in conduction velocity (P<0.01) but no change in conduction heterogeneity index or AF duration compared with control. CONCLUSIONS: Left ventricular infarction, which is known to result in atrial stretch, hemodynamic change, and neurohumoral activation, contributes partially to the atrial abnormalities in MI. Atrial ischemia/infarction results in greater atrial electrophysiological changes and propensity for AF forming the dominant substrate for AF in MI.


Asunto(s)
Fibrilación Atrial/etiología , Función del Atrio Izquierdo , Infarto del Miocardio/complicaciones , Potenciales de Acción , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Presión Atrial , Modelos Animales de Enfermedad , Técnicas Electrofisiológicas Cardíacas , Atrios Cardíacos/patología , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Periodo Refractario Electrofisiológico , Factores de Riesgo , Ovinos , Factores de Tiempo , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda
11.
Bioorg Med Chem ; 20(3): 1251-8, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22261024

RESUMEN

Data on phytochemical constituents of plants commonly used in traditional Indonesian medicine have been compiled as a computer database. This database (the Indonesian Herbal constituents database, IHD) currently contains details on ∼1,000 compounds found in 33 different plants. For each entry, the IHD gives details of chemical structure, trivial and systematic name, CAS registry number, pharmacology (where known), toxicology (LD(50)), botanical species, the part(s) of the plant(s) where the compounds are found, typical dosage(s) and reference(s). A second database has been also been compiled for plant-derived compounds with known activity against the enzyme, aldose reductase (AR). This database (the aldose reductase inhibitors database, ARID) contains the same details as the IHD, and currently comprises information on 120 different AR inhibitors. Virtual screening of all compounds in the IHD has been performed using Random Forest (RF) modelling, in a search for novel leads active against AR-to provide for new forms of symptomatic relief in diabetic patients. For the RF modelling, a set of simple 2D chemical descriptors were employed to classify all compounds in the combined ARID and IHD databases as either active or inactive as AR inhibitors. The resulting RF models (which gave misclassification rates of 21%) were used to identify putative new AR inhibitors in the IHD, with such compounds being identified as those giving RF scores >0.5 (in each of the three different RF models developed). In vitro assays were subsequently performed for four of the compounds obtained as hits in this in silico screening, to determine their inhibitory activity against human recombinant AR. The two compounds having the highest RF scores (prunetin and ononin) were shown to have the highest activities experimentally (giving ∼58% and ∼52% inhibition at a concentration of 15µM, respectively), while the compounds with lowest RF scores (vanillic acid and cinnamic acid) showed the lowest activities experimentally (giving ∼29% and ∼44% inhibition at a concentration of 15µM, respectively). These simple virtual screening studies were thus helpful in identifying novel inhibitors of AR, but yielded compounds with only very modest (micromolar) potency.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Plantas Medicinales/química , Aldehído Reductasa/metabolismo , Inteligencia Artificial , Simulación por Computador , Bases de Datos Factuales , Humanos , Indonesia , Modelos Biológicos , Programas Informáticos
12.
Bioorg Med Chem ; 18(6): 2204-2218, 2010 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-20188577

RESUMEN

Chinese herbs were screened for compounds which may be active against four targets involved in inflammation, using pharmacophore-assisted docking. Multiple LigandScout (LS) pharmacophores built from ligand-receptor complexes in the protein databank (PDB) were first employed to select compounds. These compounds were then docked using LS-derived templates and ranked according to docking score. The targets comprised cyclo-oxygenases 1 & 2 (COX), p38 MAP kinase (p38), c-Jun terminal-NH(2) kinase (JNK) and type 4 cAMP-specific phosphodiesterase (PDE4). The results revealed that multi-target inhibitors are likely to be relatively common in Chinese herbs. Details of their distribution are given, in addition to experimental evidence supporting these results. Examples of compounds predicted to be active against at least three targets are presented, and their features outlined. The distribution of herbs containing predicted inhibitors was also analysed in relation to 192 Chinese formulas from over 50 herbal categories. Among those found to contain a high proportion of these herbs were formulas traditionally used to treat fever, headache, rheumatoid arthritis, inflammatory bowel disorders, skin disease, cancer, and traumatic injury. Relationships between multi-target drug discovery and Chinese medicine are discussed.


Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Inhibidores Enzimáticos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Fosfodiesterasa 4 , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Antiinflamatorios/química , Cristalografía por Rayos X , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Bases de Datos Factuales , Diseño de Fármacos , Medicamentos Herbarios Chinos/química , Inhibidores Enzimáticos/química , Medicina Tradicional China , Modelos Químicos , Modelos Moleculares , Conformación Molecular , Relación Estructura-Actividad
13.
J Clin Oncol ; 28(6): 967-75, 2010 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-20065185

RESUMEN

PURPOSE To investigate the management of bone health in women with early breast cancer (EBC) who were scheduled to receive anastrozole. PATIENTS AND METHODS Postmenopausal women with hormone receptor-positive EBC were assigned to one of three strata by risk of fragility fracture. Patients with the highest risk (H) received anastrozole 1 mg/d plus risedronate 35 mg/wk orally. Patients with moderate-risk (M) were randomly assigned in a double-blind manner to anastrozole and risedronate (A + R) or to anastrozole and placebo (A + P). Patients with lower-risk (L) received anastrozole (A) alone. Calcium and vitamin D were recommended for all patients. Lumbar spine and total hip bone mineral density (BMD) were assessed at baseline, 12 months, and 24 months. Results At 24 months, in the M group, treatment with A + R resulted in a significant increase in lumbar spine and total hip BMD compared with A + P treatment (2.2% v -1.8%; treatment ratio, 1.04; P < .0001; and 1.8% v -1.1%; treatment ratio, 1.03; P < .0001, respectively). In the H stratum, lumbar spine and total hip BMD increased significantly (3.0%; P = .0006; and 2.0%; P = .0104, respectively). Patients in the L stratum showed a significant decrease in lumbar spine BMD (-2.1%; P = .0109) and a numerical decrease in total hip BMD (-0.4%; P = .5988). Safety profiles for anastrozole and risedronate were similar to those already established. CONCLUSION In postmenopausal women at risk of fragility fracture who were receiving adjuvant anastrozole for EBC, the addition of risedronate at doses established for preventing and treating osteoporosis resulted in favorable effects in BMD during 24 months.


Asunto(s)
Inhibidores de la Aromatasa/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ácido Etidrónico/análogos & derivados , Fracturas Óseas/prevención & control , Nitrilos/efectos adversos , Osteoporosis Posmenopáusica/prevención & control , Triazoles/efectos adversos , Anciano , Anastrozol , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/patología , Método Doble Ciego , Ácido Etidrónico/uso terapéutico , Femenino , Fracturas Óseas/inducido químicamente , Terapia de Reemplazo de Hormonas , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Osteoporosis Posmenopáusica/inducido químicamente , Posmenopausia , Pronóstico , Ácido Risedrónico , Tasa de Supervivencia , Resultado del Tratamiento
14.
Biochim Biophys Acta ; 1788(2): 477-83, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19118517

RESUMEN

The size and the bilayer thickness of detergent-resistant membranes isolated from rat brain neuronal membranes using Triton X-100 or Brij 96 in buffers with or without the cations, K+/Mg2+ at a temperature of either 4 degrees C or 37 degrees C were determined by dynamic light scattering and small-angle neutron scattering. Regardless of the precise conditions used, isolated membrane preparations consisted of vesicles of approximately 100 to 200 nm diameter as determined by dynamic light scattering methods, equating to an area of the lipid based membrane microdomain size of 200 to 400 nm diameter. By means of small angle neutron scattering it was established that the average thickness of the bilayers of the complete population of detergent-resistant membranes was similar to that of the parental membrane at between 4.6 and 5.0 nm. Detergent-resistant membranes prepared using buffers containing K+/Mg2+ uniquely formed unilamellar vesicles while membranes prepared in the absence of K+/Mg2+ formed a mixture of uni- and oligolamellar structures indicating that the arrangement of the membrane differs from that observed in the presence of cations. Furthermore, the detergent-resistant membranes prepared at 37 degrees C were slightly thicker than those prepared at 4 degrees C, consistent with the presence of a greater proportion of lipids with longer, more saturated fatty acid chains associated with the Lo (liquid-ordered) phase. It was concluded that the preparation of detergent-resistant membranes at 37 degrees C using buffer containing cations abundant in the cytoplasm might more accurately reflect the composition of lipid rafts present in the plasma membrane under physiological conditions.


Asunto(s)
Química Encefálica , Encéfalo/efectos de los fármacos , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Octoxinol/farmacología , Aceites de Plantas/farmacología , Polietilenglicoles/farmacología , Animales , Membrana Dobles de Lípidos/química , Ratas
15.
J Chem Inf Model ; 47(6): 2316-34, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17929800

RESUMEN

Distribution patterns of 8411 compounds from 240 Chinese herbs were analyzed in relation to the herbal categories of traditional Chinese medicine (TCM), using Random Forest (RF) and self-organizing maps (SOM). RF was used first to construct TCM profiles of individual compounds, which describe their affinities for 28 major herbal categories, while simultaneously minimizing the level of noise associated with the complex array of diverse phytochemicals found in herbs from each category. Profiles were then reduced and visualized with SOM. The distribution of 10 major phytochemical classes, in relation to TCM profile, was delineated with SOM-Ward clustering. These classes comprised aliphatics, alkaloids, simple phenolics, lignans, quinones, polyphenols (flavonoids and tannins), and mono-, sesqui-, di-, and triterpenes (including sterols). Highly distinctive patterns of association between phytochemical class and TCM profile were revealed, suggesting that a strong phytochemical basis underlies the traditional language of Chinese medicine. Maps trained after random permutation of herbs assigned to each category were, by contrast, devoid of feature, providing additional evidence for the significance of these associations. Most classes were split into relatively few clusters, and further analysis revealed that simple descriptors, comprising skeletal type, molecular weight, and calculated log P, were in most cases able to readily discriminate within-class clusters. Relationships between TCM profile and predicted activities, relating to therapeutically important molecular targets, were explored and indicate that ethnopharmacological data could play an important role in pharmaceutical prospecting from Chinese herbs as well as identifying links between Chinese and Western medicine.


Asunto(s)
Biología Computacional/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Bases de Datos Factuales , Medicamentos Herbarios Chinos/clasificación , Datos de Secuencia Molecular , Estructura Molecular
16.
J Chem Inf Model ; 47(2): 254-63, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17381164

RESUMEN

Two databases have been constructed to facilitate applications of cheminformatics and molecular modeling to medicinal plants. The first contains data on known chemical constituents of 240 commonly used Chinese herbs, the other contains information on target specificities of bioactive plant compounds. Structures are available for all compounds. In the case of the Chinese herbal constituents database, further details include trivial and systematic names, compound class and skeletal type, botanical and Chinese (pinyin) names of associated herb(s), CAS registry number, chirality, pharmacological and toxicological information, and chemical references. For the bioactive plant compounds database, details of molecular target(s), IC50 and related measures, and associated botanical species are given. For Chinese herbs, approximately 7000 unique compounds are listed, though some are found in more than one herb, the total number for all herbs being 8264. For bioactive plant compounds, 2597 compounds active against 78 molecular targets are covered. Statistical relationships within and between the two databases are explored.


Asunto(s)
Bases de Datos Factuales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Biología Computacional , Bases de Datos Factuales/estadística & datos numéricos , Ligandos , Estructura Molecular , Especificidad por Sustrato , Factores de Tiempo
17.
J Chem Inf Model ; 47(2): 264-78, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17381165

RESUMEN

Random Forest, a form of multiple decision trees, has been used to screen a database of Chinese herbal constituents for potential inhibitors against several therapeutically important molecular targets. These comprise cyclic adenosine 3'-5'-monophosphate phosphodiesterases, protein kinase A, cyclooxygenases, lipoxygenases, aldose reductase, and three HIV targets-integrase, protease, and reverse transcriptase. In addition, compounds were identified which may inhibit the expression of inducible nitric oxide synthase and/or nitric oxide production in vivo. A total of 240 Chinese herbs containing 8264 compounds were screened in silico, including many used on a regular basis in traditional Chinese medicine. Active compounds were selected from another database of 2597 phytochemicals and related natural products with known target affinities and covered a wide range of structural classes. Random Forest was found to perform well, even on highly unbalanced data characteristic of ligand-based screening where the compounds to be screened are far more numerous than the number of active compounds used in training. Despite a conservative screening protocol, a wide variety of compounds from Chinese herbs were hit. Of particular interest were the relatively large number of herbs predicted to inhibit multiple targets, as well as a number which appeared to contain inhibitors of the same target from different phytochemical classes. The latter point to the possibility that individual species may make use of alternative phytochemical strategies in target inhibition. A literature search provided evidence to support 83 herb-target predictions.


Asunto(s)
Árboles de Decisión , Evaluación Preclínica de Medicamentos/métodos , Medicamentos Herbarios Chinos/farmacología , Biología Computacional/métodos , Concentración 50 Inhibidora , Transducción de Señal/efectos de los fármacos
18.
J Pharm Sci ; 91(11): 2317-31, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12379917

RESUMEN

Total-intensity light scattering (TILS) and photon correlation spectroscopy (PCS) techniques have been used to determine the droplet size of concentrated, oil-in-water microemulsions formed from soybean oil, polyoxyethylene-10-oleyl ether (C(18:1)E(10)), and water, both in the presence and absence of the lipophilic drug, testosterone enanthate. The TILS data were analyzed using the hard-sphere model of Percus-Yevick to account for interparticulate interactions experienced in the concentrated systems studied and the volume fraction of the hard-sphere droplet obtained from these analyses used to correct the PCS data. Correction of the light-scattering data in this manner yielded a satisfactory agreement between the size of the microemulsion droplets calculated using both techniques. Both the TILS and PCS data showed that, for a constant surfactant concentration, the size of the microemulsion droplets increased with increasing oil content. For example, droplets of radius 52.5 and 65.1 A (as determined by TILS) were obtained at 10.0% w/w C(18:1)E(10) and 0.5 and 2.0% w/w soybean oil, respectively. In contrast, for a constant oil concentration, microemulsion droplet size decreased with increasing surfactant concentration. For example, droplet sizes of 65.1, 59.3, 56.6, 54.5, and 53.3 A were seen with 2.0% w/w soybean oil and 10, 14.0, 18, 22, or 26% w/w C(18:1)E(10), respectively. Furthermore, in the presence of 1.0% w/w of the lipophilic drug, testosterone enanthate, the size of the microemulsion droplet increased by about 6-10 A depending on the concentration of the surfactant; the higher the concentration of the surfactant, the smaller the increase in size. The slight increase in size of the drug-containing microemulsion droplets suggests that some of the drug has penetrated into the core of the droplet.


Asunto(s)
Polietilenglicoles/química , Aceite de Soja/química , Testosterona/análogos & derivados , Testosterona/química , Emulsiones , Análisis Espectral/métodos , Agua
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