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1.
Healthcare (Basel) ; 12(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38275545

RESUMEN

Autistic adults experience challenges in maintaining employment; however, little is known about patterns of competitive employment through late midlife. This longitudinal study examined the change in hours of competitive employment for a cohort of autistic adults over a 22-year period. The study's aims were to provide a fine-grained analysis of competitive employment patterns, to determine whether there was age-related change, and to test whether trajectories differed between those with and without intellectual disability (ID). Using an accelerated longitudinal design, trajectories of hours of competitive employment were estimated from young adulthood through late midlife in a community-based cohort (n = 341; 1327 observations). Results indicated a significant curvilinear trajectory of age-related change in hours of competitive employment, with differences between those with and without ID. For those without ID, the number of competitive employment hours increased from young adulthood until early midlife, then leveled off and decreased into late midlife. For those with ID, engagement in competitive employment was low throughout. Although competitive employment is just one option for vocational engagement, it is a goal often articulated by autistic adults who seek entry into the general workforce. The present research reveals their degree of engagement in the competitive workforce across the decades of adulthood.

2.
Disabil Health J ; 17(2): 101545, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37980230

RESUMEN

BACKGROUND: Adults with intellectual and developmental disabilities (IDD) experienced significant disruptions in their access to health care, support services, and essential daily activities such as work, leisure, and routine daily care during COVID-19. OBJECTIVE: The purpose of this study was to describe overall experiences related to COVID-19 among adults with IDD, including the vaccination process, quality of life (QoL), and service satisfaction before and during the pandemic. METHODS: A longitudinal statewide survey of adults with IDD receiving long-term care support using a combination of self- and care partner report was completed prior to (2017; n = 331) and during (2021; n = 206) the pandemic. RESULTS: Qualitative results identified specific vaccine barriers, vaccine decision influencers, and general experiences during COVID-19 for adults with IDD. The importance of support staff, vaccine availability, disruption in daily activities, social context, and mental health implications were noted in responses to all three topics. Quantitative results showed lower QoL during COVID-19 (M = 2.99 vs. 3.14, p = .028); however, when reporter (self vs. care partner) and age were added to the model, differences between pre-vs. during-COVID were no longer significant. No significant differences in satisfaction of services were noted pre-vs. during-COVID-19. Ninety-six percent of respondents reported access to the vaccine, and 16 % experienced barriers getting the vaccine. QoL was associated with receiving the COVID-19 vaccine (r = 0.15, p = .036), level of agreement that the vaccine is safe (r = 0.17, p = .024), and level of agreement that getting the vaccine will help protect other vulnerable people in the community (r = .25, p = .001). Level of satisfaction with quality of services was also associated with level of agreement that the vaccine is safe (r = 0.15, p = .048). CONCLUSIONS: Overall, a better understanding of service continuation, support practices, and experiences related to COVID-19 will prepare us for future environmental and health crises by identifying areas for improvement, intervention, and policy change to meet the ongoing needs of adults with IDD.


Asunto(s)
COVID-19 , Personas con Discapacidad , Discapacidad Intelectual , Adulto , Niño , Humanos , Calidad de Vida , Vacunas contra la COVID-19 , Discapacidades del Desarrollo/psicología , Personas con Discapacidad/psicología , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/psicología
3.
Am J Intellect Dev Disabil ; 129(1): 26-40, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38147887

RESUMEN

Autistic individuals and their families are at risk for poor outcomes in employment and mental health and may be vulnerable to long-term effects of broader societal conditions. The aim of the current longitudinal study was to understand the impact of the Great Recession of 2007-2009 on autistic individuals and their mothers (N = 392). Hierarchical linear modeling (HLM) results indicated that problem behavior of autistic adults increased in the years following the recession. The rate at which autistic individuals moved away and lived separately from their mothers also slowed during the recession. Mothers experienced significantly higher levels of depressive symptoms postrecession, compared to prerecession. In many other respects, the autistic individuals and their mothers did not experience negative outcomes, suggesting resilience and a strong safety net. These included the physical health and vocational/employment status of the autistic adults and their mothers. Results point to specific areas of vulnerability of autistic individuals and their mothers during the economic downturn, as well as a broad pattern of resilience in these families.


Asunto(s)
Trastorno Autístico , Adulto , Femenino , Humanos , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Estudios Longitudinales , Madres/psicología , Salud Mental , Empleo
4.
PLoS One ; 18(9): e0291364, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37698999

RESUMEN

INTRODUCTION: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem chronic disease estimated to affect 836,000-2.5 million individuals in the United States. Persons with ME/CFS have a substantial reduction in their ability to engage in pre-illness levels of activity. Multiple symptoms include profound fatigue, post-exertional malaise, unrefreshing sleep, cognitive impairment, orthostatic intolerance, pain, and other symptoms persisting for more than 6 months. Diagnosis is challenging due to fluctuating and complex symptoms. ME/CFS Common Data Elements (CDEs) were identified in the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) Common Data Element Repository. This study reviewed ME/CFS CDEs item content. METHODS: Inclusion criteria for CDEs (measures recommended for ME/CFS) analysis: 1) assesses symptoms; 2) developed for adults; 3) appropriate for patient reported outcome measure (PROM); 4) does not use visual or pictographic responses. Team members independently reviewed CDEs item content using the World Health Organization International Classification of Functioning, Disability and Health (ICF) framework to link meaningful concepts. RESULTS: 119 ME/CFS CDEs (measures) were reviewed and 38 met inclusion criteria, yielding 944 items linked to 1503 ICF meaningful concepts. Most concepts linked to ICF Body Functions component (b-codes; n = 1107, 73.65%) as follows: Fatiguability (n = 220, 14.64%), Energy Level (n = 166, 11.04%), Sleep Functions (n = 137, 9.12%), Emotional Functions (n = 131, 8.72%) and Pain (n = 120, 7.98%). Activities and Participation concepts (d codes) accounted for a smaller percentage of codes (n = 385, 25.62%). Most d codes were linked to the Mobility category (n = 69, 4.59%) and few items linked to Environmental Factors (e codes; n = 11, 0.73%). DISCUSSION: Relatively few items assess the impact of ME/CFS symptoms on Activities and Participation. Findings support development of ME/CFS-specific PROMs, including items that assess activity limitations and participation restrictions. Development of psychometrically-sound, symptom-based item banks administered as computerized adaptive tests can provide robust assessments to assist primary care providers in the diagnosis and care of patients with ME/CFS.


Asunto(s)
Disfunción Cognitiva , Síndrome de Fatiga Crónica , Adulto , Humanos , Síndrome de Fatiga Crónica/diagnóstico , Elementos de Datos Comunes , Fatiga , Dolor
6.
J Autism Dev Disord ; 53(6): 2373-2383, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35325339

RESUMEN

Autistic youth are at risk for internalizing mental health problems such as depression and anxiety. Similarly, parents of autistic youth report higher levels of depression than parents of typically developing children. The goal of this study was to examine bidirectional associations between parent depression symptoms and the internalizing problems of autistic youth in 188 families across four time points (T1-T4; spaced 12 months apart). A cross-lagged panel model revealed that mother (T1 and T2) and father (T1) depression symptoms positively predicted the youth's internalizing problems 12 months later. The youth's internalizing problems at T3 positively predicted maternal depression symptoms at T4. Future research should explore genetic and environmental pathways that link parent depression and internalizing problems in autistic youth.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Femenino , Adolescente , Humanos , Niño , Depresión/epidemiología , Depresión/psicología , Salud Mental , Padres/psicología
7.
J Autism Dev Disord ; 52(11): 4908-4920, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34797470

RESUMEN

Over the past 10 years, identification of Autism Spectrum Disorder (ASD) risk has dramatically increased due to the wide-spread implementation of screening programs; yet, there is limited understanding about parent perceptions and experiences during the time period when risk is identified, but prior to receiving a formal diagnosis-a period that can last months to years given the long wait-lists for formal ASD evaluations. The current study aimed to examine parent perceptions of family impact (i.e., the impact their child's behaviors have on the family) between the time of risk-identification and formal diagnosis among 277 children identified as at-risk for ASD through screening positive in primary care. We aimed to compare family impact among those whose child met diagnostic criteria for ASD and those who did not. Parents of children who received a non-ASD diagnosis reported a higher baseline level of family impact (F[1, 274] = 5.82, p = .017); however, perceived difficult child behavior was a stronger predictor of family impact (t[6] = 13.11, p < .001) than later diagnostic group (t[6] = - 2.10, p = .037), and child functioning did not predict family impact (t[6] = -0.31, p = .76). These results suggest that in this population, perceived difficult child behavior is a stronger predictor of family impact than later diagnostic category and should be considered an important factor in family support.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Niño , Conducta Infantil , Familia , Humanos , Padres
8.
Autism ; 25(6): 1694-1708, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33908306

RESUMEN

LAY ABSTRACT: Little is known about parent experiences throughout the diagnostic process for autism or how these parent experiences may help explain the disparities that exist between Hispanic and non-Hispanic families in time-to-diagnosis among children identified as at risk for autism. The current study examined trajectories of parenting stress, coping, and perceived family impact over time, throughout the autism diagnostic process among Hispanic and non-Hispanic families. Hispanic families reported lower levels of parenting stress, coping, and negative family impact across time. Further, there were differences in the change in use of coping and the amount of negative family impact reported between Hispanic and non-Hispanic parents over time. These differences shed light on the unique experiences and strengths of Hispanic families demonstrate. Interventions that leverage those strengths and focus on education, empowerment, and resilience might be particularly beneficial for Hispanic families and may also better inform work to increase resilience.


Asunto(s)
Trastorno del Espectro Autista , Adaptación Psicológica , Niño , Humanos , Responsabilidad Parental , Padres , Estrés Psicológico
9.
J Autism Dev Disord ; 51(10): 3432-3442, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33387245

RESUMEN

Parents of children with autism spectrum disorder (ASD) show increased levels of parenting stress, but only one study has examined this association before a diagnostic evaluation. We conducted a cross-sectional study of parenting stress in 317 low SES parents with children at-risk for ASD before a diagnostic evaluation. Multiple regression modeling evaluated the associations between parenting stress and parent and child factors. Parenting stress was negatively associated with social support and positively associated with active avoidance coping and parental worry. However, parenting stress was not associated with the child's ASD symptom severity or adaptive functioning, except for self-direction. Findings suggest parenting stress among parents of children at risk of ASD should be assessed prior to diagnosis.


Asunto(s)
Trastorno del Espectro Autista , Responsabilidad Parental , Trastorno del Espectro Autista/diagnóstico , Niño , Estudios Transversales , Humanos , Padres , Estrés Psicológico/diagnóstico
10.
J Abnorm Child Psychol ; 48(6): 865-879, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32170525

RESUMEN

Family research in the field of ASD has focused on describing the impact of child challenges on parents, usually mothers, and given little attention to the ways in which mothers and fathers reciprocally influence the development of the child with ASD. The current study examined the direction of effects between the emotional quality of the mother-child and father-child relationships and the child's severity of ASD symptoms and emotional and behavioral problems across three time points spanning 2 years. Using parent Five Minute Speech Samples and teacher ratings of the severity of the child's ASD symptoms and emotional and behavioral problems, four cross-lagged structural equation models were employed to test bidirectional effects between parent warmth and criticism and child ASD symptoms and emotional and behavioral problems across three waves of data (approximately 12 months apart) in 159 families who had a child with ASD (initially aged 6 to 13 years). Mothers and fathers had an average age of 39.53 (SD=5.55) and 41.66 years (SD=6.19). Children with ASD were predominately male (86.2%) and white, non-Hispanic (76.7%). Crossed-lagged model results indicated bidirectional effects for both mothers and fathers. Warmth in the mother-child relationship and father-child relationship impacted child functioning at earlier time points. In the opposite direction, child functioning impacted father warmth and mother criticism at later time points. Findings indicate that the emotional quality of the parent-child relationships are bidirectionally related to the symptoms and emotional and behavioral problems of children with ASD. Important implications for supporting families are discussed.


Asunto(s)
Trastorno Autístico/psicología , Relaciones Padres-Hijo , Problema de Conducta/psicología , Adolescente , Adulto , Trastorno del Espectro Autista/psicología , Niño , Preescolar , Emociones , Relaciones Padre-Hijo , Padre/psicología , Femenino , Humanos , Masculino , Relaciones Madre-Hijo , Madres/psicología , Padres
11.
Fam Process ; 59(2): 636-650, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-30844091

RESUMEN

Parents of children with autism spectrum disorder (ASD) often report poor psychological well-being, including a high level of parenting stress and depressive symptoms. Little is known about the extent to which poor parent psychological well-being alters the emotional quality of the parent-child relationship in a context of child ASD. This study examined the association between actor (one's own) and partner (one's partner's) level of parenting stress and depressive symptoms and the emotional quality of the parent-child relationship using a Five Minute Speech Sample (FMSS) in 150 families of children with ASD, aged 5-12 years (85.7% male). Mothers and fathers were aged 38.69 (SD = 5.62) and 40.76 (SD = 6.19), respectively; 76% of mothers and 68% of fathers had a college degree. Structural equation modeling, using Analysis of Moment Structures software, was used to test Actor-Partner Interdependence Models. Results indicated that mother's level of parenting stress and depressive symptoms were associated with her own FMSS Warmth and Criticism toward the child with ASD 12 months later in negative and positive directions. Mother's level of parenting stress was also negatively associated with father's FMSS Warmth toward the child with ASD 12 months later. Finally, father's level of parenting stress was positively associated with his FMSS Criticism toward the child with ASD. Overall, findings indicate that the mother-child and father-child relationship are both impacted by parent psychological well-being in families of children with ASD; however, actor effects are stronger for mothers and partner effects were only found for fathers. Implications for interventions are discussed.


Los padres de los niños con trastorno del espectro autista (TEA) generalmente informan un bienestar psicológico deficiente, como un alto nivel de estrés por la crianza y síntomas depresivos. Se sabe muy poco acerca de la medida en la que el bienestar psicológico deficiente de los padres altera la calidad emocional de la relación entre padres e hijos en un contexto de TEA de los niños. El presente estudio analizó la asociación entre el nivel de estrés por la crianza y los síntomas depresivos del actor (los de uno) y de la pareja (la pareja de uno) y la calidad emocional de la relación entre padres e hijos usando una muestra del habla de cinco minutos (Five Minute Speech Sample, FMSS) en 150 familias de niños con TEA, de entre 5 y 12 años (85.7% masculino). Las madres y los padres tenían 38.69 (Desviación Típica = 5.62) y 40.76 (Desviación Típica = 6.19) de edad, respectivamente; el 76 % de las madres y el 68 % de los padres tenía un título universitario. Para evaluar los modelos de interdependencia actor-pareja se utilizaron los modelos de ecuaciones estructurales mediante el software de análisis de estructuras de momentos. Los resultados indicaron que el nivel de estrés por la crianza y los síntomas depresivos de la madre estuvieron asociados con su propia calidez y crítica según la FMSS hacia el niño con TEA doce meses después en direcciones negativas y positivas. El nivel de estrés por la crianza de la madre también estuvo asociado negativamente con la calidez del padre según la FMSS hacia el niño con TEA doce meses después. Finalmente, el nivel de estrés por la crianza del padre estuvo asociado positivamente con su crítica según la FMSS hacia el niño con TEA. En general, los resultados indican que la relación entre la madre y el niño y la relación entre el padre y el niño están ambas influidas por el bienestar psicológico de los padres en las familias de niños con TEA; sin embargo, los efectos del actor son más fuertes para las madres y solo se encontraron efectos de la pareja para los padres. Se debaten las implicancias para las intervenciones.


Asunto(s)
Trastorno del Espectro Autista/psicología , Relaciones Padres-Hijo , Responsabilidad Parental/psicología , Padres/psicología , Estrés Psicológico/psicología , Niño , Preescolar , Depresión/psicología , Emociones , Femenino , Humanos , Análisis de Clases Latentes , Masculino , Persona de Mediana Edad , Modelos Psicológicos
12.
J Autism Dev Disord ; 49(8): 3244-3256, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31077017

RESUMEN

Little research has examined family emotional climate in the context of having a child with autism spectrum disorder (ASD). The goal of the current study was to determine how the emotional quality of family subsystems (parent-child and parent couple relationships, for both mothers and fathers) combine to create various classes of family emotional climate and to identify predictors of class membership in 148 families of children with ASD. The emotional quality of family subsystems was assessed using Five Minute Speech Samples from mothers and fathers. In total, 148 families of children with ASD (86% male) aged 6-13 years were included in analyses. About one-third of parents did not have a college degree and more than two-thirds were of non-Hispanic White origin. Latent class analysis revealed that 43% of the sample was characterized by high levels of warmth and low levels of criticism in both the parent-child and parent couple relationships; 12% of the sample was characterized by low warmth and high criticism in both sets of relationships; and the rest of the sample was divided among three additional classes of emotional climate characterized by different configurations of warmth and criticism across both sets of relationships. Parent level of broader autism phenotype and child emotional and behavioral problems were associated with emotional climate class membership. Implications for interventions are discussed.


Asunto(s)
Trastorno del Espectro Autista/psicología , Emociones , Familia/psicología , Relaciones Padres-Hijo , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Problema de Conducta
13.
Autism ; 23(8): 2068-2079, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30995078

RESUMEN

The broader autism phenotype refers to sub-clinical autism spectrum disorder characteristics involving socially and emotionally aloof and rigid personality traits and social communication difficulties. Relatives of individuals with autism spectrum disorder, including parents, evidence an increased rate of broader autism phenotype. The goal of this study was to evaluate the association between actor (one's own) and partner (their partner's) broader autism phenotype and the self-reported, observed, and physiological (i.e. electrodermal reactivity) markers of the quality of videotaped couple problem-solving interactions in 158 couples, who had a child with autism spectrum disorder (aged 5-12 years). The mean age of mothers was 39.79 (standard deviation = 5.06) years and the mean age of fathers was 41.77 (standard deviation = 6.02) years for fathers, and 36.6% of parents did not have a college degree. Actor-partner interdependence models, using structural equation modeling in analysis of moment structures, were conducted. Results indicated that parent broader autism phenotype was positively related to adverse couple problem-solving interactions across all measurement methods (observed codes, self-reported affect, and electrodermal reactivity). These effects were independent of child-related challenges. The effect of parent broader autism phenotype occurred through both actor and partner pathways and was strongest for father broader autism phenotype.


Asunto(s)
Trastorno del Espectro Autista , Conflicto Familiar/psicología , Padres/psicología , Solución de Problemas , Adulto , Relaciones Familiares , Femenino , Respuesta Galvánica de la Piel , Humanos , Masculino , Persona de Mediana Edad , Fenotipo
14.
Autism ; 22(4): 469-478, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28326797

RESUMEN

When faced with child-related challenges associated with autism spectrum disorder, positive and negative social exchanges may be critical to parents' psychological well-being. This study examined the types and sources of positive and negative social exchanges reported by mothers and fathers of children with autism spectrum disorder and their association with parental depressive symptoms in 176 families of children (5-12 years; 85% male) with autism spectrum disorder. One-way repeated measure multivariate analyses of variance and multilevel modeling were used. Results indicated that informational was the most frequent type, and one's spouse was the primary source, of both positive and negative social exchanges. Fathers reported fewer positive, and also fewer negative, social exchanges with family, friends, and health professionals than mothers. Positive and negative social exchanges with one's spouse were most strongly associated with depressive symptoms. Findings have implications for interventions designed to foster optimal outcomes in families of children with autism spectrum disorder.


Asunto(s)
Trastorno del Espectro Autista/psicología , Padre/psicología , Relaciones Interpersonales , Madres/psicología , Adulto , Niño , Preescolar , Familia/psicología , Femenino , Amigos/psicología , Personal de Salud/psicología , Humanos , Masculino
15.
J Child Fam Stud ; 26(8): 2152-2165, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29097880

RESUMEN

We compared the couple conflict of parents of children with autism spectrum disorder (ASD) to a comparison group of parents of children without disabilities using self-reported and observational measures. In total, 178 couples who had a child with ASD (aged 5-12 years) and 174 couples who had children without disabilities (aged 5-12 years), recruited from a Midwestern state in the United States, reported on couple conflict in everyday life and engaged in an observed couple conflict interaction. Parents of children with ASD reported more frequent, severe, and unresolved couple problems than the comparison group. Parents who had a child with ASD were observed to have less engaged, balanced, and cooperative couple conflict interactions, but demonstrated more positive affect and sensitivity towards one another, than parents in the comparison group. Group differences had small effect sizes. Findings have implications for marital therapy and relationship education programs.

16.
J Med Primatol ; 40(5): 342-50, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21950722

RESUMEN

BACKGROUND: Successful transurethral bladder catheterization in male non-human primates can be challenging. An optimized approach for consistent and reproducible catheterization using a refined technique is described. METHODS: Under sedated and non-sedated conditions, transurethral bladder catheterization was performed on 25 male rhesus macaques of varying ages and body weights over time. A refined technique ensuring optimal lubrication of the urethral canal prior to catheter insertion was utilized along with various single and multiple lumen catheters. RESULTS: All animals were successfully catheterized. Sixty-five catheterization sessions were conducted with a high overall success rate (100%). The incidence of catheter (10%) and post-catheterization (2%) complications was low. CONCLUSIONS: The urinary bladder of male rhesus can be reliably and reproducibly catheterized with minimal complication using this approach. Successful catheterization was facilitated by thorough urethral lubrication and using suitable catheters. In addition, this approach may be performed without sedation on thoroughly conditioned animals.


Asunto(s)
Sedación Consciente/veterinaria , Macaca mulatta/cirugía , Vejiga Urinaria/cirugía , Cateterismo Urinario/métodos , Animales , Masculino , Reproducibilidad de los Resultados , Cateterismo Urinario/instrumentación
17.
J Pharmacol Exp Ther ; 338(1): 220-7, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21459965

RESUMEN

Both the physiological role of muscarinic receptors for bladder function and the therapeutic efficacy of antimuscarinic agents for overactive bladder syndrome are well documented. We investigated the effect of antimuscarinic agents with different subtype selectivity on urodynamic parameters in nonhuman primates and rodents and compared plasma levels of these agents between species. Anesthetized rhesus monkeys were transurethrally catheterized, and the bladder was infused with saline. Urodynamic parameters were measured before and after intravenous drug administration. Tolterodine (nonselective) and oxybutynin (moderately M(3)-selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M(3)-selective) were needed to increase the bladder capacity than those needed to decrease the micturition pressure. In rats, tolterodine had no effect on the bladder capacity but decreased the micturition pressure at all of the doses administered. Oxybutynin also decreased micturition pressure and increased bladder capacity at the highest dose. Plasma levels of these drugs overlap in both species. These results suggest that, in addition to the M(3) receptor, other muscarinic receptor subtypes contribute to regulate bladder storage function in nonhuman primates, since less subtype-selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure compared with M(3)-selective darifenacin. In addition, the role of muscarinic receptors in bladder storage function varies between primates and rodents. Compared with rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.


Asunto(s)
Antagonistas Muscarínicos/farmacología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiología , Animales , Compuestos de Bencidrilo/farmacología , Cresoles/farmacología , Femenino , Macaca mulatta , Ácidos Mandélicos/farmacología , Fenilpropanolamina/farmacología , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie , Tartrato de Tolterodina
18.
Bioorg Med Chem Lett ; 19(13): 3531-5, 2009 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-19447613

RESUMEN

Novel water-soluble amide analogs were synthesized from nocathiacin I (1) through the formation of the carboxylic acid intermediate followed by coupling to primary or secondary amines. Several compounds with potent antibacterial activity and adequate water solubility were identified. Of these, compound 19 was selected for more extensive evaluation because of its excellent in vitro antibacterial activity and in vivo efficacy, as well as clean off-target screening.


Asunto(s)
Amidas/química , Antibacterianos/síntesis química , Péptidos/química , Piperazinas/síntesis química , Amidas/síntesis química , Animales , Antibacterianos/química , Antibacterianos/farmacología , Péptidos y Proteínas de Señalización Intercelular , Ratones , Pruebas de Sensibilidad Microbiana , Piperazinas/química , Piperazinas/farmacocinética , Solubilidad , Relación Estructura-Actividad , Agua/química
19.
J Am Chem Soc ; 130(36): 12102-10, 2008 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-18698773

RESUMEN

Bacterial resistance to antibiotics, particularly to multiple drug resistant antibiotics, is becoming cause for significant concern. The only really viable course of action is to discover new antibiotics with novel mode of actions. Thiazolyl peptides are a class of natural products that are architecturally complex potent antibiotics but generally suffer from poor solubility and pharmaceutical properties. To discover new thiazolyl peptides potentially with better desired properties, we designed a highly specific assay with a pair of thiazomycin sensitive and resistant strains of Staphylococcus aureus, which led to the discovery of philipimycin, a new thiazolyl peptide glycoside. It was isolated along with an acid-catalyzed degradation product by bioassay-guided fractionation. Structure of both compounds was elucidated by extensive application of 2D NMR, 1D TOCSY, and HRESIFT-MS/MS. Both compounds showed strong antibacterial activities against gram-positive bacteria including MRSA and exhibited MIC values ranging from 0.015 to 1 microg/mL. Philipimycin was significantly more potent than the degradation product. Both compounds showed selective inhibition of protein synthesis, indicating that they targeted the ribosome. Philipimycin was effective in vivo in a mouse model of S. aureus infection exhibiting an ED50 value of 8.4 mg/kg. The docking studies of philipimycin suggested that a part of the molecule interacts with the ribosome and another part with Pro23, Pro22, and Pro26 of L11 protein, which helped in explaining the differential of activities between the sensitive and resistant strains. The design and execution of the bioassay, the isolation, structure, in vitro and in vivo antibacterial activity, and docking studies of philipimycin and its degradation product are described.


Asunto(s)
Antibacterianos/química , Proteínas Bacterianas/química , Micromonosporaceae/química , Tiazoles/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/farmacología , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Péptidos Cíclicos/farmacología , Espectrometría de Masa por Ionización de Electrospray , Staphylococcus aureus/efectos de los fármacos , Tiazoles/aislamiento & purificación , Tiazoles/farmacología
20.
Antimicrob Agents Chemother ; 51(9): 3434-6, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17606686

RESUMEN

A novel oxazolidinone, AM 7359, was evaluated in two mouse models of Staphylococcus aureus infection. AM 7359 and linezolid were equally efficacious in a methicillin-susceptible S. aureus organ burden model and a methicillin-resistant S. aureus localized infection model. However, AM 7359 was eightfold more efficacious than linezolid against a linezolid- and methicillin-resistant S. aureus strain in this localized (thigh) infection model.


Asunto(s)
Antibacterianos/uso terapéutico , Oxazolidinonas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Acetamidas/uso terapéutico , Administración Oral , Animales , Recuento de Colonia Microbiana , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Linezolid , Resistencia a la Meticilina , Ratones , Ratones Endogámicos C3H , Infecciones Estafilocócicas/microbiología
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