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1.
Dis Aquat Organ ; 143: 13-18, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33506811

RESUMEN

Neoplasia is rarely reported in decapod crustaceans, and sarcoma has not been previously reported in any crab species. A California king crab Paralithodes californiensis with a recent history of autotomy (4 legs lost) and anorexia was found dead. Grossly, the crab had a pigmented ulcer on the right cheliped merus. Necropsy tissue samples were placed in 10% neutral buffered formalin and processed routinely for histology. Both histochemical (i.e. Brown and Brenn Gram, Fite-Faraco acid fast, Fontana-Masson, Giemsa, hematoxylin and eosin, Masson's trichrome, periodic acid-Schiff [PAS], phosphotungstic acid-hematoxylin, and von Kossa) and immunohistochemical (i.e. cytokeratin, vimentin, and lysozyme) stains were performed. The body wall (presumably of the right cheliped merus) was ulcerated and subtended by a densely cellular, unencapsulated, invasive neoplasm composed of spindle cells arranged in intersecting streams and bundles embedded in a small to moderate amount of fibromatous stroma. Neoplastic cells were oval to elongate with fibrillar, pale eosinophilic cytoplasm that occasionally contained moderate numbers of small, spherical, brightly eosinophilic granules that were highlighted with PAS and Giemsa stains. Neoplastic cells had mild atypia and no evident mitoses. Immunohistochemical stains were noncontributory. This neoplasm is consistent with hemocytic sarcoma of semi-granulocytic origin. Decapod crustaceans have 3 types of hemocytes: hyalinocytes, granulocytes, and semi-granulocytes. Neoplastic cells had PAS- and Giemsa-positive granules, which are present in both semi-granulocytes and granulocytes. Semi-granulocytes can elongate and are associated with deposition of extracellular matrix during some immune responses. Neoplastic cells were elongate and associated with deposition of matrix. These findings suggest neoplastic cells were of semi-granulocytic origin.


Asunto(s)
Anomuros , Braquiuros , Sarcoma , Animales , California , Hemocitos , Sarcoma/veterinaria
2.
IEEE Trans Biomed Eng ; PP2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302790

RESUMEN

OBJECTIVE: Our aim is to determine if data collected with inertial measurement units (IMUs) during steady-state running could be used to estimate ground reaction forces (GRFs) and to derive biomechanical variables (e.g., contact time, impulse, change in velocity) using lightweight machine-learning approaches. In contrast, state-of-the-art estimation using LSTMs suffers from prohibitive inference times on edge devices, requires expensive training and hyperparameter optimization, and results in black box models. METHODS: We proposed a novel lightweight solution, SVD Embedding Regression (SER), using linear regression between SVD embeddings of IMU data and GRF data. We also compared lightweight solutions including SER and k-Nearest-Neighbors (KNN) regression with state-of-the-art LSTMs. RESULTS: We performed extensive experiments to evaluate these techniques under multiple scenarios and combinations of IMU signals and quantified estimation errors for predicting GRFs and biomechanical variables. We did this using training data from different athletes, from the same athlete, or both, and we explored the use of acceleration and angular velocity data from sensors at different locations (sacrum and shanks). CONCLUSION: Our results illustrated that lightweight solutions such as SER and KNN can be similarly accurate or more accurate than LSTMs. The use of personal data reduced estimation errors of all methods, particularly for most biomechanical variables (as compared to GRFs); moreover, this gain was more pronounced in the lightweight methods. SIGNIFICANCE: The study of GRFs is used to characterize the mechanical loading experienced by individuals in movements such as running, which is clinically applicable to identify athletes at risk for stress-related injuries.

3.
Sports Biomech ; 12(2): 121-31, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23898685

RESUMEN

During the golf swing, the reaction forces applied at the feet control translation and rotation of the body-club system. In this study, we hypothesized that skilled players using a 6-iron would regulate shot distance by scaling the magnitude of the resultant horizontal reaction force applied to the each foot with minimal modifications in force direction. Skilled players (n = 12) hit golf balls using a 6-iron. Shot distance was varied by hitting the ball as they would normally and when reducing shot distance using the same club. During each swing, reaction forces were measured using dual force plates (1200 Hz) and three-dimensional kinematics were simultaneously captured (110 Hz). The results indicate that, on average, the peak resultant horizontal reaction forces of the target leg were significantly less than normal (5%, p < 0.05) when reducing shot distance. No significant differences in the orientation of the peak resultant horizontal reaction forces were observed. Resultant horizontal reaction force-angle relationships within leg and temporal relationships between target and rear legs during the swing were consistent within player across shot conditions. Regulation of force magnitude with minimal modification in force direction is expected to provide advantages from muscle activation, coordination, and performance points of view.


Asunto(s)
Pie/fisiología , Golf/fisiología , Adolescente , Adulto , Fenómenos Biomecánicos , Humanos , Imagenología Tridimensional , Grabación en Video , Adulto Joven
4.
J Microsc ; 247(3): 220-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22906009

RESUMEN

Focused ion beam milling at cryogenic temperatures (cryo-FIB) is a valuable tool that can be used to thin vitreous biological specimens for subsequent imaging and analysis by cryo-transmission electron microscopy (cryo-TEM) in a frozen-hydrated state. This technique offers the potential benefit of eliminating the mechanical artefacts that are typically found with cryo-ultramicrotomy. However, due to the additional complexity in transferring samples in and out of the FIB, contamination and devitrification of the amorphous ice is commonly encountered. To address these problems, we have designed a sample cryo-shuttle that directly and specifically accepts Polara TEM cartridges to simplify the transfer process between FIB and TEM. We optimized several parameters in the cryo-FIB and cryo-TEM processes using the quality of the samples' ice as an indicator and demonstrated high-quality milling with large mammalian cells. By comparing the results from HeLa cells to those from Escherichia coli cells, we discuss some of the artefacts and challenges we have encountered using this technique.


Asunto(s)
Artefactos , Microscopía por Crioelectrón/métodos , Escherichia coli/ultraestructura , Microscopía Electrónica de Transmisión/métodos , Animales , Microscopía por Crioelectrón/instrumentación , Criopreservación/instrumentación , Criopreservación/métodos , Crioultramicrotomía/métodos , Células HeLa , Humanos , Aumento de la Imagen/métodos , Mamíferos , Microscopía Electrónica de Transmisión/instrumentación , Manejo de Especímenes/métodos
5.
Environ Sci Technol ; 46(10): 5336-43, 2012 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-22540536

RESUMEN

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40-90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.


Asunto(s)
Monitoreo del Ambiente , Hormonas/análisis , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos , Movimientos del Agua , Contaminantes Químicos del Agua/análisis , Vermont , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua
6.
J Electromyogr Kinesiol ; 62: 102340, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31387793

RESUMEN

Understanding how individuals distribute mechanical demand imposed on their upper extremity during physically demanding activities provides meaningful insights to preserve function and mitigate detrimental mechanical loading of the shoulder. In this study, we hypothesized that parameterization of the shoulder net joint moment using four functional axes could characterize distribution tendencies about the shoulder during manual wheelchair propulsion and that regardless of demographics, a shoulder flexor dominant NJM distribution would be predominantly used by individuals with paraplegia (n = 130). Forces and kinematics of the upper extremity and trunk were quantified using motion capture and an instrumented wheel during steady state manual wheelchair propulsion at self-selected fast speeds on a stationary ergometer. The results indicate that parsing out the internal/external rotation component of the shoulder net joint moment about the upper arm and distributing the remainder across the three orthogonal axes of the torso was successful in identifying common shoulder net joint moment distribution techniques used across individuals with paraplegia during manual wheelchair propulsion. Distribution tendencies were predominantly flexor dominant across injury level, gender, time since injury, body mass index, and height demographics. The 4-axis parameterization of the shoulder NJM effectively differentiated moment distribution tendencies used by individuals during manual wheelchair propulsion using a functionally relevant representation of shoulder kinetics. Use of the four-axis parameterization of joint kinetics in future studies is expected to provide important insights that can advance knowledge, preserve function, and inform clinical decisions.


Asunto(s)
Articulación del Hombro , Silla de Ruedas , Fenómenos Biomecánicos , Humanos , Músculo Esquelético , Hombro
7.
J Biomech ; 39(6): 990-1000, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-15878165

RESUMEN

Observation of complex whole body movements suggests that the nervous system coordinates multiple operational subsystems using some type of hierarchical control. When comparing two forward translating tasks performed with and without backward angular impulse, we have learned that both trunk-leg coordination and reaction force-time characteristics are significantly different between tasks. This led us to hypothesize that differences in trunk-leg coordination and reaction force generation would induce between-task differences in the control of the lower extremity joints during impulse generation phase of the tasks. Eight highly skilled performers executed a series of forward jumps with and without backward rotation (reverse somersault and reverse timer, respectively). Sagittal plane kinematics, reaction forces, and electromyograms of lower extremity muscles were acquired during the take-off phase of both tasks. Lower extremity joint kinetics were calculated using inverse dynamics. The results demonstrated between-task differences in the relative angles between the lower extremity segments and the net joint forces/reaction force and the joint angular velocity profiles. Significantly less knee extensor net joint moments and net joint moment work and greater hip extensor net joint moments and net joint moment work were observed during the push interval of the reverse somersault as compared to the reverse timer. Between-task differences in lower extremity joint kinetics were regulated by selectively activating the bi-articular muscles crossing the knee and hip. These results indicate that between-task differences in the control of the center of mass relative to the reaction force alters control and dynamics of the multijoint lower extremity subsystem.


Asunto(s)
Gimnasia/fisiología , Extremidad Inferior/fisiología , Movimiento/fisiología , Contracción Muscular/fisiología , Desempeño Psicomotor/fisiología , Adulto , Fenómenos Biomecánicos , Buceo/fisiología , Electromiografía , Femenino , Articulación de la Cadera/fisiología , Humanos , Articulación de la Rodilla/fisiología , Masculino , Estados Unidos
8.
Arch Gen Psychiatry ; 38(8): 910-5, 1981 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7259425

RESUMEN

We have studied the interaction between boyhood cross-gender behavior, "homophobia," and religiosity in men raised as Catholics who, during adulthood, considered themselves transsexual, homosexual, or heterosexual. The sample consisted of 43 transsexual, 78 homosexual, and 43 heterosexual subjects matched for age, race, educational level, and economic status. The transsexual men recalled the most "feminine" behavior during boyhood, followed by the homosexual men. The heterosexual group was most "homophobic," followed by the transsexuals. "Homophobia" positively correlated with religiosity among adult transsexuals and heterosexuals. Transsexuals, recalling childhood, perceived their parents as being more religious than did the homosexuals. At intermediate levels of "femininity," greater "homophobia" scores were associated with more transsexual characteristics. These data support the thesis that early developmental aspects of sexual identity, and later concerns over homosexuality that are partly of a religious derivative, may contribute to a transsexual outcome.


Asunto(s)
Identidad de Género , Homosexualidad , Identificación Psicológica , Religión y Psicología , Transexualidad/psicología , Actitud , Catolicismo , Humanos , Masculino , Travestismo/psicología
9.
Clin Biomech (Bristol, Avon) ; 20(1): 105-11, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15567544

RESUMEN

OBJECTIVE: Sit-to-stand tasks are commonly facilitated by modifying the initial position of the center of mass relative to the feet. It was hypothesized that modifications in the center of mass trajectory during sit-to-stand tasks altered the total body momentum at seat departure and redistributed the lower extremity net joint moments. DESIGN: Between-task within-subject comparison was employed using a robust statistical method to accommodate for small sample size. METHODS: Six individuals performed four sit-to-stand tasks with systematic modifications in the initial center of mass position by varying the orientation of the lower extremity segments. The momentum of the center of mass and lower extremity net joint moments were quantified and compared. RESULTS: Reducing the horizontal center of mass displacement significantly reduced horizontal total body momentum required at seat departure. Sit-to-stand tasks initiated with more horizontal shank and thigh positions required significantly greater knee and hip extensor net joint moments than those with more vertical shank and thigh positions. Sit-to-stand tasks initiated with vertical shank positions also required significantly greater hip extensor net joint moments as compared to those with more horizontal shank orientations. INTERPRETATION: When changes in initial center of mass position are made, alteration in center of mass horizontal momentum and the orientation of the lower extremity segments relative to the reaction force are observed. Consequently, mechanical demand imposed on the ankle, knee, and hip joint is redistributed. The magnitude of the net joint moments is dependent on the segment orientation, the reaction force, and the adjacent net joint moment.


Asunto(s)
Articulaciones/fisiología , Extremidad Inferior/fisiología , Movimiento/fisiología , Postura/fisiología , Desempeño Psicomotor/fisiología , Soporte de Peso/fisiología , Adaptación Fisiológica/fisiología , Adulto , Fenómenos Biomecánicos/métodos , Femenino , Humanos , Masculino , Estrés Mecánico , Torque
10.
Cardiovasc Res ; 35(3): 505-13, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9415295

RESUMEN

OBJECTIVES: Gene therapy may provide new approaches to reduce vein graft failure following coronary or peripheral bypass surgery. The aim of this study was to investigate the relative efficacy of intraoperative adenoviral gene transfer to vein grafts, comparing transgene expression in vein grafts with that in matched native vessels in the same animal. In addition, we assessed the impact of bypass grafting on the cellular targets of gene transfer. METHODS: New Zealand White rabbits underwent interposition bypass grafting of the carotid artery, using the ipsilateral external jugular vein, which was infected with an adenovirus expressing beta-galactosidase immediately prior to bypass grafting (n = 16). The contralateral native jugular vein (n = 16) and carotid artery (n = 8) were infected concurrently with the same adenoviral preparation. After 3, 7 or 14 days, beta-galactosidase protein expression was quantified by ELISA, and specific cell types expressing beta-galactosidase were identified by X-Gal staining and by immunohistochemistry. RESULTS: After 3 days, endothelial cells were efficiently transduced in all vessels; medial smooth muscle cells were transduced infrequently. In contrast to jugular veins after gene transfer, endothelium in vein grafts showed expression of VCAM-1 and ICAM-1, and intense inflammation with CD18+ leukocytes. Transgene expression in vein grafts at day 3 was maintained at levels approximately 50% of that in ungrafted jugular veins, but continued to decrease through day 7. CONCLUSIONS: Although vascular injury in early venous bypass grafts reduces gene transfer efficacy, significant transgene expression is maintained for at least 7 days. These findings have important implications for intraoperative gene transfer strategies in vein grafts.


Asunto(s)
Adenoviridae , Estenosis Carotídea/terapia , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Venas Yugulares/trasplante , Animales , Endotelio Vascular/enzimología , Ensayo de Inmunoadsorción Enzimática , Expresión Génica , Inmunohistoquímica , Masculino , Músculo Liso Vascular/enzimología , Conejos , Factores de Tiempo , beta-Galactosidasa/genética
11.
J Interferon Cytokine Res ; 18(12): 1019-24, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9877444

RESUMEN

We describe a novel MxA gene-induction assay for type I interferons (IFN-alpha and IFN-beta) based on the specific induction of the MxA gene in cultured human cells. Accumulated intracellular MxA protein is determined by immunologic measurement by a rapid method using commercially available materials. IFN activity can be measured accurately over a concentration range of 0.1-30 IU/ml. In contrast, type II IFN and other cytokines are not significantly detected. The MxA-induction assay has advantages in terms of specificity, reliability, and sensitivity over other methods for assaying type I IFN. It has also been adapted and validated for measuring the titers of anti-IFN-beta neutralizing antibodies in human sera.


Asunto(s)
Antivirales/genética , Bioensayo , Proteínas de Unión al GTP , Inductores de Interferón/farmacología , Interferón Tipo I/biosíntesis , Proteínas/genética , Antivirales/farmacocinética , Línea Celular , Semivida , Humanos , Proteínas de Resistencia a Mixovirus , Pruebas de Neutralización , Proteínas/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Células Tumorales Cultivadas
12.
J Interferon Cytokine Res ; 18(12): 1025-30, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9877445

RESUMEN

We have adapted the new MxA gene-induction bioassay to measure neutralizing antibodies to interferon-beta1b (IFN-beta1b, the active ingredient in Betaseron) in sera from patients treated with Betaseron. This antibody assay has been validated to quantify neutralizing titers of 1:20 and above, with a precision of +/- 0.20 in log10. We have used this MxA gene-induction antibody assay to reinvestigate serum samples from multiple sclerosis (MS) patients treated with Betaseron. The titers measured were closely comparable to those obtained in antiviral assays. Data obtained by both methods show that neutralizing antibodies may appear and subsequently disappear over time in the sera of some patients treated with Betaseron. Sera from some patients contain binding antibodies to IFN-beta1b. It was shown that binding antibody titers do not correlate quantitatively or qualitatively with neutralizing antibody titers, and indeed, a number of patients develop high levels of binding antibodies but never form measurable levels of neutralizing antibodies.


Asunto(s)
Reacciones Antígeno-Anticuerpo , Proteínas de Unión al GTP , Inmunoglobulina G/inmunología , Interferón beta/inmunología , Antivirales/inmunología , Bioensayo , Humanos , Interferón beta-1a , Interferon beta-1b , Proteínas de Resistencia a Mixovirus , Proteínas/inmunología , Proteínas Recombinantes/inmunología , Método Simple Ciego
13.
Neurology ; 27(10): 921-7, 1977 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-561904

RESUMEN

Four subjects with orthostatic hypotension were given intravenous infusions of methoxamine and isoproterenol. Methoxamine caused an elevation in systolic blood pressure. Isoproterenol resulted in a fall in blood pressure in three of the subjects. The heart rate decreased with methoxamine, but increased with isoproterenol. The responsivity in orthostatic hypotension was compatible with denervation supersensitivity. These effects were compared with the responsivity to methoxamine and isoproterenol of five labile hypertensives. Two patients with severe orthostatic hypotension were treated with regimens including levodopa. Levodopa alone would further aggravate postural hypotension. But in one subject given levodopa, ephedrine, and fludrocortisone and in the other managed on levodopa, tranylcypromine, and fludrocortisone, symptomatic orthostatic hypotension was successfully eliminated. These results support the usefulness of levodopa, in combination with adrenergic agents, as a therapeutic measure for advanced forms of orthostatic hypotension.


Asunto(s)
Hipotensión Ortostática/tratamiento farmacológico , Levodopa/uso terapéutico , Simpatomiméticos/farmacología , Fibras Adrenérgicas/efectos de los fármacos , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Dopamina beta-Hidroxilasa/sangre , Evaluación de Medicamentos , Quimioterapia Combinada , Efedrina/uso terapéutico , Femenino , Fludrocortisona/uso terapéutico , Humanos , Isoproterenol/farmacología , Masculino , Metoxamina/farmacología , Persona de Mediana Edad , Renina/sangre , Tranilcipromina/uso terapéutico , Ácido Vanilmandélico/orina
14.
Am J Med ; 83(5): 817-23, 1987 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-3674089

RESUMEN

Strictly enforced formulary restrictions for aminoglycosides, cephalosporins, and a vancomycin group generated combined savings of $2.61 (p less than 0.0046) per antibiotic day and $34,597 (p less than 0.0003) per month. Even after some cost increases (not significant) in new and other antibiotics, the program saved $1.33 (p less than 0.0175) per antibiotic day and $24,620 (p less than 0.0311) per month for all antibiotics. The pharmacy's 1985 average cost per antibiotic day and its monthly expenditures were $18.45 and $199,003, respectively. In the months following the formulary restrictions, no significant detrimental changes occurred in hospital length of stay or mortality. A retrospective analysis of 322 patients with bacteremia treated before and after the onset of the controls revealed that antibiotics were more appropriately used afterwards.


Asunto(s)
Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Formularios de Hospitales como Asunto/economía , Hospitales de Enseñanza/economía , Servicio de Farmacia en Hospital/economía , Vancomicina/uso terapéutico , Aminoglicósidos , Control de Costos , Costos y Análisis de Costo , Utilización de Medicamentos/economía , Hospitales con más de 500 Camas , Humanos , Missouri , Análisis de Regresión , Estudios Retrospectivos , Sepsis/tratamiento farmacológico
15.
Am J Med ; 87(3): 253-9, 1989 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2773963

RESUMEN

PURPOSE: Inappropriate antimicrobial use was examined among a randomly and prospectively selected cohort of patients with at least one positive result of blood cultures. This misuse was then analyzed with respect to hospital charges and length of stay (LOS). PATIENTS AND METHODS: The study consisted of 70 patients (average age, 58.5 years) who had not undergone bone marrow transplantation. Patient charts were reviewed daily for the following information: clinical signs and symptoms of infection, pertinent laboratory data, culture results, detailed data on each antimicrobial in every antimicrobial regimen and their appropriateness, hospital charges, LOS, diagnostic and procedure codes, and discharge status. Three severity of illness variables were generated. Inappropriate antimicrobial use was described according to one of 12 categories. RESULTS: The percent of antimicrobial misuse, defined as the proportion of days of administration of antimicrobials on which one or more antimicrobials were judged inappropriate, was found to be 22.3%. After adjustment for severity of illness and diagnosis, this average inappropriateness correlated with 4.2 additional hospitalization days and $5,368 additional hospital charges. CONCLUSION: Our results cannot distinguish among several possible reasons for these associations, including direct causality (e.g., toxicity and prolonged hospitalization for antimicrobial use) and indirect links such as inappropriate utilization of other resources and influences of severity of illness on antimicrobial use not accounted for in our equations. Nevertheless, the magnitude of the association gives import to the desirability of further studies.


Asunto(s)
Antiinfecciosos/administración & dosificación , Utilización de Medicamentos/economía , Infecciones/tratamiento farmacológico , Estudios de Cohortes , Costos y Análisis de Costo , Cuidados Críticos/economía , Esquema de Medicación , Economía Hospitalaria , Femenino , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Missouri , Estudios Prospectivos , Distribución Aleatoria , Índice de Severidad de la Enfermedad
16.
J Med Chem ; 36(20): 2886-90, 1993 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-8411004

RESUMEN

Previous studies have shown that 3 beta-(substituted phenyl)tropan-2 beta-carboxylic acid esters possess high affinity for the cocaine binding site on the dopamine transporter both in vitro and in vivo and inhibit dopamine uptake in vitro. Since 1,2,4-oxadiazoles are excellent bioisosteres of ester groups, we have prepared several 3 beta-(substituted phenyl)-2 beta-(3-substituted 1',2',4'-oxadiazol-5'-yl)tropanes (5b-h) and all four stereoisomers of (1R,5S)-3 phenyl-2-(3-methyl-1',2',4'-oxadiazol-5'-yl)tropane (5a and 6-8). The 3 alpha-phenyl-2-alpha-(3'-methyl-1',2',4'-oxadiazole) isomer 7 was prepared from a stereoselective addition of phenyllithium to (1R,5S)-2-(3'-methyl-1',2',4'-oxadiazol-5-yl)-8-methyl-8- azabicyclo[3.2.1]oct-2-ene (11). The binding affinities for 5a-h and 6-8 at the dopamine, serotonin, and norepinephrine transporters were obtained. In general these bioisosteres showed potencies for the dopamine transporter similar to those of their parent esters. 3 beta-(4'-Chlorophenyl)-2 beta-(3'-phenyl-1',2',4'-oxadiazol-5'-yl)tropane (5d) was the most potent analogue with an IC50 of 1.62nM. However, 3 beta-(4'-chlorophenyl)-2 beta-(3'-methoxyphenyl-1',2'4'- oxadiazol-5'-yl)tropane (5e) with an IC50 of 1.81 nM was the most selective analogue for the dopamine transporter showing NE/DA and 5-HT/DA ratios of 461 and 186, respectively. The cis- and trans-3 alpha-phenyl-2-(3'-methyl-1',2',4'-oxadiazol-5'-yl)tropanes (7 and 8), which exist in a boat conformation, have IC50 values only slightly greater than that of the 3 beta,2 beta-isomer (5a) which possesses the cocaine stereochemistry.


Asunto(s)
Proteínas Portadoras/metabolismo , Cocaína/análogos & derivados , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Simportadores , Tropanos/metabolismo , Animales , Sitios de Unión , Encéfalo/metabolismo , Cocaína/química , Cocaína/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Masculino , Estructura Molecular , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Estereoisomerismo , Relación Estructura-Actividad , Tropanos/síntesis química , Tropanos/química
17.
J Med Chem ; 38(2): 379-88, 1995 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-7830281

RESUMEN

Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3 beta-(4'-methylphenyl)- and 3 beta-(4'-chlorophenyl)tropane-2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3 beta-(4'-chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N- pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3 beta-(4'-iodophenyl)-tropane-2 beta-carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist.


Asunto(s)
Proteínas Portadoras/metabolismo , Cocaína/farmacología , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Amidas , Animales , Ácidos Carboxílicos , Corteza Cerebral/metabolismo , Fenómenos Químicos , Química Física , Cocaína/análogos & derivados , Cocaína/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Ésteres , Mesencéfalo/metabolismo , Norepinefrina/metabolismo , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo
18.
Am J Cardiol ; 82(9): 1077-81, 1998 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-9817485

RESUMEN

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.


Asunto(s)
Estenosis Carotídea/fisiopatología , Estenosis Carotídea/terapia , Stents , Anciano , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
19.
Arch Surg ; 126(10): 1231-5; discussion 1235-6, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1929823

RESUMEN

Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/- 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome.


Asunto(s)
Síndrome de Vaciamiento Rápido/prevención & control , Octreótido/uso terapéutico , Glucemia , Método Doble Ciego , Síndrome de Vaciamiento Rápido/metabolismo , Síndrome de Vaciamiento Rápido/fisiopatología , Femenino , Gastrectomía/efectos adversos , Hematócrito , Humanos , Insulina/sangre , Masculino , Concentración Osmolar , Pulso Arterial
20.
J Pain Symptom Manage ; 8(4): 196-200, 1993 May.
Artículo en Inglés | MEDLINE | ID: mdl-7963760

RESUMEN

To define changes in sleep and subjective fatigue associated with localized radiation treatment, and to determine their relationship to interleukin-1B (IL-1), we prospectively followed 15 men, none of whom were depressed during 8 wk of radiation treatment for localized prostate cancer. Each patient rated fatigue daily on a visual analogue scale, recorded hours slept, and completed the Beck Depression Inventory weekly. Serum IL-1, taken at baseline and Fridays, was measured by quantitative enzyme immunoassay. Ranked weekly mean fatigue scores for each subject increased at week 4 (mean, 17 fractions, 1.8 Gy) then plateaued and rose in weeks 6 and 7. In week 6, the last week of full volume radiation, subjects slept most compared to all other weeks including week 7 when treatment was coned down. Ranked serum IL-1 tended to rise between weeks 1 and 4, as fatigue scores rose. These data suggest that localized radiation treatment is associated with increased fatigue and sleep requirement independent of depressive symptoms. Relative serum IL-1 changes may be one signal for the systemic reaction and subjective fatigue associated with the acute effects of radiation.


Asunto(s)
Fatiga/etiología , Interleucina-1/efectos de la radiación , Neoplasias de la Próstata/radioterapia , Anciano , Anciano de 80 o más Años , Humanos , Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/complicaciones , Radioterapia/efectos adversos , Radioterapia/métodos
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