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1.
Science ; 384(6692): 214-217, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38603482

RESUMO

Massive stars (those ≥8 solar masses at formation) have radiative envelopes that cannot sustain a dynamo, the mechanism that produces magnetic fields in lower-mass stars. Despite this, approximately 7% of massive stars have observed magnetic fields, the origin of which is debated. We used multi-epoch interferometric and spectroscopic observations to characterize HD 148937, a binary system of two massive stars. We found that only one star is magnetic and that it appears younger than its companion. The system properties and a surrounding bipolar nebula can be reproduced with a model in which two stars merged (in a previous triple system) to produce the magnetic massive star. Our results provide observational evidence that magnetic fields form in at least some massive stars through stellar mergers.

3.
Public Health ; 127(12): 1090-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24267904

RESUMO

OBJECTIVE: The purpose of this study was to examine the prevalence of obesity over time in the same individuals comparing body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR). STUDY DESIGN: Five year longitudinal repeated measures study (2005-2010). Children were aged 11-12 (Y7) years at baseline and measurements were repeated at age 13-14 (Y9) years and 15-16 (Y11) years. METHODS: WC and BMI measurements were carried out by the same person over the five years and raw values were expressed as standard deviation scores (sBMI and sWC) against the growth reference used for British children. RESULTS: Mean sWC measurements were higher than mean sBMI measurements for both sexes and at all assessment occasions and sWC measurements were consistently high in girls compared to boys. Y7 sWC = 0.792 [95% confidence interval (CI) 0.675-0.908], Y9 sWC = 0.818 (95%CI 0.709-0.928), Y11 sWC = 0.943 (95%CI 0.827-1.06) for boys; Y7 sWC = 0.843 (0.697-0.989), Y9 sWC = 1.52 (95%CI 1.38-0.67), Y11 sWC = 1.89 (95%CI 1.79-2.04) for girls. Y7 sBMI = 0.445 (95%CI 0.315-0.575), Y9 sBMI = 0.314 (95%CI 0.189-0.438), Y11 sBMI = 0.196 (95%CI 0.054-0.337) for boys; Y7 sBMI = 0.353 (0.227-0.479), Y9 sBMI = 0.343 (95%CI 0.208-0.478), Y11 sBMI = 0.256 (95%CI 0.102-0.409) for girls. The estimated prevalence of obesity defined by BMI decreased in boys (18%, 12% and 10% in Y 7, 9 and 11 respectively) and girls (14%, 15% and 11% in Y 7, 9 and 11). In contrast, the prevalence estimated by WC increased sharply (boys; 13%, 19% and 23%; girls, 20%, 46% and 60%). CONCLUSION: Central adiposity, measured by WC is increasing alongside a stabilization in BMI. Children appear to be getting fatter and the additional adiposity is being stored centrally which is not detected by BMI. These substantial increases in WC are a serious concern, especially in girls.


Assuntos
Índice de Massa Corporal , Obesidade Infantil/epidemiologia , Circunferência da Cintura , Adolescente , Estatura , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência
4.
Glob Chang Biol ; 19(5): 1620-31, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23505160

RESUMO

The impact of climate change and of other anthropogenic pressures on the structure and composition of phytoplankton communities of large European rivers remains poorly documented. Here we report the findings of a study of the changes in the phytoplankton community of the middle segment of the river Loire over the past 24 years. An attempt is made to distinguish between the impact of changes acting at the local scale and that of those acting more globally. A dramatic reduction in phytoplankton abundance was observed, particularly in the mid -1990s; this was concomitant with an increase in the relative proportion of cyanobacteria. At the same time, the phytoplankton community displayed increasing richness and diversity, and little change in its size structure. All these changes seem to be related to local changes, in particular to the reduction in phosphorus concentrations, as well as to changes in climate, throughout modifications in the river discharge and water temperature. Interestingly, herbicide contamination also appeared to be of particular importance in explaining the unexpected increase in the proportion of cyanobacteria in the phytoplankton community after the 1990s. These findings suggest that combinations of numerous anthropogenic pressures acting at different spatial and temporal scales have led to a mix of predictable and unpredictable changes occurring in the phytoplankton community of the river Loire, with probable consequences for the trophic networks in this river.


Assuntos
Biota , Mudança Climática , Fitoplâncton/fisiologia , Rios/química , Biomassa , Cianobactérias/fisiologia , França , Fósforo/análise , Estações do Ano
5.
Int J Obes (Lond) ; 37(4): 486-92, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23399775

RESUMO

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level.


Assuntos
Adiposidade , Obesidade/epidemiologia , Pobreza/estatística & dados numéricos , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Cadeias de Markov , Obesidade/etiologia , Obesidade/prevenção & controle , Prevalência , Distribuição por Sexo , Reino Unido/epidemiologia
6.
Neurotox Res ; 22(1): 79-90, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22311271

RESUMO

Oxygen interruption leads to death when re-oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of biochemical events for restoring function at the cost of improper homeostasis. The effects observed long after perinatal asphyxia (PA) have been explained by over-expression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a therapeutic strategy. We studied the effects of nicotinamide and theophylline on PARP-1 activity assayed in brain and peripheral (heart) rat tissue 1-24 h after birth, as well as on changes in behaviour and monoamine neurotransmission in adult rats. PA was induced by immersing rat foetuses into a water bath for 0 or 21 min. After resuscitation, the pups were treated with nicotinamide (0.8 mmol/kg, i.p.), theophylline (0.14 mmol/kg, i.p.) or saline (0.9% NaCl) and nurtured by surrogate dams, pending behavioural and microdialysis experiments, or euthanised after birth for assaying PARP-1 activity. To estimate the in vivo distribution of a single dose of nicotinamide or theophylline into brain and peripheral compartment, a series of animals were implanted with microdialysis probes, one into the brain and other subcutaneously, 1 h after birth, assaying the drugs with a HPLC-UV system. Nicotinamide, but not theophylline prevented the long-term effects induced by PA. Only nicotinamide produced a consistent decrease in PARP-1 activity in brain and heart, whether assayed in control or asphyxia-exposed pups. The present results support the idea that the long-term effects induced by PA imply PARP-1 over-activation.


Assuntos
Asfixia/metabolismo , Comportamento Animal/efeitos dos fármacos , Niacinamida/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Teofilina/farmacologia , Complexo Vitamínico B/farmacologia , Animais , Animais Recém-Nascidos/metabolismo , Asfixia Neonatal/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Coração/efeitos dos fármacos , Humanos , Recém-Nascido , Microdiálise , Modelos Animais , Miocárdio/metabolismo , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Ratos , Ratos Wistar
7.
J Bone Joint Surg Br ; 93(8): 1027-32, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21768624

RESUMO

Labral tears are commonly associated with femoroacetabular impingement. We reviewed 151 patients (156 hips) with femoroacetabular impingement and labral tears who had been treated arthroscopically. These were subdivided into those who had undergone a labral repair (group 1) and those who had undergone resection of the labrum (group 2). In order to ensure the groups were suitably matched for comparison of treatment effects, patients with advanced degenerative changes (Tönnis grade > 2, lateral sourcil height < 2 mm and Outerbridge grade 4 changes in the weight-bearing area of the femoral head) were excluded, leaving 96 patients (101 hips) in the study. At a mean follow-up of 2.44 years (2 to 4), the mean modified Harris hip score in the labral repair group (group 1, 69 hips) improved from 60.2 (24 to 85) pre-operatively to 93.6 (55 to 100), and in the labral resection group (group 2, 32 hips) from 62.8 (29 to 96) pre-operatively to 88.8 (35 to 100). The mean modified Harris hip score in the labral repair group was 7.3 points greater than in the resection group (p = 0.036, 95% confidence interval 0.51 to 14.09). Labral detachments were found more frequently in the labral repair group and labral flap tears in the resection group. No patient in our study group required a subsequent hip replacement during the period of follow-up. This study shows that patients without advanced degenerative changes in the hip can achieve significant improvement in their symptoms after arthroscopic treatment of femoroacetabular impingement. Where appropriate, labral repair provides a superior result to labral resection.


Assuntos
Artroscopia/métodos , Cartilagem Articular/cirurgia , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Adolescente , Adulto , Idoso , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Feminino , Impacto Femoroacetabular/diagnóstico por imagem , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
8.
Cochrane Database Syst Rev ; (4): CD006304, 2007 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-17943903

RESUMO

BACKGROUND: Perineal trauma is common during childbirth and may be painful. Contemporary maternity practice includes offering women numerous forms of pain relief, including the local application of cooling treatments. OBJECTIVES: To evaluate the effectiveness and side effects of localised cooling treatments compared with no treatment, other forms of cooling treatments and non-cooling treatments. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), CINAHL (1982 to January 2007) and contacted experts in the field. SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials (RCTs) that compared localised cooling treatment applied to the perineum with no treatment or other treatments applied to relieve pain related to perineal trauma sustained during childbirth. DATA COLLECTION AND ANALYSIS: At least two independent authors performed data extraction for each study. Analyses were performed on an intention-to-treat basis where data allowed. We sought additional information from the authors of three trials. MAIN RESULTS: Seven published RCTs were included, comparing local cooling treatments (ice packs, cold gel pads or cold/iced baths) with no treatment, hamamelis water (witch hazel), pulsed electromagnetic energy (PET), hydrocortisone/pramoxine foam [Epifoam] or warm baths. The RCTs reported on a total of 859 women. Ice packs provided improved pain relief 24 to 72 hours after birth compared with no treatment (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.41 to 0.91). Women preferred the utility of the gel pads compared with ice packs or no treatment, although no differences in pain relief were detected between the treatments. None of our comparisons of treatments resulted in differences detected in perineal oedema or bruising. Women reported more pain (RR 5.60, 95% CI 2.35 to 13.33) and used more additional analgesia (RR 4.00, 95% CI 1.44 to 11.13) following the application of ice packs compared with PET. AUTHORS' CONCLUSIONS: There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain.


Assuntos
Episiotomia , Hipotermia Induzida/métodos , Manejo da Dor , Períneo/lesões , Terapia Combinada/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Magnetismo/uso terapêutico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Rev. cir. infant ; 12(2): 98-100, jun. 2002. ilus
Artigo em Espanhol | LILACS | ID: lil-321184

RESUMO

La medición de presiones en el canal anal y su comportamiento frente a la distensión artificial del recto(EMARS)se utiliza en el estudio del paciente constipado crónico,con resultados que alcanzan hasta un 100 por ciento de precisión en el diagnóstico de enfermedad de Hirschprung(EH)sin embargo en recién nacidos la falla en el diagnóstico con este método alcanza un 26 por ciento en niños a término y 71 por ciento en niños pretérmino.En este estudio evaluamos la utilidad de EMARS en 10 pacientes menores de 60 días de vida con edad gestacional entre 34 y 40 semanas.En 9 se encontraron relajaciones reflejas del esfínter anal interno que descartan EH,en el restante se practicó biopsia rectal que mostró ausencia de células ganglionares corroborando el diagnóstico de EH.A pesar del escaso número de pacientes evaluados,estos resultados avalarían la utilización del método en recién nacidos,independientemente de la edad gestacional


Assuntos
Recém-Nascido , Canal Anal , Doença de Hirschsprung , Manometria , Reto , Pediatria
10.
Rev. cir. infant ; 12(2): 98-100, jun. 2002. ilus
Artigo em Espanhol | BINACIS | ID: bin-7231

RESUMO

La medición de presiones en el canal anal y su comportamiento frente a la distensión artificial del recto(EMARS)se utiliza en el estudio del paciente constipado crónico,con resultados que alcanzan hasta un 100 por ciento de precisión en el diagnóstico de enfermedad de Hirschprung(EH)sin embargo en recién nacidos la falla en el diagnóstico con este método alcanza un 26 por ciento en niños a término y 71 por ciento en niños pretérmino.En este estudio evaluamos la utilidad de EMARS en 10 pacientes menores de 60 días de vida con edad gestacional entre 34 y 40 semanas.En 9 se encontraron relajaciones reflejas del esfínter anal interno que descartan EH,en el restante se practicó biopsia rectal que mostró ausencia de células ganglionares corroborando el diagnóstico de EH.A pesar del escaso número de pacientes evaluados,estos resultados avalarían la utilización del método en recién nacidos,independientemente de la edad gestacional


Assuntos
Recém-Nascido , Manometria , Canal Anal , Reto , Doença de Hirschsprung , Pediatria
12.
Midwifery ; 16(1): 48-55, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11139861

RESUMO

OBJECTIVE: To evaluate the effectiveness of standard regimes (ice packs and Epifoam) at relieving perineal trauma and compare these with a new cooling device (maternity gel pad). DESIGN: A randomised controlled trial involving three treatment groups. The women were free to choose the time of initial application (within four hours after delivery) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing. SETTING: A midwifery unit in the north of England and then continued in the women's own homes. PARTICIPANTS: 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward. MEASUREMENTS AND FINDINGS: The ordinal scale of none, mild, moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment (less than 4 hours), 24 hours and at 48 hours, by use of a newly developed visual evaluating tool. Self-assessed pain was recorded using a 10-point visual analogue scale within four hours, at 24 hours, 48 hours, and finally at five days after suturing. Women's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories; poor, fair, good, very good and excellent. A high proportion of women had some perineal oedema at initial assessment. A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours (p = 0.01), which was in favour of the maternity gel pad group. This was particularly noticeable for women with initial levels of mild oedema (p = 0.017). Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain (p = 0.048). A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment, through 24 hours to 48 hours (p < 0.0005). The bruising was significantly less in the gel-pad group in women who initially had no bruising (p = 0.021). There was no statistically significant effect of treatment at other initial levels of severity for oedema, bruising or pain at 24 hours, 48 hours and five days (for pain). Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups (p < 0.0005). KEY CONCLUSIONS: This trial demonstrated that a high proportion of women experience perineal oedema, bruising and pain following an instrumental delivery, which continues for at least five days for perineal pain, despite oral analgesia. Maternity gel pads, which were specially designed to cool the perineal region, were more effective in alleviating perineal trauma when compared with hospital standard regimens and were more highly rated by women.


Assuntos
Crioterapia , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapêutico , Gelo , Períneo/lesões , Complicações na Gravidez/terapia , Adulto , Contusões/terapia , Edema/terapia , Feminino , Géis/uso terapêutico , Humanos , Trabalho de Parto , Tocologia/métodos , Período Pós-Parto , Gravidez
13.
Arch Dis Child ; 80(6): 500-6, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10331996

RESUMO

AIMS: To determine whether home intervention by a specialist health visitor affects the outcome of children with failure to thrive. METHODS: Children referred for failure to thrive were randomised to receive conventional care, or conventional care and additional specialist home visiting for 12 months. Outcomes measured were growth, diet, use of health care resources, and Bayley, HAD (hospital anxiety and depression), and behavioural scales. RESULTS: Eighty three children, aged 4-30 months, were enrolled, 42 received specialist health visitor intervention. Children in both groups showed good weight gain (mean (SD) increase in weight SD score for the specialist health visitor intervention group 0.59 (0.63) v 0.42 (0.62) for the control group). Children < 12 months in the intervention group showed a higher mean (SD) increase in weight SD score than the control group (0.82 (0.86) v 0.42 (0.79)). Both groups improved in developmental score and energy intake. No significant differences were found for the primary outcome measures, but controls had significantly more dietary referrals, social service involvement, and hospital admissions, and were less compliant with appointments. CONCLUSIONS: The study failed to show that specialist health visitor intervention conferred additional benefits for the child. However, the specialist health visitor did provide a more coordinated approach, with significant savings in terms of health service use. Problems inherent to health service research are discussed.


Assuntos
Enfermagem em Saúde Comunitária , Insuficiência de Crescimento/enfermagem , Comportamento Infantil , Desenvolvimento Infantil , Serviços de Saúde da Criança/estatística & dados numéricos , Filho de Pais com Deficiência , Pré-Escolar , Dieta , Inglaterra , Feminino , Seguimentos , Crescimento , Humanos , Lactente , Masculino , Mães/psicologia , Pacientes Desistentes do Tratamento , Encaminhamento e Consulta , Análise de Regressão , Método Simples-Cego
16.
17.
Nephron ; 71(1): 16-22, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8538843

RESUMO

Undernutrition in dialysis patients contributes to their morbidity and mortality. This is a cross-sectional study of the nutritional status of 61 patients treated with continuous ambulatory peritoneal dialysis (CAPD). They were studied with emphasis on assessment of their nutritional intake, anthropometric measurements, and evaluation of biochemical parameters. The correlation between the rate of CAPD peritonitis and these measurements was also examined. The majority of the patients (63.1%) had inadequate protein intake ( < or = 1.2 g/kg/day). A comparable percentage had a low energy intake ( < or = 30 kcal/kg/day). Moderate malnutrition, as assessed by a low triceps skinfold thickness (TST) or a reduced midarm muscle circumference (MAMC) of < or = 20th percentile, was detected in 52% and 39% of the patients, respectively. Severe malnutrition (TST or MAMC < or = 10th percentile) was present in 36% of the patients. The serum insulin-like growth factor I (IGF-I) proved to be the most useful biochemical marker of malnutrition. It showed a positive correlation with TST (r = 0.325; p < 0.05). No significant correlation was observed with other short-life proteins such a transferrin or prealbumin. However, stepwise regression analysis showed the predictive value of serum IGF-I for anthropometric values to be low (adjusted R2 = 34.6%). Wasted patients did not appear to have more infections when compared to their healthier counterparts. However, a weak correlation was observed between TST and the number of peritonitis episodes.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Estado Nutricional/fisiologia , Diálise Peritoneal Ambulatorial Contínua , Peritonite/terapia , Antropometria , Estudos Transversais , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Peritonite/metabolismo , Dobras Cutâneas , Inquéritos e Questionários
18.
Rev Med Chil ; 119(12): 1372-80, 1991 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-9723093

RESUMO

The Washington Psychosocial Seizure Inventory (WPSI) was used in the assessment of psychosocial functioning of epileptic subjects in Chile. A total sample of 116 outpatients coming form an Epilepsy Program at a Public Health Service was evaluated. Disturbances in several areas relevant to psychosocial adjustment were noted. Their distribution was similar to that previously reported using the WPSI, although a greater severity of disturbances was noted. Peak score scales were financial status, emotional and interpersonal adjustment and overall psychosocial functioning. Rehabilitation measures could play a substantial role in the prevention and treatment of psychosocial disorders in epilepsy.


Assuntos
Adaptação Psicológica , Epilepsia/psicologia , Adolescente , Adulto , Idoso , Chile , Epilepsia/complicações , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos
19.
Arch Biochem Biophys ; 273(1): 128-36, 1989 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-2757387

RESUMO

The inhibitory effects of 7-[N-(3-aminopropyl)amino]heptan-2-one (APAH) on N8-acetylspermidine deacetylation were studied. In in vitro studies, APAH produced inhibition (apparent Ki of 0.18 microM) of N8-acetylspermidine deacetylation by the 100,000g supernatant fraction of rat liver. This apparent Ki was 60-fold less than the apparent Km (11 microM) for deacetylation of the substrate, N8-acetylspermidine, suggesting that APAH could be a potent, effective inhibitor in vivo. APAH was administered to mice by intraperitoneal injection at a dose of 200 mg/kg, and polyamine and acetylpolyamine levels in liver and spleen were measured. In tissues of control mice, N8-acetylspermidine was not detectable but increased to detectable levels 30-360 min after APAH treatment. These data are consistent with inhibition of the deacetylase by APAH. Increases in putrescine and N1-acetylspermidine levels occurred in liver after APAH treatment with increases in N1-acetylspermidine levels observed in spleen. In HeLa cells, a significant increase in N8-acetylspermidine was observed following 24 h exposure to 10 microM APAH while no change occurred in the acetylation level of HeLa cell histones. In contrast, 24 h exposure to 10 mM sodium butyrate produced no change in N8-acetylspermidine levels and an increase in the acetylation level of histones H4 and H2B. These results suggest that APAH has a relatively selective inhibitory effect on N8-acetylspermidine but not histone deacetylation. This is the first report of significant levels of N8-acetylspermidine in animal tissues and of the effects of in vivo inhibition of N8-acetylspermidine deacetylase.


Assuntos
Amidoidrolases/antagonistas & inibidores , Diaminas/farmacologia , Histonas/metabolismo , Espermidina/análogos & derivados , Acetilação , Amidoidrolases/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Densitometria , Diaminas/toxicidade , Células HeLa , Humanos , Fígado/análise , Fígado/enzimologia , Masculino , Camundongos , Putrescina/análise , Espermidina/análise , Espermidina/metabolismo , Baço/análise , Baço/enzimologia
20.
J Med Chem ; 32(5): 984-9, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2709384

RESUMO

Analogues of N8-acetylspermidine (1) were synthesized as potential inhibitors of the cytoplasmic enzyme N8-acetylspermidine deacetylase. The compounds were assayed for their ability to inhibit the deacetylation of 1 in a cytosolic fraction from rat liver. The apparent Ki values were determined by Dixon plots. The apparent Km of 1 for this enzyme is 11.0 microM. It was found that compounds which lacked the N1 or the N4 of spermidine were less effective at competing for the enzyme than the substrate. All compounds with acyl substituents larger than acetyl were less potent inhibitors than the corresponding acetylated derivatives. Thus, the enzyme's selectivity as a deacetylase seems to be attributable to steric hindrance which occurs with larger acyl groups. The N8 of the substrate is not essential for its binding to the enzyme. Replacement of N8 with a CH2 group gives the ketone 14, which has an apparent Ki of 0.18 microM, 60-fold lower than the apparent Km of 1. The inhibitory potency of 14 is retained in compounds substituted at the N1 position. The N1,N1-dimethyl and the N1,N1-diethyl analogues (15 and 16) of 14 have apparent Ki values of 0.096 and 0.10 microM, respectively. These agents are the most potent inhibitors of N8-acetylspermidine deacetylase reported, and they are promising tools for use in determining the physiological function of N8-acetylspermidine deacetylation.


Assuntos
Amidoidrolases/antagonistas & inibidores , Espermidina/análogos & derivados , Animais , Sítios de Ligação , Desenho de Fármacos , Masculino , Ratos , Ratos Endogâmicos , Espermidina/síntese química , Espermidina/farmacologia , Relação Estrutura-Atividade
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