RESUMEN
Bone degenerative diseases are on the increase globally and are often problematic to treat. This has led to a demand to identify supplements that aid bone growth and formation. Aquamin is a natural multi-mineral food supplement, derived from the red algae Lithothamnion species which contains calcium, magnesium and 72 other trace minerals. It has been previously reported to increase bone formation and mineralisation. This study aimed to investigate the 28 day in vitro osteogenic response of Aquamin supplemented with Vitamin D. The osteogenic potential of MC3T3-E1 osteoblast-like cells was analysed in standard osteogenic medium supplemented with Aquamin +/- Vitamin D3, and the controls consisted of osteogenic medium, +/- Vitamin D3. Proliferation of osteoblasts, metabolic activity and cell viability did not differ between Aquamin and the osteogenic control groups. Alkaline phosphatase (ALP) levels and mineralisation were increased by the supplementation of Aquamin, and the addition of Vitamin D3 increased mineralisation for all groups. The combination of Aquamin and Vitamin D3 yielded a significant increase in ALP and mineralisation over Aquamin alone and the standard osteogenic control +/- Vitamin D3. This study demonstrates that Aquamin aids osteogenesis, and that its osteogenic response can be enhanced by combining Aquamin with Vitamin D3.
Asunto(s)
Suplementos Dietéticos , Minerales/farmacología , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Vitamina D/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Línea Celular , Supervivencia Celular , Ratones , Rhodophyta/químicaRESUMEN
Growing pigs can display undesirable behaviours, reflecting or causing poor welfare. Addition of magnesium (Mg) to the diet could reduce these, as Mg supplementation has been associated with improved coping ability in response to stress. This study examined the effect of supplementation with a Mg-rich marine extract-based product (Supplement) on the behaviour, skin and tail lesion scores and salivary cortisol concentrations of growing pigs. At weaning (28 days), 448 piglets were assigned to either Control or Supplement (0.05%) diets in single-sex groups of 14. Four weeks later (c. 17 kg), pigs were blocked according to weight and back test scores. Seven piglets from each pen were mixed with seven from another pen of the same sex and dietary treatment to yield the following groups: control male, Supplement male, control female and Supplement female (n = 4 of each). This marked the start of the 9-week experimental period. Instances of the following behaviours were recorded in each pen for 8 × 2 min periods 1 day/week: aggression (fight, head-knock and bite); harmful (tail-in-mouth, ear-chewing and belly-nosing); and sexual/mounting behaviour. Four focal pigs were selected from each pen, and their behaviour was continuously recorded for 2 × 5 min periods on the same day. Saliva was collected once per week at 1000 h by allowing pigs to chew on a cotton bud for c. 1 min. Salivary cortisol was analysed in duplicate by an enzyme immunoassay. Skin and tail lesions were scored according to severity 1 day/week. There were fewer aggressive incidents in Supplement pens (P < 0.01), and mounting behaviour (performed only by males) was almost three times lower in Supplement than in control pens (P < 0.01). However, there was no effect of Supplement on the incidence of each of the harmful behaviours. Behaviour of the focal pigs showed no treatment effect on the duration or incidence of aggressive behaviour. However, Supplement pigs spent less time performing harmful behaviours compared with control pigs (P < 0.001). Supplement had no effect on the occurrence or severity of tail-biting outbreaks or on tail lesion scores. However, Supplement females had lower skin lesion scores, in particular in the ears and shoulders (P < 0.01). Finally, Supplement pigs had lower salivary cortisol concentrations (P < 0.01). Mounting is a major welfare concern in uncastrated pigs, and therefore this represents an important welfare benefit of Supplement. Reduced salivary cortisol, in conjunction with reduced skin lesion scores in supplemented females, suggests that addition of a Mg-rich marine extract improved pig welfare in this system.
Asunto(s)
Conducta Animal/efectos de los fármacos , Suplementos Dietéticos , Hidrocortisona/análisis , Magnesio/farmacología , Saliva/química , Porcinos/crecimiento & desarrollo , Agresión/efectos de los fármacos , Animales , Mordeduras y Picaduras/patología , Estudios de Casos y Controles , Femenino , Técnicas para Inmunoenzimas/veterinaria , Masculino , ObservaciónRESUMEN
School-based curricula have become a mainstay of drug prevention policy in the United States and are increasing in popularity in other parts of the world. The promotion and dissemination of these interventions has been driven in large part by the creation of lists of programmes which, it is claimed, are grounded in scientific evidence demonstrating their effectiveness. Recently concerns have been raised about the data analysis and presentation practices used in evaluations of a number of programmes that appear on these lists. Here we examine a series of papers from an evaluation of an intervention that combined the Strengthening Families Program 10-14 and Life Skills Training Program, each of which is among the most widely advocated universal drug prevention programmes. The data analysis and presentation practices employed in the evaluation of this combined programme include one-tailed significance testing, alpha levels of 0.10, changes in outcome variables across publications and use of the post-test data as the baseline when assessing change over time. Taken together, these practices severely limit the claims that can be made about the results presented in the evaluation. Specifically, we believe that far from supporting the evaluators' claims concerning the rigour of the findings and their generalisability and public health significance, the results are very fragile, of little practical significance and quite possibly analysis-dependent.
Asunto(s)
Trastornos Relacionados con Alcohol/prevención & control , Promoción de la Salud/métodos , Trastornos Relacionados con Sustancias/prevención & control , Medicina Basada en la Evidencia/métodos , Salud de la Familia , Educación en Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Evaluación de Programas y Proyectos de Salud , Instituciones Académicas , Estados UnidosRESUMEN
AIMS: The purpose of the present study was to assess the effects on alcohol-involved traffic crashes and fatalities of the 0.08 blood alcohol concentration (BAC) per se law introduced in the state of Texas in 1999. METHOD: Data pertaining to alcohol-involved traffic crashes and fatalities were extracted from two datasets: the Fatality Analysis Reporting System (FARS) compiled by the National Highway Traffic Safety Administration (for the period January 1995-September 2002), and the Texas Department of Public Safety (DPS) reports of Alcohol Related Motor Vehicle Traffic Accidents and Casualties (for the period January 1995-December 2000). The data were analysed using time-series methods (ARIMA routines). The effects of the law on all drivers were assessed, along with the effects among gender, racial, and age subgroups and crash location (urban vs rural). RESULTS: Separate time-series analyses were conducted with all alcohol-involved and fatal alcohol-involved crashes from the DPS dataset and fatal alcohol-involved crashes from the FARS dataset as the outcome variables. None of the effects for either the total sample or any of the subgroups analysed was statistically significant (this was true of both the FARS and DPS datasets). CONCLUSIONS: While there is a growing body of evidence that indicates that 0.08 BAC laws can be effective in reducing alcohol-involved traffic accidents and fatalities, the present study shows that this was not the case in Texas. Future research should move beyond the simple question of whether or not 0.08 BAC laws 'work' and instead explore in more detail the conditions, such as publicity and enforcement, under which the law does or does not contribute to a decline in alcohol-involved accidents and fatalities.
Asunto(s)
Accidentes de Tránsito/legislación & jurisprudencia , Accidentes de Tránsito/estadística & datos numéricos , Consumo de Bebidas Alcohólicas/epidemiología , Conducción de Automóvil/legislación & jurisprudencia , Conducción de Automóvil/estadística & datos numéricos , Accidentes de Tránsito/mortalidad , Adulto , Consumo de Bebidas Alcohólicas/sangre , Etanol/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Texas/epidemiología , Población Urbana/estadística & datos numéricosRESUMEN
Ecological studies have shown a relationship between alcohol outlet densities and violence and between the location of crimes related to illicit drug use (so-called 'hot spots') and violence. To date, no study has compared the effects of alcohol outlets and drug hot spots on rates of violence. The present study examined this relationship in the City of Houston, Texas. An ecological study design was employed, using a sample of 439 census tracts from Houston, Texas. Neighborhood socio-structural, alcohol outlet density, drug crime density and violent crime density data were collected from archival sources and analyzed using multivariate and spatial statistics. Using ordinary least-squares analysis, the neighborhood socio-structural covariates explained about 40% of the variability in violent crime. Adding alcohol outlet density in the target census tracts explained an additional 6%, while the addition of drug crime density explained an additional 32%. In the final model, that controlled for the effects of autocorrelated error, both drug crime density in the target and adjacent census tracts remained significant predictors of violent crime, while only off-sale density in the target census tract remained significant in the model. The findings indicate that drug crime density explained a greater amount of variance in violent crime rates than the alcohol outlet density. The methodological and policy implications of these findings are discussed, along with the shortcomings of the analysis presented.
Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas/estadística & datos numéricos , Mercadotecnía , Características de la Residencia , Violencia/estadística & datos numéricos , Crimen/estadística & datos numéricos , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Mercadotecnía/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Texas/epidemiología , Población UrbanaRESUMEN
The approach described in this article is premised on the idea that drug and alcohol use-related problems are heterogeneously distributed with respect to population and geography, and therefore, are essentially local problems. More specifically, it is argued that viewing a local community as an interacting set of systems that support or buffer the occurrence of specific substance misuse outcomes, opens up to research two important prospects. The first of these involves creating adequate systems models that can capture the primary community structures and relationships that support public health problems such as alcohol and drug misuse and related outcomes. The second entails rationally testing control strategies that have the potential to moderate or reduce these problems. Understanding and controlling complex dynamic systems models nowadays pervades all scientific disciplines, and it is to research in areas such as biology, ecology, engineering, computer sciences, and mathematics that researchers in the field of addictions must turn to in order to better study the complexity that confronts them as they try to understand and prevent problems resulting from alcohol and drug use and misuse. Here we set out what such a systems-based understanding of alcohol- and drug use-related problems will require and discuss its implications for public policy and prevention programming.
Asunto(s)
Modelos Teóricos , Características de la Residencia , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicología , Humanos , Condiciones SocialesRESUMEN
AIMS: To examine the relationship between alcohol outlet density and violent crime controlling for neighbourhood sociostructural characteristics and the effects of spatially autocorrelated error. DESIGN: The sample for this ecologic study comprised 188 census tracts from the City of Austin, Texas and 263 tracts from the City of San Antonio, Texas. Data pertaining to neighbourhood social structure, alcohol density and violent crime were collected from archival sources, and analysed using bivariate, multivariate and geospatial analyses. RESULTS: Using ordinary least squares analysis, the neighbourhood sociostructural covariates explained close to 59% of the variability in violent crime rates in Austin and close to 39% in San Antonio. Adding alcohol outlet density in the target and adjacent census tracts improved the explanatory power of both models. Alcohol outlet density in the target census tract remained a significant predictor of violent crime rates in both cities when the effects of autocorrelated error were controlled for. In Austin, the effects of alcohol outlet density in the adjacent census tracts also remained significant. The final model explains 71% of the variance in violent crime in Austin and 56% in San Antonio. CONCLUSIONS: The findings show a clear association between alcohol outlet density and violence, and suggest that the issues of alcohol availability and access are fundamental to the prevention of alcohol-related problems within communities.
Asunto(s)
Bebidas Alcohólicas , Mercadotecnía , Características de la Residencia , Violencia , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas/economía , Bebidas Alcohólicas/estadística & datos numéricos , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Mercadotecnía/economía , Mercadotecnía/estadística & datos numéricos , Análisis Multivariante , Análisis de Regresión , Características de la Residencia/estadística & datos numéricos , Factores Socioeconómicos , Violencia/economía , Violencia/estadística & datos numéricosRESUMEN
This study profiles nursing home residents receiving alcohol and drug treatment, describing their sociodemographic, health, and treatment characteristics. We analyzed 3,662 admission assessments in the Minimum Data Set for people receiving alcohol/drug treatment from June, 1998 through September, 2000. These residents were likely to be male and under age 50. More than half were White and 29 percent were African American. Typically, these residents were not physically or cognitively impaired. However, more than 39 percent had unstable health patterns and almost 21 percent had HIV disease. Thirty-eight percent had a history of mental health conditions, with 24 percent having depression and almost 18 percent having schizophrenia. At least 75 percent received no psychological therapy in the previous 7 days and a majority did not receive antipsychotic, antianxiety, or antidepressant medications. These analyses indicate that most recently admitted residents receiving alcohol/drug treatment did not receive mental health therapy in nursing homes.
Asunto(s)
Trastornos del Conocimiento/epidemiología , Seropositividad para VIH/epidemiología , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Servicios de Salud Mental/provisión & distribución , Casas de Salud , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/rehabilitación , Actividades Cotidianas , Adulto , Alcoholismo/epidemiología , Alcoholismo/rehabilitación , Trastornos del Conocimiento/diagnóstico , Comorbilidad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: This study examined the relationship between neighborhood social structure, alcohol outlet densities and violent crime in Camden, New Jersey. METHOD: Data pertaining to neighborhood social structure, violent crime and alcohol density were collected for 98 block groups, and analyzed using bivariate, multivariate and spatial analyses. RESULTS: Each type of analysis showed that those areas with high alcohol outlet densities experienced more violent crime than low-density areas, after controlling for neighborhood social structure. In the multivariate regression analysis, alcohol outlet densities explained close to one fifth of the variability in violent crime rates across block groups--more than any one of the neighborhood structural variables included in the analysis. These findings were replicated in the spatial analysis, which also showed that alcohol outlet densities contributed significantly to violent crime within target block groups but not in adjacent block groups. CONCLUSIONS: High alcohol outlet density is associated with high rates of violent crime in this urban community. Spatial analysis suggests that alcohol outlets elevate the rate of violent crime within the immediate neighborhood context, not in surrounding neighborhoods.
Asunto(s)
Alcoholismo/epidemiología , Crimen/estadística & datos numéricos , Etanol , Violencia/estadística & datos numéricos , Adolescente , Niño , Procesos de Grupo , Humanos , Características de la ResidenciaRESUMEN
Increasing resistance to chemotherapeutic regimes remains a serious problem in the treatment of acute myeloid leukaemia. We have shown that phosphatidylinositol (PI) 3-kinase inhibition significantly sensitises the AML derived cell line, HL60 to chemotherapeutic drug- and Fas-induced apoptosis. PI3-kinase inhibition significantly potentiates cytotoxic drug-induced c-jun N-terminal kinase (JNK) activation, reported to be a requirement for apoptosis. However, JNK inhibition does not enhance cell viability following treatment with drug and inhibitor. Furthermore, PI3-kinase inhibition significantly increases sensitivity to apoptosis mediated by an exogenous receptor agonist, again by a JNK independent mechanism. These results suggest that PI3-kinase inhibitors could be of significant therapeutic importance, lowering the threshold for apoptosis induced by both chemotherapy and cell-mediated immune response.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Leucemia/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas , Receptor fas/biosíntesis , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales de Origen Murino , Activación Enzimática/efectos de los fármacos , Proteína Ligando Fas , Células HL-60 , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos , Glicoproteínas de Membrana/biosíntesis , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/genética , Fosforilación , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Transcripción Genética/efectos de los fármacos , Tretinoina/farmacologíaRESUMEN
p19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is a subunit of the recently discovered cytokine IL-23. Here we show that expression of p19 in multiple tissues of transgenic mice induced a striking phenotype characterized by runting, systemic inflammation, infertility, and death before 3 mo of age. Founder animals had infiltrates of lymphocytes and macrophages in skin, lung, liver, pancreas, and the digestive tract and were anemic. The serum concentrations of the proinflammatory cytokines TNF-alpha and IL-1 were elevated, and the number of circulating neutrophils was increased. In addition, ubiquitous expression of p19 resulted in constitutive expression of acute phase proteins in the liver. Surprisingly, liver-specific expression of p19 failed to reproduce any of these abnormalities, suggesting specific requirements for production of biologically active p19. Bone marrow transfer experiments showed that expression of p19 by hemopoietic cells alone recapitulated the phenotype induced by its widespread expression, pointing to hemopoietic cells as the source of biologically active p19. These findings indicate that p19 shares biological properties with IL-6, IL-12, and G-CSF and that cell-specific expression is required for its biological activity.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/inmunología , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/mortalidad , Infertilidad/genética , Infertilidad/mortalidad , Interleucinas/biosíntesis , Interleucinas/genética , Transgenes/inmunología , Proteínas de Fase Aguda/biosíntesis , Proteínas de Fase Aguda/genética , Anemia/sangre , Anemia/genética , Anemia/inmunología , Animales , Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/patología , Pollos , Citocinas/biosíntesis , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Trastornos del Crecimiento/inmunología , Hematopoyesis Extramedular/genética , Hematopoyesis Extramedular/inmunología , Humanos , Infertilidad/inmunología , Inflamación/genética , Inflamación/inmunología , Inflamación/mortalidad , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interleucina-23 , Subunidad p19 de la Interleucina-23 , Interleucina-6/biosíntesis , Recuento de Leucocitos , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Transgénicos , Neutrófilos/patología , Especificidad de Órganos/genética , Especificidad de Órganos/inmunología , Fenotipo , ConejosRESUMEN
The sequence of a novel hemopoietic cytokine was discovered in a computational screen of genomic databases, and its homology to mouse thymic stromal lymphopoietin (TSLP) suggests that it is the human orthologue. Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R alpha-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. Human TSLPR and IL-7Ralpha are principally coexpressed on monocytes and dendritic cell populations and to a much lesser extent on various lymphoid cells. In accord, we find that human TSLP functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells, as evidenced by the strong induction of the costimulatory molecules CD40 and CD80 and the enhanced capacity to elicit proliferation of naive T cells.
Asunto(s)
Citocinas/fisiología , Células Mieloides/metabolismo , Timo/fisiología , Secuencia de Aminoácidos , Animales , Línea Celular , Separación Celular , Células Cultivadas , Quimiocina CCL17 , Quimiocinas CC/biosíntesis , Biología Computacional , Citocinas/análisis , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Humanos , Integrina alfaXbeta2/biosíntesis , Interleucina-7/metabolismo , Interleucina-7/fisiología , Sustancias Macromoleculares , Ratones , Datos de Secuencia Molecular , Monocitos/metabolismo , Células Mieloides/inmunología , Receptores de Citocinas/análisis , Receptores de Citocinas/biosíntesis , Receptores de Interleucina-7/biosíntesis , Células del Estroma/fisiología , Timo/citología , Linfopoyetina del Estroma TímicoRESUMEN
Drug resistance, to date, has primarily been attributed to increased drug export or detoxification mechanisms. Despite correlations between drug export and drug resistance, it is increasingly apparent that such mechanisms cannot fully account for chemoresistance in neoplasia. It is now widely accepted that chemotherapeutic drugs kill tumour cells by inducing apoptosis, a genetically regulated cell death programme. Evidence is emerging that the exploitation of survival pathways, which may have contributed to disease development in the first instance, may also be important in the development of the chemoresistance. This review discusses the components of and associations between multiple signalling cascades and their possible contribution to the development of neoplasia and the chemoresistant phenotype.
Asunto(s)
Apoptosis/fisiología , Transducción de Señal/fisiología , Animales , Resistencia a Medicamentos/fisiología , Humanos , Neoplasias/etiología , Neoplasias/patología , Neoplasias/fisiopatologíaRESUMEN
We have characterized a cytokine produced by Th2 cells, designated as IL-25. Infusion of mice with IL-25 induced IL-4, IL-5, and IL-13 gene expression. The induction of these cytokines resulted in Th2-like responses marked by increased serum IgE, IgG(1), and IgA levels, blood eosinophilia, and pathological changes in the lungs and digestive tract that included eosinophilic infiltrates, increased mucus production, and epithelial cell hyperplasia/hypertrophy. In addition, our studies show that IL-25 induces Th2-type cytokine production by accessory cells that are MHC class II(high), CD11c(dull), and lineage(-). These results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types.
Asunto(s)
Eosinofilia/inducido químicamente , Enfermedades Gastrointestinales/inducido químicamente , Regulación de la Expresión Génica/efectos de los fármacos , Sustancias de Crecimiento/aislamiento & purificación , Hipergammaglobulinemia/inducido químicamente , Interleucina-13/biosíntesis , Interleucina-4/biosíntesis , Interleucina-5/biosíntesis , Interleucinas , Subgrupos de Linfocitos T/efectos de los fármacos , Células Th2/metabolismo , Secuencia de Aminoácidos , Animales , Linaje de la Célula , Células Cultivadas , Clonación Molecular , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Eosinofilia/inmunología , Eosinofilia/patología , Mucosa Gástrica/patología , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/patología , Sustancias de Crecimiento/metabolismo , Sustancias de Crecimiento/farmacología , Sustancias de Crecimiento/toxicidad , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Hiperplasia , Hipertrofia , Integrina alfaXbeta2/análisis , Interleucina-13/genética , Interleucina-17 , Interleucina-4/genética , Interleucina-5/genética , Mucosa Intestinal/patología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Datos de Secuencia Molecular , Proteínas Nucleares , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/inmunología , Eosinofilia Pulmonar/patología , ARN Mensajero/biosíntesis , Receptores de Interleucina-4/deficiencia , Receptores de Interleucina-4/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Subgrupos de Linfocitos T/metabolismo , Células Th2/químicaRESUMEN
Drug resistance remains a serious limiting factor in the treatment of acute myeloid leukaemia (AML) either at initial presentation or following primary or subsequent relapses. Using specific kinase inhibitors, this study has investigated the contribution of the Ras/PI3-kinase regulated survival pathways to drug resistance and suppression of apoptosis in a cell line derived from AML (HL60). Inhibition of the Raf/MAP-kinase (ERK) pathway with a specific MAP-kinase inhibitor, apigenin did not sensitise HL60 cells to drug-induced apoptosis, indicating a lack of involvement in chemoresistance. In contrast, the PI3-kinase inhibitors, LY294002 and wortmannin, did induce a significant increase in apoptosis in combination with cytotoxic drugs. The contribution of downstream mediators of PI3-kinase, p70S6-kinase and PKB/Akt were then investigated. While inhibition of p70S6-kinase with rapamycin did not increase drug-induced apoptosis, PI3-kinase inhibition resulted in notable dephosphorylation of PKB, suggesting that the PI3-kinase/PKB survival pathway may play a major role in chemoresistance in AML. This pathway has been reported to mediate heterodimer interactions with the proapoptotic regulator, Bad. In contrast to previous studies, we found no evidence of Bad binding to anti-apoptotic Bcl-2, Bcl-XL or McI-1, or of alterations in Bax heterodimers. This suggests that alternative targets of PI3-kinase/PKB, distinct from the Bcl-2 family may be responsible for contributing to survival factor-mediated drug resistance in AML.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Células HL-60/efectos de los fármacos , Proteínas de Neoplasias/genética , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas , Androstadienos/farmacología , Apigenina , Camptotecina/farmacología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Supervivencia Celular , Cromonas/farmacología , Cicloheximida/farmacología , Dactinomicina/farmacología , Dimerización , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Etopósido/farmacología , Flavonoides/farmacología , Genes bcl-2 , Células HL-60/enzimología , Células HL-60/patología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Mitoxantrona/farmacología , Morfolinas/farmacología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Proteínas de Neoplasias/metabolismo , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Sirolimus/farmacología , Wortmanina , Proteína Letal Asociada a bcl , Proteína bcl-XRESUMEN
In recent years, the federal government has begun to require state agencies to allocate drug prevention resources according to the needs of local communities. The methods by which this is to be accomplished have not been described, and most published social indicator studies in the field of drug abuse research have used county-level data which are too insensitive to local needs to be of use in resource allocation decisions. The present study describes a needs assessment in drug abuse prevention in the state of New Jersey using municipal-level social indicator data. In addition, it examines the extent to which the resource allocation of one state prevention agency can be predicted by the municipal-level social indicators. Thirty-six social indicators pertaining to 508 municipalities were used in the study, and data were analyzed using principal component analysis and hierarchical regression analysis. Five factors were extracted from the principal component analysis, two of which clearly describe "high risk" municipalities and one of which clearly describes "low risk" municipalities. The regression analysis showed that these factors explained very little of the variance in the state agency's drug prevention spending. The study shows that social indicators can be used to distinguish between different levels of need for drug prevention services at a municipal level, and that these data can be used to inform decisions concerning resource allocation.
Asunto(s)
Planificación en Salud Comunitaria/métodos , Control de Medicamentos y Narcóticos , Asignación de Recursos para la Atención de Salud/métodos , Evaluación de Necesidades , Trastornos Relacionados con Sustancias/prevención & control , Alcoholismo/prevención & control , Análisis Factorial , Humanos , New Jersey , Análisis de Regresión , Factores SocioeconómicosRESUMEN
The purpose of this study was to examine the relationship among sociodemographic variables, alcohol outlet density, and rate of domestic violence in New Jersey. Data were obtained for the 223 largest municipalities in the state and were examined using factor analysis and bivariate and multivariate analyses. Three sociodemographic factors were extracted through factor analysis. These explained 58% of the variance among municipalities in rates of domestic violence. One factor--termed social disadvantage--explained the greatest amount of unique variance (42%). Alcohol outlet density added nothing to the sociodemographic model and did not interact with any of the three sociodemographic factors. The findings show that, in the state of New Jersey, higher levels of alcohol outlet density are not geographically associated with higher rates of domestic violence. These findings may be due to limitations in the data sets employed in the study, limitations of the macrolevel analysis employed, and/or the complex nature of the relationship between alcohol use and domestic violence.
Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Violencia Doméstica , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/economía , Niño , Violencia Doméstica/economía , Violencia Doméstica/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , New Jersey/epidemiología , Análisis de Regresión , Factores SocioeconómicosRESUMEN
The relationship between violent crime, neighborhood sociodemographic characteristics, and alcohol outlet densities in Newark, New Jersey is reported, thus extending previous research of municipalities at more refined levels of analysis. Alcohol outlet densities were significant predictors in regression models, but rates of violent crime were better predicted in larger units (R2 = .673 for the census tract level vs. .543 at the census block group level). Alcohol outlet densities, however, were more predictive of violent crime at smaller units of analysis (change in R2 with the addition of alcohol outlet densities was .194 at the census tract level vs. .278 at the census block group level). Findings suggest that alcohol outlets represent a form of "undesirable land use" in urban neighborhoods that are a manifestation of increasingly concentrated economic disadvantage in the United States.
Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Comercio , Crimen/estadística & datos numéricos , Femenino , Humanos , Masculino , New Jersey/epidemiología , Análisis de Regresión , Características de la Residencia , Factores Socioeconómicos , Población Urbana , Violencia/estadística & datos numéricosRESUMEN
OBJECTIVES: This study examined the relationship between rate of assaultive violence and density of alcohol outlets in New Jersey. METHODS: Data pertaining to assaultive violence, alcohol outlet density, and sociodemographic factors were obtained from municipalities in New Jersey (n = 223) and assessed through bivariate and multivariate analyses. RESULTS: Sociodemographic factors accounted for 70% (R(2)=.70) of the variance in the rate of assaultive violence. Outlet density did not add significantly to the explained variance of this model. CONCLUSIONS: In New Jersey, alcohol outlet density is not geographically associated with higher rates of violence. Alternative methodological and analytic techniques are required to better specify the relationship between alcohol availability and violence.