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BACKGROUND: Presence of comorbid diseases at time of cancer diagnosis may affect prognosis. We evaluated the impact of comorbidity on survival of patients diagnosed with renal cell carcinoma (RCC), overall and among younger (<70 years) and older (≥70 years) patients. METHODS: We established a nationwide register-based cohort of 7894 patients aged ≥18 years diagnosed with RCC in Denmark between 2006 and 2017. We computed 1- and 5-year overall survival and hazard ratios (HRs) for death according to the Charlson Comorbidity Index (CCI) score. RESULTS: Survival decreased with increasing CCI score despite an overall increase in survival over time. The 5-year survival rate of patients with no comorbidity increased from 57% among those diagnosed in 2006-2008 to 69% among those diagnosed in 2012-2014. During the same periods, the survival rate increased from 46% to 62% among patients with a CCI score of 1-2 and from 39% to 44% for those with a CCI score of ≥3. Patients with CCI scores of 1-2 and ≥3 had higher mortality rates than patients with no registered comorbidity (HR 1.15, 95% CI 1.06-1.24 and HR 1.56, 95% CI 1.40-1.73). Patterns were similar for older and younger patients. Particularly, diagnoses of liver disease (HR 2.09, 95% CI 1.53-2.84 and HR 4.01, 95% CI 2.44-6.56) and dementia (HR 2.16, 95% CI 1.34-3.48) increased mortality. CONCLUSION: Comorbidity decreased the survival of patients with RCC, irrespective of age, despite an overall increasing survival over time. These results highlight the importance of focusing on comorbidity in this group of patients.
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Carcinoma de Células Renais , Neoplasias Renais , Adolescente , Adulto , Carcinoma de Células Renais/epidemiologia , Estudos de Coortes , Comorbidade , Humanos , Neoplasias Renais/epidemiologia , PrognósticoRESUMO
BACKGROUND: The head and neck are exposed to the highest solar ultraviolet radiation levels and experience a disproportionate skin cancer burden. Sun protective hats can provide an effective barrier. Since early life exposure contributes to skin cancer risk, the World Health Organisation recommends prevention programmes in schools. The New Zealand SunSmart Schools programme is one example. Two criteria concern wearing hat outdoors: students are required to wear a hat providing protection for the face, neck, and ears; if a suitable hat is not worn, students must play in shaded areas. OBJECTIVES: To investigate two internationally relevant interventions as plausible statistical predictors of hat policy strength: (1) skin cancer primary prevention programme membership, (2) use of a professional policy drafting service. METHODS: Of 1,242 (62%) eligible schools participating in a 2017 national survey, 1,137 reported a sun protection policy and 842 were available for categorising and allocating protective scores (0-3). RESULTS: In multinomial (polytomous) logistic regression models of cross-sectional association, adjusted for school characteristics, SunSmart accredited schools and those utilising a policy drafting service were independently significantly more likely than their counterparts to obtain the most protective compared to the least protective hat score (respectively, RRR 6.48: 95% CI 3.66, 11.47; 7.47: 3.67, and 15.20). For the dichotomous shade measure, similar associations were found using adjusted logistic regression (OR 3.28: 95% CI 2.11, 5.09; 2.70: 1.54, 4.74). CONCLUSIONS: Our findings provide support for two plausible interventions that could potentially be implemented beneficially in primary schools via established infrastructure in any jurisdiction, internationally.
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Behaviour change, specifically that which decreases cancer risk, is an essential element of cancer control. Little information is available about how awareness of risk factors may be changing over time. This study describes the awareness of cancer risk behaviours among adult New Zealanders in two cross-sectional studies conducted in 2001 and 2014/5.Telephone interviews were conducted in 2001 (n = 436) and 2014/5 (n = 1064). Participants were asked to recall things they can do to reduce their risk of cancer. They were then presented with a list of potential risk behaviours and asked if these could increase or decrease cancer risk.Most New Zealand adults could identify at least one action they could take to reduce their risk of cancer. However, when asked to provide specific examples, less than a third (in the 2014/5 sample) recalled key cancer risk reduction behaviours such as adequate sun protection, physical activity, healthy weight, limiting alcohol and a diet high in fruit. There had been some promising changes since the 2001 survey, however, with significant increases in awareness that adequate sun protection, avoiding sunbeds/solaria, healthy weight, limiting red meat and alcohol, and diets high in fruit and vegetables decrease the risk of developing cancer.
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Conscientização , Comportamentos Relacionados com a Saúde , Neoplasias/prevenção & controle , Comportamento de Redução do Risco , Adulto , Idoso , Estudos Transversais , Dieta/estatística & dados numéricos , Exercício Físico , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Inquéritos e Questionários , VerdurasRESUMO
OBJECTIVE: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to determine the concentrations of these constituents in fetal membranes in relation to gestational age, preterm labour, PPROM and chorioamnionitis. STUDY DESIGN: Preterm fetal membranes (24-34 weeks gestation) were obtained from elective caesarean deliveries (N = 4), from PPROM (N = 14), and from preterm labour (N = 14). Term fetal membranes from elective caesarean deliveries (N = 9) and spontaneous vaginal deliveries (N = 11) were used for comparison. Chorioamnionitis was assessed histologically. The proteoglycans were analysed using alcian blue precipitation, SDS-PAGE and immunostaining. Hyaluronan was estimated by a radioimmunoassay. RESULTS: Preterm amniotic membranes with chorioamnionitis displayed a 8-fold decrease in hyaluronan concentration as well as a pronounced (88%) degradation of decorin and biglycan (p < 0.05). The amnion from preterm elective caesarean sections had higher decorin (3.2 vs. 1.7 µg/mg, p < 0.05) and lower biglycan (0.4 vs. 1.0 µg/mg, p < 0.05) concentrations as compared to similar term amnion (p < 0.05), whereas the hyaluronan concentrations were not associated with gestational age. Also the chorio-decidua from preterm caesarean sections had higher decorin concentrations (1.8 vs. 1.0 µg/mg, p < 0.05) whereas the biglycan concentration was unchanged. Labour (term as well as preterm) was characterized by increased hyaluronan and biglycan concentrations in the amnion (not statistically significant). CONCLUSION: The biglycan/decorin balance increases during third trimester of pregnancy and during active labour. This relation might contribute to mechanical weakening of the membranes. Chorioamnionitis induces dramatic degradation of both proteoglycans and hyaluronan, which can explain the decreased biomechanical strength.
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Biglicano/metabolismo , Corioamnionite/metabolismo , Decorina/metabolismo , Membranas Extraembrionárias/metabolismo , Ácido Hialurônico/metabolismo , Nascimento Prematuro/metabolismo , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Hidroxiprolina/metabolismo , GravidezRESUMO
AIM: Production of reactive oxygen species (ROS) in skeletal muscle is markedly increased during exercise and may be essential for exercise adaptation. We, therefore, investigated the effects of infusion with the antioxidant N-acetylcysteine (NAC) on exercise-induced activation of signalling pathways and genes involved in exercise adaptation in human skeletal muscle. METHODS: Subjects completed two exercise tests, 7 days apart, with saline (control, CON) or NAC infusion before and during exercise. Exercise tests comprised of cycling at 71% VO(2peak) for 45 min, and then 92% VO(2peak) to fatigue, with vastus lateralis biopsies at pre-infusion, after 45-min cycling and at fatigue. RESULTS: Analysis was conducted on the mitogen-activated protein kinase signalling pathways, demonstrating that NAC infusion blocked the exercise-induced increase in JNK phosphorylation, but not ERK1/2, or p38 MAPK. Nuclear factor-κB p65 phosphorylation was unaffected by exercise; however, it was reduced in NAC at fatigue by 14% (P < 0.05) compared with pre-infusion. Analysis of exercise and/or ROS-sensitive genes demonstrated that exercise-induced mRNA expression is ROS dependent of MnSOD, but not PGC-1α, interleukin-6, monocyte chemotactic protein-1, or heat-shock protein 70. CONCLUSION: These results suggest that inhibition of ROS attenuates some skeletal muscle cell signalling pathways and gene expression involved in adaptations to exercise.
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Acetilcisteína/administração & dosagem , Antioxidantes/administração & dosagem , Exercício Físico , Contração Muscular , Estresse Oxidativo/efeitos dos fármacos , Músculo Quadríceps/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Adaptação Fisiológica , Adulto , Análise de Variância , Ciclismo , Biópsia , Quimiocina CCL2/genética , Estudos Cross-Over , Método Duplo-Cego , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Humanos , Proteínas I-kappa B/metabolismo , Infusões Intravenosas , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Fadiga Muscular , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Consumo de Oxigênio , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosforilação , Músculo Quadríceps/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/genética , Fatores de Tempo , Fatores de Transcrição/genética , Vitória , Adulto JovemRESUMO
AIM: This study investigated the effects of endurance training status and sex differences on skeletal muscle Na+,K+-pump mRNA expression, content and activity. METHODS: Forty-five endurance-trained males (ETM), 11 recreationally active males (RAM), and nine recreationally active females (RAF) underwent a vastus lateralis muscle biopsy. Muscle was analysed for Na+,K+-pump alpha1, alpha2, alpha3, beta1, beta2 and beta3 isoform mRNA expression (real-time reverse transcription-polymerase chain reaction), content ([3H]-ouabain-binding site) and maximal activity (3-O-methylfluorescein phosphatase, 3-O-MFPase). RESULTS: ETM demonstrated lower alpha1, alpha3, beta2 and beta3 mRNA expression by 74%, 62%, 70% and 82%, respectively, than RAM (P<0.04). In contrast, [3H]-ouabain binding and 3-O-MFPase activity were each higher in ETM than in RAM, by 16% (P<0.03). RAM demonstrated a 230% and 364% higher alpha3 and beta3 mRNA expression than RAF, respectively (P<0.05), but no significant sex differences were found for alpha1, alpha2, beta1 or beta2 mRNA, [3H]-ouabain binding or 3-O-MFPase activity. No significant correlation was found between years of endurance training and either [3H]-ouabain binding or 3-O-MFPase activity. Significant but weak correlations were found between the number of training hours per week and 3-O-MFPase activity (r=0.31, P<0.02) and between incremental exercise VO2(peak)) and both [3H]-ouabain binding (r=0.33, P<0.01) and 3-O-MFPase activity (r=0.28, P<0.03). CONCLUSIONS: Isoform-specific differences in Na+,K+-pump mRNA expression were found with both training status and sex differences, but only training status influenced Na+,K+-pump content and maximal activity in human skeletal muscle.
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Regulação da Expressão Gênica , Músculo Esquelético/enzimologia , Resistência Física , Isoformas de Proteínas/genética , RNA Mensageiro/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Análise de Variância , Sítios de Ligação , Biópsia , Estudos Transversais , Ciclofilinas/genética , Ativação Enzimática , Feminino , Humanos , Masculino , Ouabaína/metabolismo , Educação Física e Treinamento , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , ATPase Trocadora de Sódio-Potássio/análise , Fatores de TempoRESUMO
OBJECTIVE: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to compare hyaluronan and proteoglycans in human fetal membranes obtained before and after spontaneous labour at term. STUDY DESIGN: Prelabour samples of fetal membranes (N=9) were obtained from elective caesarean sections and regionally sampled from over the cervix (cervical membranes) and mid-zone samples between this area and the placental edge. Postlabour samples (N=11) were obtained from spontaneous vaginal delivery and also regionally sampled. Amnion and chorio-decidua were analysed separately. The proteoglycans decorin and biglycan were analysed using alcian blue precipitation, SDS polyacrylamide gel electrophoresis and immunostaining. Hyaluronan was analysed using a radioimmunoassay and by histochemistry. Collagen was measured by estimating hydroxyproline content. RESULTS: In prelabour membranes the biglycan concentration (microg/mg wtw) in the cervical amnion was 40% lower than in the mid-zone amnion (P<0.05). After delivery the cervical amnion showed a twofold increase in biglycan (P<0.05), a 30% decrease in collagen (P<0.05), and a 50% decrease in decorin concentration (P<0.05). In mid-zone samples after delivery the concentrations of hyaluronan showed an increase form 1.0 to 4.9 microg/mg wtw (P<0.05). Histology demonstrated a gelatinous substance, which separated amnion and chorio-decidua, in particular at the cervical site. This gelatinous substance contained hyaluronan at a concentration of 3.0 microg/mg wtw. CONCLUSION: It is well established that prelabour fetal membranes are considerably stronger than postlabour fetal membranes. Two features may explain this; a weakening of the amnion combined with a separation of amnion and chorio-decidua. The biomechanical changes are consistent with the decrease in collagen and decorin, and the increase in hyaluronan and biglycan demonstrated in this study. The separation of the membranes is caused by the formation of a gelatinous substance, rich in hyaluronan. The results indicate that the biomechanical changes are not merely secondary to the stress of labour but that an active maturation process is involved.
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Proteínas da Matriz Extracelular/metabolismo , Membranas Extraembrionárias/metabolismo , Ácido Hialurônico/metabolismo , Trabalho de Parto/fisiologia , Proteoglicanas/metabolismo , Biglicano , Colo do Útero/citologia , Colo do Útero/metabolismo , Cesárea , Colágeno/metabolismo , Feminino , Humanos , GravidezRESUMO
This study investigated effects of prolonged submaximal exercise on Na+-K+-ATPase mRNA and protein expression, maximal activity, and content in human skeletal muscle. We also investigated the effects on mRNA expression of the transcription initiator gene, RNA polymerase II (RNAP II), and key genes involved in protein translation, eukaryotic initiation factor-4E (eIF-4E) and 4E-binding protein 1 (4E-BP1). Eleven subjects (6 men, 5 women) cycled at 75.5% (SD 4.8%) peak O2 uptake and continued until fatigue. A vastus lateralis muscle biopsy was taken at rest, fatigue, and 3 and 24 h postexercise. We analyzed muscle for Na+-K+-ATPase alpha1, alpha2, alpha3, beta1, beta2, and beta3, as well for RNAP II, eIF-4E, and 4E-BP1 mRNA expression by real-time RT-PCR and Na+-K+-ATPase isoform protein abundance using immunoblotting. Muscle homogenate maximal Na+-K+-ATPase activity was determined by 3-O-methylfluorescein phosphatase activity and Na+-K+-ATPase content by [3H]ouabain binding. Cycling to fatigue [54.5 (SD 20.6) min] immediately increased alpha3 (P = 0.044) and beta2 mRNA (P = 0.042) by 2.2- and 1.9-fold, respectively, whereas alpha1 mRNA was elevated by 2.0-fold at 24 h postexercise (P = 0.036). A significant time main effect was found for alpha3 protein abundance (P = 0.046). Exercise transiently depressed maximal Na+-K+-ATPase activity (P = 0.004), but Na+-K+-ATPase content was unaltered throughout recovery. Exercise immediately increased RNAP II mRNA by 2.6-fold (P = 0.011) but had no effect on eIF-4E and 4E-BP1 mRNA. Thus a single bout of prolonged submaximal exercise induced isoform-specific Na+-K+-ATPase responses, increasing alpha1, alpha3, and beta2 mRNA but only alpha3 protein expression. Exercise also increased mRNA expression of RNAP II, a gene initiating transcription, but not of eIF-4E and 4E-BP1, key genes initiating protein translation.
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Exercício Físico/fisiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Masculino , Músculo Esquelético/enzimologia , Ouabaína/metabolismo , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
In the daily practice of science for policy, as experienced by governmental agencies which inform the policy and the public on the state and outlook of the environment, there is a pressing need for guidance in assessing and communicating uncertainties. This need extends beyond the quantitative assessment of uncertainties in model results, and focuses on the entire process of environmental assessment, running from problem framing towards reporting the results of the study. Using the Netherlands Environmental Assessment Agency (RIVM/MNP) as a case, the development, structure and content of such a guidance system is highlighted. Conditions for a successful implementation of the guidance system are discussed, and some prospects for future work are outlined.
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Comunicação , Meio Ambiente , Incerteza , Órgãos Governamentais , Países Baixos , Formulação de Políticas , Política Pública , Medição de RiscoRESUMO
We investigated whether depressed muscle Na(+)-K(+)-ATPase activity with exercise reflected a loss of Na(+)-K(+)-ATPase units, the time course of its recovery postexercise, and whether this depressed activity was related to increased Na(+)-K(+)-ATPase isoform gene expression. Fifteen subjects performed fatiguing, knee extensor exercise at approximately 40% maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue, 3 h, and 24 h postexercise and analyzed for maximal Na(+)-K(+)-ATPase activity via 3-O-methylfluorescein phosphatase (3-O-MFPase) activity, Na(+)-K(+)-ATPase content via [(3)H]ouabain binding sites, and Na(+)-K(+)-ATPase alpha(1)-, alpha(2)-, alpha(3)-, beta(1)-, beta(2)- and beta(3)-isoform mRNA expression by real-time RT-PCR. Exercise [352 (SD 267) s] did not affect [(3)H]ouabain binding sites but decreased 3-O-MFPase activity by 10.7 (SD 8)% (P < 0.05), which had recovered by 3 h postexercise, without further change at 24 h. Exercise elevated alpha(1)-isoform mRNA by 1.5-fold at fatigue (P < 0.05). This increase was inversely correlated with the percent change in 3-O-MFPase activity from rest to fatigue (%Delta3-O-MFPase(rest-fatigue)) (r = -0.60, P < 0.05). The average postexercise (fatigue, 3 h, 24 h) alpha(1)-isoform mRNA was increased 1.4-fold (P < 0.05) and approached a significant inverse correlation with %Delta3-O-MFPase(rest-fatigue) (r = -0.56, P = 0.08). Exercise elevated alpha(2)-isoform mRNA at fatigue 2.5-fold (P < 0.05), which was inversely correlated with %Delta3-O-MFPase(rest-fatigue) (r = -0.60, P = 0.05). The average postexercise alpha(2)-isoform mRNA was increased 2.2-fold (P < 0.05) and was inversely correlated with the %Delta3-O-MFPase(rest-fatigue) (r = -0.68, P < 0.05). Nonsignificant correlations were found between %Delta3-O-MFPase(rest-fatigue) and other isoforms. Thus acute exercise transiently decreased Na(+)-K(+)-ATPase activity, which was correlated with increased Na(+)-K(+)-ATPase gene expression. This suggests a possible signal-transduction role for depressed muscle Na(+)-K(+)-ATPase activity with exercise.
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Exercício Físico , Fadiga/enzimologia , Músculo Esquelético/enzimologia , RNA Mensageiro/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Volume Sanguíneo , Feminino , Humanos , Masculino , Concentração Osmolar , Potássio/sangue , Fatores de TempoRESUMO
Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na(+)-K(+)-ATPase content, whereas fatiguing contractions reduce Na(+)-K(+)-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na(+)-K(+)-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K(+) regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O(2) fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude approximately 600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na(+)-K(+)-ATPase activity [K(+)-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na(+)-K(+)-ATPase content ([(3)H]ouabain binding sites). 3-O-MFPase activity was decreased by -2.9 +/- 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (-13.0 +/- 3.2 and -11.8 +/- 1.5%, respectively). Plasma K(+) concentration during exercise was unchanged by LHTL; [(3)H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na(+)-K(+)-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K(+) regulation or total work performed.
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Altitude , Ciclismo , Exercício Físico , Hipóxia/fisiopatologia , Músculo Esquelético/fisiopatologia , Resistência Física , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Doença Crônica , Ativação Enzimática , Regulação da Expressão Gênica , Humanos , Masculino , Esportes , Fatores de TempoRESUMO
The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.
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Acetilcisteína/administração & dosagem , Cisteína/farmacocinética , Glutationa/farmacocinética , Fadiga Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Resistência Física/fisiologia , Esforço Físico/fisiologia , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço , Humanos , Infusões Intravenosas , Masculino , Fadiga Muscular/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Aptidão Física/fisiologiaRESUMO
Characterization of expression of, and consequently also the acute exercise effects on, Na(+),K(+)-ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at approximately 40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na(+),K(+)-ATPase alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) mRNA and crude homogenate protein expression, using Real-Time RT-PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na(+),K(+)-ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 +/- 69 s; mean +/-s.e.m.) immediately increased alpha(3) and beta(2) mRNA by 2.4- and 1.7-fold, respectively (P < 0.05), whilst alpha(1) and alpha(2) mRNA were increased by 2.5- and 3.5-fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for beta(1) and beta(3) mRNA, reflecting variable time-dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) isoforms, by 1.4-, 2.2-, 1.4-, 1.1-, 1.0- and 1.0-fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the alpha(1)-alpha(3) and beta(1)-beta(3) isoforms. Thus, human skeletal muscle expresses each of the Na(+),K(+)-ATPase alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na(+),K(+)-ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na(+),K(+)-ATPase up-regulation.
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Exercício Físico/fisiologia , Isoenzimas/genética , Músculo Esquelético/fisiologia , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Células Cultivadas , Feminino , Humanos , Masculino , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/enzimologia , Músculo Esquelético/citologia , RNA Mensageiro/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Regulação para Cima/fisiologiaRESUMO
OBJECTIVES: The goal of this work was to evaluate clinical and pathological findings, surgical procedures, and postoperative treatment in women with stage I granulosa cell tumor. METHODS: Data for 49 women with granulosa cell tumor were collected retrospectively. All pathological sections and findings were reviewed from diagnosis until recently. Follow-up data were collected from the general practitioner, hospital records, or death certificate. Fisher's exact test, Student's t test, Mann-Whitney test, and Kaplan-Meier survival analysis were applied, as appropriate. RESULTS: Thirty-seven women of median age 58 years (range, 33-82) were diagnosed in stage I. Follow-up time was 8 years (range, 8 months to 26 years). The estimated survival for stage I was 93% at 5 years, 84% at 10 years, and 62% at 20 years; the actual survival rates were 94, 82, and 62% after 5, 10, and 20 years, respectively. Primary treatment consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy was associated with improved survival (P < 0.05) and tended to be associated with longer relapse-free interval (P < 0.06). The 10-year survival rate was 40% in postmenopausal women operated conservatively and more than 90% for the extensively treated women (P < 0.05). Evidence of increased estrogen secretion was found more often in postmenopausal woman as compared with premenopausal women (P < 0.01) but did not affect survival. No pathological parameter correlated with prognosis. CONCLUSION: Granulosa cell tumor is a tumor of unquestionable malignant potential and has a tendency for late relapses. Long-time follow-up is recommended.
Assuntos
Tumor de Células da Granulosa/patologia , Tumor de Células da Granulosa/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Tumor de Células da Granulosa/cirurgia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/cirurgia , Radioterapia Adjuvante , Taxa de SobrevidaRESUMO
OBJECTIVE: The aim of this study was to describe the distributions of major extracellular matrix components, such as proteoglycans, collagen and hyaluronan, in the fetal membranes at term. STUDY DESIGN: Fetal membranes were obtained from elective cesarean deliveries at term. Guanidinium extracts were analyzed for proteoglycans with alcian blue precipitation, sodium dodecyl sulfate- polyacrylamide gel electrophoresis, and Western blotting and for hyaluronan with a radioimmunoassay. Collagen was measured by estimating hydroxyproline content. Tissue sections were immunostained for decorin and biglycan and stained for hyaluronan with a biotin-labeled hyaluronan-binding protein. RESULTS: The fetal membranes contained predominantly smaller proteoglycans, such as biglycan and decorin. The amnion consisted of typical fibrous connective tissue with a high concentration of collagen. The amnion was dominated by decorin located in close connection with the collagen fibrils. The chorion was composed of a fibroblastic part containing collagen and decorin and a trophoblastic part mainly containing biglycan. In addition, large amounts of hyaluronan were found, especially in the amnion and in the decidual cell layers. CONCLUSION: The distributions of proteoglycans, collagen, and hyaluronan in human fetal membranes may explain the biomechanical properties of this tissue. We suggest that changes in the relative proportions of these extracellular molecules are crucial for the proposed maturation process in the fetal membranes during the last weeks of pregnancy.
Assuntos
Membranas Extraembrionárias/química , Ácido Hialurônico/análise , Proteoglicanas/análise , Azul Alciano , Âmnio/química , Biglicano , Western Blotting , Precipitação Química , Córion/química , Colágeno/análise , Decídua/química , Decorina , Eletroforese em Gel de Poliacrilamida , Proteínas da Matriz Extracelular , Feminino , Humanos , Hidroxiprolina/análise , Gravidez , Trofoblastos/químicaRESUMO
PURPOSE: To better delineate the impact of health risk behaviors on adolescent women's current and future health and development. METHOD: The Commonwealth Fund Survey of Adolescent Health, a national survey of adolescents in Grades 5-12 designed to better understand their health and health care needs, was used as the basis for this study. Survey data were collected in 1997 from a total of 6730 adolescents (3568 females, 3162 males). Areas examined include smoking, drinking, use of other drugs, violence, safety, reproductive risks, and the prevention of risk behaviors in adolescent women. RESULTS: Adolescent women are almost equally likely to smoke, drink, and engage in other substance use as their male counterparts, but with increased health risks. Different motivations for engaging in risk behavior also are evident. Adolescent women are also more likely than adolescent men to experience physical abuse, and they are twice as likely to be sexually abused. CONCLUSIONS: Effective prevention programs need to recognize that the motivations for engaging in risk behaviors may differ by gender. Developmental awareness, proper assessment, and pivotal institutions can provide and shape what is needed for healthy development.
Assuntos
Comportamento do Adolescente , Medicina Preventiva , Assunção de Riscos , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Criança , Feminino , Comportamentos Relacionados com a Saúde , Acessibilidade aos Serviços de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Serviços Preventivos de Saúde , Fatores de Risco , Comportamento Sexual/estatística & dados numéricos , Fumar/epidemiologia , Inquéritos e Questionários , Estados Unidos/epidemiologia , Violência/estatística & dados numéricos , Saúde da MulherRESUMO
Nine laboratories in eight countries tested 16 batches of common mussels (Mytilus edulis) over a 32 week period in order to find an alternative to the Most Probable Number (MPN) technique to enumerate E. coli. The alternatives investigated included the 3M Petrifilm system, the Merck Chromocult agar method and a Malthus conductance technique. The Petrifilm was found to be unsuitable and was subsequently dropped from the trial. After 669 analyses, a correlation of 0.83 was observed for log E. coli counts between the MPN and Chromocult methods and there was no significant evidence that either method tended to give higher readings than the other. The MPN was slightly better than the Chromocult method for repeatability but the Chromocult was slightly better for reproducibility. However, the observed differences are probably too small to be of practical importance. On the basis of these data therefore, the two methods appear equally suitable for E. coli enumeration in shellfish. There were poor correlations between these methods and the Malthus technique. A small but significant number of samples tested positive on the Malthus instrument but were recorded negative on the MPN and Chromocult tests. Subsequent analysis positively identified E. coli from these Malthus assays. After statistical analysis, errors were noted in both the MPN and Chromocult methods but it was found that there would be no statistical differences if the Chromocult agar were used as an alternative to the MPN technique.