RESUMEN
Engaging in competitive sports as a youth can have many health benefits, but recent studies also report a high risk for injury. The long-term purpose of this Swedish research program is to develop a framework for safe track and field training for young athletes (aged 12-15 years). The aim of this study was to establish what is perceived to contribute and cause injuries in youth track and field by compiling the best available experiential knowledge about the underlying factors and use this knowledge to identify appropriate areas to handle these in practical ways. Nine focus group interviews with in total 74 participants and confirming interviews with five individuals were performed in seven Swedish regions. Qualitative research methods were used for data analysis. Injuries in youth athletes were not considered to be strictly the result of individual factors but rather the result of the interactions between factors at different levels. Three major factors emerged as follows: Insufficient knowledge for athletic development in daily practice; shortsighted communities of practice and sports policies not adjusted to youth; and societal health behaviors. The experiential knowledge in the national sporting community suggests that if effective and sustainable injury prevention processes are to be implemented for youth track and field, an ecological (holistic-developmental) approach to injury prevention is needed. Such an approach allows a longitudinal development-focused strategy for prevention that spans an athlete's entire career.
Asunto(s)
Traumatismos en Atletas/etiología , Traumatismos en Atletas/prevención & control , Atletismo/lesiones , Deportes Juveniles/lesiones , Adolescente , Adulto , Anciano , Causalidad , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Factores de Riesgo , Suecia , Adulto JovenRESUMEN
Recognized side effects on health associated with sports participation in youth include overtraining, doping, and exposure to harassment and violence. Many of these effects originate in contexts where young athletes are beginning to make decisions about their sports practices on their own. This study sets out to explore knowledge and reasoning about health among adolescent athletes and to describe how health knowledge management structures are associated with different social systems. Qualitative data were collected from focus groups involving 65 young Swedish athletes aged 16-17 years. The participants' knowledge and reasoning about health were examined using a deductive thematic analysis, categories from Bloom's taxonomy of educational objectives, and Luhmann's social systems theory. The meaning of health was found to have a dynamic character for the young athletes, associated with constantly striving to satisfy immediate needs and fulfill short-time life goals. The athletes' thinking about health was associated with a pragmatic "health-as-a-resource" perspective, characterized by group self-comparisons, rapid cognitive processing, and opportunistic substitutions. They expressed a particular interest in experiential learning and personally relevant procedural knowledge, and they perceived that their factual knowledge about health was saturated. The results of this study add emphasis to the importance of involving adolescent sportspersons in the development of health education programs and contextualizing the programs to the athletes' specific age and social environment.
Asunto(s)
Atletas/psicología , Conocimientos, Actitudes y Práctica en Salud , Aprendizaje , Adolescente , Grupos Focales , Humanos , Investigación Cualitativa , SueciaRESUMEN
BACKGROUND: Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population. METHODS AND RESULTS: Data on consecutive CRT patients was collected. 401 patients with LBBB and available ECG data were included in the study. QuAReSS software was used to perform Selvester scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The endpoint was death or heart transplant; outcome was analyzed using Cox proportional hazards models. A Selvester score >8 was significantly associated with higher risk of the combined endpoint (HR 1.59, p=.014, CI 1.09-2.3). CONCLUSION: Higher Selvester scores correlate to mortality in CRT patients with strict LBBB and might be of value in prognosticating survival.
Asunto(s)
Bloqueo de Rama/mortalidad , Bloqueo de Rama/fisiopatología , Terapia de Resincronización Cardíaca/mortalidad , Anciano , Electrocardiografía , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Suecia/epidemiologíaRESUMEN
OBJECTIVES: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology. MATERIALS AND METHODS: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age). RESULTS: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays. CONCLUSIONS: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.
Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Acueducto del Mesencéfalo/diagnóstico por imagen , Acueducto del Mesencéfalo/fisiología , Líquido Cefalorraquídeo/fisiología , Hidrocéfalo Normotenso/diagnóstico por imagen , Hidrocéfalo Normotenso/fisiopatología , Anciano , Anciano de 80 o más Años , Ventrículos Cerebrales/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Flujo Pulsátil/fisiología , Estudios Retrospectivos , Método Simple CiegoRESUMEN
The organization of sports at the national level has seldom been included in scientific discussions of sports injury prevention. The aim of this study was to develop a model for organization of sports that supports prevention of overuse injuries. The quality function deployment technique was applied in seminars over a two-season period to develop a national organizational structure for athletics in Sweden that facilitates prevention of overuse injuries. Three central features of the resulting model for organization of sports at the national level are (a) diminishment of the organizational hierarchy: participatory safety policy design is introduced through annual meetings where actors from different sectors of the sporting community discuss training, injury prevention, and sports safety policy; (b) introduction of a safety surveillance system: a ubiquitous system for routine collection of injury and illness data; and (c) an open forum for discussion of safety issues: maintenance of a safety forum for participants from different sectors of the sport. A nonhierarchical model for organization of sports at the national level - facilitated by modern information technology - adapted for the prevention of overuse injuries has been developed. Further research is warranted to evaluate the new organizational model in prospective effectiveness studies.
Asunto(s)
Trastornos de Traumas Acumulados/prevención & control , Modelos Organizacionales , Vigilancia de la Población , Deportes , Traumatismos en Atletas/prevención & control , Humanos , Cultura Organizacional , Política Organizacional , Administración de la Seguridad/métodos , SueciaRESUMEN
BACKGROUND: The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index. METHODS: In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD). RESULTS: The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012). CONCLUSIONS: This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Obesidad/genética , Polimorfismo de Nucleótido Simple , Proteínas/genética , Análisis de Secuencia de ADN/métodos , Delgadez/genética , Población Blanca/genética , Adolescente , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Composición Corporal/genética , Índice de Masa Corporal , Niño , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Obesidad/epidemiología , Delgadez/epidemiologíaRESUMEN
OBJECTIVE: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-ß-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men. DESIGN: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children. RESULTS: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038). CONCLUSION: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.
Asunto(s)
Índice de Masa Corporal , Peso Corporal , Ácidos Grasos/metabolismo , Resistencia a la Insulina , N-Acetilglucosaminiltransferasas/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Adolescente , Peso Corporal/genética , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Grecia/epidemiología , Humanos , Resistencia a la Insulina/genética , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/metabolismo , Suecia/epidemiologíaRESUMEN
OBJECTIVE: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. DESIGN: Longitudinal cohort study. SUBJECTS: Obese children (n = 231) and their parents (n = 462) from the Swedish National Childhood Obesity Centre. METHODS: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. RESULTS: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P = 0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P < 0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. CONCLUSION: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.
Asunto(s)
Índice de Masa Corporal , Obesidad/epidemiología , Padres , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Análisis Multivariante , Probabilidad , Índice de Severidad de la Enfermedad , Clase Social , Suecia/epidemiologíaRESUMEN
BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.
Asunto(s)
Glucemia/genética , Resistencia a la Insulina/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Índice de Masa Corporal , Niño , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Fenotipo , Adulto JovenRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome with familial and sporadic forms. Most ALS-associated mutations are found in the superoxide dismutase 1 (SOD1) gene. We conducted a study including 60 sporadic and 19 familial ALS patients, 206 reference patients with other neurological disorders and 40 age- and sex-matched healthy controls to test the hypothesis that cerebrospinal fluid (CSF) levels of neurofilament light (NF-L) protein, a marker of axonal degeneration, might provide diagnostic and prognostic information on the disease. All ALS patients were screened for SOD1 mutations. Ten of the familial and five of the sporadic cases carried SOD1 mutations. NF-L concentration [median (range)] was strongly elevated in ALS [2110 (255-10 800) ng/l] compared with reference patients and healthy controls [277 (<125-15 506) and 175 (<125-710) ng/l, respectively, P < 0.001] and correlated inversely with disease duration (Spearman R = -0.518, P = 0.001). NF-L levels were lower in SOD1 mutation-associated ALS compared with SOD1 wild-type (wt) ALS (P = 0.03). In conclusion, CSF NF-L levels may provide both diagnostic and prognostic information, particularly in SOD1 wt ALS.
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Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/genética , Líquido Cefalorraquídeo/metabolismo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Superóxido Dismutasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/diagnóstico , Biomarcadores/análisis , Biomarcadores/líquido cefalorraquídeo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiopatología , Líquido Cefalorraquídeo/química , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neurofilamentos/análisis , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Superóxido Dismutasa-1RESUMEN
The present study investigates the effect of the glucocorticoid corticosterone on microglial glutamate transporters in vitro. Microglial cultures obtained from rat cerebral cortex were found to express the excitatory amino acid transporter GLT-1, but not GLAST, and this expression was increased by 1 ng/ml lipopolysaccharide after 12 h of stimulation. This increase has previously been shown to be mediated by tumor necrosis factor-alpha, a cytokine released by microglia during pathological conditions. Furthermore, lipopolysaccharide increased the microglial release of tumor necrosis factor-alpha and 1 microM corticosterone inhibited this effect. Corticosterone also inhibited the lipopolysaccharide-induced increase of the GLT-1 expression as well as the expression in non-activated cells. The effect of corticosterone on the GLT-1 expression was dose dependent and accompanied by similar effects on the microglial glutamate uptake capacity. Additionally, exogenous tumor necrosis factor-alpha was found to counteract the effect of corticosterone on microglial GLT-1 expression. The effect of corticosterone appeared to be glucocorticoid receptor specific since 10 microM of the glucocorticoid receptor antagonist mifepristone inhibited the effect. Thus, corticosterone decreased the microglial uptake of glutamate by decreasing the expression of glutamate transporters, probably due to the inhibited microglial tumor necrosis factor-alpha release. These results provide insights into the mechanisms behind microglial glutamate transporter expression during pathological conditions, and contribute to the debate about the beneficial or harmful effects of glucocorticoids.
Asunto(s)
Antiinflamatorios/farmacología , Corticosterona/farmacología , Transportador 2 de Aminoácidos Excitadores/metabolismo , Expresión Génica/efectos de los fármacos , Microglía/efectos de los fármacos , Análisis de Varianza , Animales , Animales Recién Nacidos , Western Blotting/métodos , Células Cultivadas , Corteza Cerebral/citología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Ensayo de Inmunoadsorción Enzimática/métodos , Transportador 2 de Aminoácidos Excitadores/genética , Ácido Glutámico/metabolismo , Antagonistas de Hormonas/farmacología , Inmunohistoquímica/métodos , Mifepristona/farmacología , Polisacáridos/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The purpose of this study was to evaluate the value of additive components and colloid included in the University of Wisconsin (UW) solution. Therefore, this solution was compared with a solution consisting of the basic components of the UW solution (potassium lactobionate, raffinose, phosphate buffer and MgSO4). We employed a method of measuring the amount of chromium-51-labeled erythrocyte trapped in the medullary vasculature 20 min after reperfusion of kidney grafts cold-stored for 24-48 h in either the basic UW (bUW) or the original UW (oUW) solution. The amount of trapping has been shown to correlate well with the degree of cold ischemic injury. Both hemodiluted (hct 20-27%) and normal (hct 41-45%) recipients were used. Long-term viability of grafts stored in either bUW or oUW was investigated in survival experiments and the flow rates during in situ flush-out were also measured, as well as weight changes during the storage period. The results showed no significant difference between the two solutions, regardless of ischemia time or whether hemodiluted or normal recipients were used. However, the flow rate and weight measurements showed that flushing was more rapid and kidney swelling less pronounced using oUW. Survival rates in long-term transplantation experiments were similar. It was concluded that the inclusion of a colloid improves the rheological properties of the UW solution and that the additives besides the basic components did not offer any advantage.
Asunto(s)
Riñón , Preservación de Órganos/métodos , Animales , Tampones (Química) , Frío , Hematócrito , Isquemia , Riñón/irrigación sanguínea , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The role of recipient hemodilution for postischemic renal medullary red cell trapping was investigated after different periods of cold storage in a conventional cold storage solution (Sacks'). At all cold storage times investigated (4, 12, 24, and 48 hr) medullary red cell trapping was reduced by isovolemic hemodilution, with about 50% reduction of recipient hematocrit. Trapping was also reduced when a modification of a new preservation solution (University of Wisconsin solution [UW]) was used and compared with flush-out and storage in a standard preservation solution (Sacks'). The combination of hemodilution and preservation in modified UW solution had additional capacity to reduce medullary red cell trapping. Thus, even after 48 hr of cold storage, only a moderate trapping was observed. The results also indicate that measurements of medullary red cell trapping offers an accurate method of grading postischemic renal damage.
Asunto(s)
Eritrocitos/metabolismo , Hemodilución , Isquemia/complicaciones , Trasplante de Riñón , Soluciones Preservantes de Órganos , Preservación de Órganos , Adenosina , Alopurinol , Animales , Frío , Glutatión , Insulina , Riñón/irrigación sanguínea , Riñón/fisiología , Masculino , Preservación de Órganos/métodos , Rafinosa , Ratas , Ratas Endogámicas , SolucionesRESUMEN
A major cause of organ graft loss after heart transplantation is accelerated atherosclerosis. In this study we used aorta allografts and investigated the effect of estradiol-17 beta treatment on both the degree of myointimal hyperplasia and morphological changes evaluated by light and electron microscopy. Outbred New Zealand white male rabbits (2.7-3.5 kg) were fed cholesterol (0.5%) from one week prior to transplantation, and until sacrifice three weeks later. The donor abdominal aorta was transplanted end-to-end to the right carotid artery of the recipient animals. Immediately following surgery, cyclosporine (10 mg/kg/d s.c.) was administered to prevent graft rejection. The allograft recipients were randomly assigned to one of five groups and treated with cottonseed oil (placebo) or estradiol cypionate at 1, 10, 100, or 1000 micrograms/kg/d i.m. for 3 weeks. The aorta grafts were harvested and fixed for transmission electron microscopy and morphometry. The area of myointimal thickening was calculated as a percent of total vessel area (mean +/- SEM); the control group was 6.6 +/- 0.5% (n = 5). Estradiol treatment significantly inhibited (P less than 0.05) myointimal hyperplasia at all doses. The values were 3.9 +/- 0.6% (n = 6) for 1 microgram/kg/day; 4.4 +/- 0.7% (n = 5) for 10 micrograms/kg/day; 3.5 +/- 0.4% (n = 6) for 100 micrograms/kg/day; and 2.9 +/- 0.1% (n = 3) for 1000 micrograms/kg/day. Electron microscopic evaluation revealed that the four doses of estradiol protected the endothelium from the degenerative changes seen in all aorta allografts from the animals in the control group. Furthermore 10, 100, and 1000 micrograms/kg/day of estradiol prevented the appearance of vacuolized macrophages (foam cells) and also the vacuolization of smooth muscle cells that was observed in the aorta allografts from the control group and the group treated with 1 microgram/kg/day of estradiol. We conclude that the inhibitory effect of estradiol on the development of graft atherosclerosis may be due to inhibition of smooth muscle cell proliferation and preservation of ultrastructurally normal endothelial cells. The inhibitory effect on foam cell production and a concomitant vacuolization of smooth muscle cells may play a lesser role. We suggest that estrogen replacement therapy may be beneficial in postmenopausal women with organ allografts.
Asunto(s)
Aorta/trasplante , Estradiol/farmacología , Macrófagos/citología , Miocardio/patología , Animales , Aorta/ultraestructura , Aorta Abdominal , Colesterol/sangre , Hiperplasia , Masculino , Microscopía Electrónica , Músculo Liso Vascular/ultraestructura , Conejos , Trasplante Homólogo , Triglicéridos/sangreRESUMEN
Accelerated coronary atherosclerosis is the limiting factor for long-term survival of cardiac transplant recipients, but its pathogenesis is poorly understood. Morphologic and ultrastructural changes in suitable models may help explain the underlying mechanisms. In this study, early (3, 7, 14, and 21 days) and late (42 days) ultrastructural changes of the coronary artery were characterized in rabbit cardiac allografts. Thirty-four New Zealand white male rabbits (3.0-4.0 kg) served as donors and recipients. All recipients received cyclosporine (10 mg/kg/day i.m.) as immunosuppressant. In order to increase the normally very low cholesterol levels in rabbits, both the donor and recipient animals were fed a 0.5% cholesterol diet. Recipient animals were sacrificed between 3 days and 6 weeks after transplantation. The specimens from both donor and recipient were examined by transmission electron microscopy, immunohistochemistry, and morphometry. Our data indicate that intimal thickening was initiated with smooth muscle cell migration within 1 week after transplantation, and occurrence of macrophage-derived foam cells and vacuolized smooth muscle cells 3 weeks after transplantation. These changes occurred in the presence of an ultrastructurally intact endothelium. Platelets were only seldom seen adhering to the endothelium. In contrast, lymphocytes and monocytes were frequently found adhering to the endothelium at 2 and 3 weeks posttransplantation. From 3 weeks posttransplantation, lymphocytes were seen only occasionally in the intima but not in the media. This study suggests that early events elicit a change in the smooth muscle cells in the media to the secretory phenotype that migrates to the intima and proliferate. Lymphocyte and monocyte adhesion to the endothelium may enhance smooth muscle migration and proliferation. The large macrophage involvement may relate to the high serum cholesterol levels induced by the cholesterol diet. All these changes occurred in the presence of a structurally normal endothelium and without apparent platelet involvement.
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Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Trasplante de Corazón/efectos adversos , Trasplante Heterotópico , Animales , Arterias/patología , Colesterol/sangre , Colesterol en la Dieta/efectos adversos , Enfermedad de la Arteria Coronaria/etiología , Circulación Coronaria , Hiperplasia , Masculino , Microscopía Electrónica , Músculo Liso Vascular/patología , Conejos , Factores de TiempoRESUMEN
Migration and proliferation of vascular smooth muscle cells are early and major events in the formation of atherosclerotic lesions. We report on an aorta transplant model in rabbits wherein myointimal proliferation is inhibited by 17-beta-estradiol. The abdominal aortas of outbred white New Zealand rabbits were harvested and allografted to the carotid artery of the recipient. The animals, which were fed either a normal or a high-cholesterol (0.5%) diet, were killed 3 weeks later. The degree of myointimal proliferation was measured with a digitized system attached to a light microscope. The myointimal hyperplasia was expressed as the cross section area of the intima/the area of the intima + the area of the media x 100. Transmission electron micrographs were obtained for all vessels. Intimal thickening was shown mainly to consist of proliferating smooth muscle cells. The cholesterol diet resulted in significantly higher serum total cholesterol levels compared to animals on a normal diet (p < 0.0001) but did not affect serum high-density lipoprotein-cholesterol or serum triglyceride levels. The cholesterol diet was also associated with a greater but not significant amount of intimal thickening. Treatment with 17-beta-estradiol significantly decreased both serum triglyceride concentration (p < 0.05) and myointimal thickening (p < 0.01) in cholesterol-fed animals. Transmission electron microscopy showed that the endothelial cells appeared structurally normal in the estradiol-treated animals. Further, estradiol prevented the appearance of vacuolized macrophages. Thus estradiol may decrease myointimal thickening by preserving the endothelium and preventing macrophage appearance in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Aorta Abdominal/trasplante , Arteriosclerosis/prevención & control , Estradiol/farmacología , Trasplante Heterotópico/patología , Túnica Íntima/efectos de los fármacos , Animales , Aorta Abdominal/patología , Arteriosclerosis/etiología , Arteriosclerosis/patología , Arterias Carótidas , Colesterol en la Dieta/administración & dosificación , Hiperplasia/patología , Lipoproteínas/sangre , Masculino , Microscopía Electrónica , Músculo Liso Vascular/patología , Conejos , Túnica Íntima/patologíaRESUMEN
ACCESSIBLE SUMMARY: Employer/workplaces have an impact on mental health nursing staff's general attitudes towards persons with mental illness. Staff have more positive attitudes if their knowledge about mental illness is less stigmatized and currently have or have once had a close friend with mental problem. More favourable attitudes among staff towards persons with mental illness could be developed and transmitted in the subculture at work places. There is growing awareness that mental illness is surrounded by negative attitudes and stigmas. The aim of the present study was to investigate factors associated with mental health nursing staff's attitudes towards persons with mental illness. Data were collected from 256 mental health nursing staff employed by one county council and 10 municipalities. The findings show that staff have more positive attitudes towards persons with mental illness if their knowledge about mental illness is less stigmatized, their work places are in the county council, and they currently have or have once had a close friend with mental health problems. The multiple regression model explained 16% of the variance; stigma-related knowledge and employer had significant Beta-coefficients. To account for unknown correlations in data, a linear generalized estimating equation was performed. In this model, stigma-related knowledge and employer remained significant, but a new significant factor also emerged: personal contact, i.e. currently having or having once had a close friend with mental health problems. This indicates correlations at unit level in the county council and in the municipalities. The conclusion is that more favourable attitudes among staff towards persons with mental illness could be developed and transmitted in the subculture at work places.
Asunto(s)
Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Trastornos Mentales/psicología , Personal de Enfermería/normas , Enfermería Psiquiátrica/normas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In 2007, the first common genetic variants were identified, which undoubtedly affect our susceptibility to obesity. These variants are located in the fat mass and obesity-associated gene FTO. Since then, over 50 loci for common obesity have been identified. As the research on these loci is still at an early stage, there is a great need to review, for clarification purposes, the current research on FTO, as this is likely to influence future studies. Based on the current knowledge, FTO seems to be directly involved in the regulation of energy intake, but there is an urgent need for the identification of regulatory polymorphisms. Thus, herein, we discuss current knowledge and highlight putative functional regions in FTO based on published data and computer-based analysis.